Image Quizzes

The diagnosis is squamous cell carcinoma. A central or hilar mass is most likely to be a squamous cell carcinoma or a small cell tumor and less commonly an adenocarcinoma. Histologically, when there is lack of cohesion among the epithelial cells due to malignant changes, the cells get arranged in a concentric manner. The fate of a squamous cell is to form keratin, so these cells lay down keratin in a concentric manner and then appear as keratin pearls. 

This patient's tumor is found to have programmed cell death–ligand 1 ≥ 1% and has no actionable molecular markers. The patient has a performance status score of 1. In a patient with advanced or metastatic squamous cell carcinoma with a performance status score of 1, the National Comprehensive Cancer Network recommends pembrolizumab/carboplatin/paclitaxel or pembrolizumab/carboplatin/albumin-bound paclitaxel as preferred regimens. The pembrolizumab component is based on the results of the KEYNOTE-407 trial. In patients with previously untreated metastatic, squamous non-small cell lung cancer, the addition of pembrolizumab to chemotherapy with carboplatin plus paclitaxel or nab-paclitaxel resulted in significantly longer overall survival and progression-free survival than chemotherapy alone.

Maurie Markman, MD, President, Department of Medical Oncology, Cancer Treatment Centers of America.

Maurie Markman, MD, has disclosed the following relevant financial relationships:

Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: Merck
Serve(d) as a speaker or a member of a speakers bureau for: AstraZeneca; Novis; Glaxo Smith Kline
Received research grant from: AstraZeneca; Novis; GSK; Merck

The diagnosis is squamous cell carcinoma. A central or hilar mass is most likely to be a squamous cell carcinoma or a small cell tumor and less commonly an adenocarcinoma. Histologically, when there is lack of cohesion among the epithelial cells due to malignant changes, the cells get arranged in a concentric manner. The fate of a squamous cell is to form keratin, so these cells lay down keratin in a concentric manner and then appear as keratin pearls. 

This patient's tumor is found to have programmed cell death–ligand 1 ≥ 1% and has no actionable molecular markers. The patient has a performance status score of 1. In a patient with advanced or metastatic squamous cell carcinoma with a performance status score of 1, the National Comprehensive Cancer Network recommends pembrolizumab/carboplatin/paclitaxel or pembrolizumab/carboplatin/albumin-bound paclitaxel as preferred regimens. The pembrolizumab component is based on the results of the KEYNOTE-407 trial. In patients with previously untreated metastatic, squamous non-small cell lung cancer, the addition of pembrolizumab to chemotherapy with carboplatin plus paclitaxel or nab-paclitaxel resulted in significantly longer overall survival and progression-free survival than chemotherapy alone.

Maurie Markman, MD, President, Department of Medical Oncology, Cancer Treatment Centers of America.

Maurie Markman, MD, has disclosed the following relevant financial relationships:

Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: Merck
Serve(d) as a speaker or a member of a speakers bureau for: AstraZeneca; Novis; Glaxo Smith Kline
Received research grant from: AstraZeneca; Novis; GSK; Merck

The diagnosis is squamous cell carcinoma. A central or hilar mass is most likely to be a squamous cell carcinoma or a small cell tumor and less commonly an adenocarcinoma. Histologically, when there is lack of cohesion among the epithelial cells due to malignant changes, the cells get arranged in a concentric manner. The fate of a squamous cell is to form keratin, so these cells lay down keratin in a concentric manner and then appear as keratin pearls. 

This patient's tumor is found to have programmed cell death–ligand 1 ≥ 1% and has no actionable molecular markers. The patient has a performance status score of 1. In a patient with advanced or metastatic squamous cell carcinoma with a performance status score of 1, the National Comprehensive Cancer Network recommends pembrolizumab/carboplatin/paclitaxel or pembrolizumab/carboplatin/albumin-bound paclitaxel as preferred regimens. The pembrolizumab component is based on the results of the KEYNOTE-407 trial. In patients with previously untreated metastatic, squamous non-small cell lung cancer, the addition of pembrolizumab to chemotherapy with carboplatin plus paclitaxel or nab-paclitaxel resulted in significantly longer overall survival and progression-free survival than chemotherapy alone.

Maurie Markman, MD, President, Department of Medical Oncology, Cancer Treatment Centers of America.

Maurie Markman, MD, has disclosed the following relevant financial relationships:

Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: Merck
Serve(d) as a speaker or a member of a speakers bureau for: AstraZeneca; Novis; Glaxo Smith Kline
Received research grant from: AstraZeneca; Novis; GSK; Merck

It is likely that the polypoid appearance of the colonic lining is a result of chronic inflammation of longstanding Crohn disease with an ileocolonic manifestation. Crohn disease is an idiopathic, chronic inflammatory bowel disease characterized by cycles of relapse and remission. These asymptomatic periods can last for several months up to a few years, as reported by the patient in this case. Up to 50% of cases of Crohn disease are characterized by ileocolitis, or inflammation of the ileum and the colon. Although postinflammatory polyps are a cancer risk factor for inflammatory bowel disease and pseudopolyps are associated with severe disease, their appearance is not necessarily a poor prognostic factor.

When assessing ongoing disease activity in ileocolonic Crohn disease or ulcerative colitis, colonoscopy represents the first-line approach. Endoscopic visualization and biopsy are critical components of the diagnosis. Alternatively, cross-sectional imaging can be used to assess disease phenotype. In addition, plain radiography or a CT scan of the abdomen can identify bowel obstruction and scanning of the pelvis can detect any intra-abdominal abscesses. Ulcerative colitis looms large in the differential diagnosis. Although weight loss, perineal disease, fistulae, and obstruction are common in Crohn disease, they are uncommon or rare in ulcerative colitis, although bleeding is observed much more frequently in ulcerative colitis. 

Treatment of Crohn disease is based on the severity, location, and subtype (inflammatory, stricturing, or penetrating). There is also now a focus on determining which patients are at risk for a more severe disease course and may require earlier and more aggressive therapies. Crohn disease is primarily managed through the introduction of early immunosuppressive or combination therapy with biologic agents in high-risk patients, as well as complementary diet modification. Although most patients will ultimately undergo surgery, there is no curative approach, unlike in ulcerative colitis.

In its clinical care pathway, the American Gastroenterological Association supports a top-down approach to therapy for adult patients with moderate to severe luminal Crohn disease (defining moderate to severe disease as having a Crohn Disease Activity Index score of 220 or higher, or having a high risk of complications). This approach supports the early use of biologic agents, with or without immunomodulators, over a stepwise strategy. The patient’s response to this new regimen should be determined in the 12-week period after the initiation of therapy. Endoscopy or transmural responses to therapy should be assessed after 6 months.

Bhupinder S. Anand, MD, Professor, Department of Medicine, Baylor College of Medicine, Houston, TX

Bhupinder S. Anand, MD, has disclosed no relevant financial relationships.

It is likely that the polypoid appearance of the colonic lining is a result of chronic inflammation of longstanding Crohn disease with an ileocolonic manifestation. Crohn disease is an idiopathic, chronic inflammatory bowel disease characterized by cycles of relapse and remission. These asymptomatic periods can last for several months up to a few years, as reported by the patient in this case. Up to 50% of cases of Crohn disease are characterized by ileocolitis, or inflammation of the ileum and the colon. Although postinflammatory polyps are a cancer risk factor for inflammatory bowel disease and pseudopolyps are associated with severe disease, their appearance is not necessarily a poor prognostic factor.

When assessing ongoing disease activity in ileocolonic Crohn disease or ulcerative colitis, colonoscopy represents the first-line approach. Endoscopic visualization and biopsy are critical components of the diagnosis. Alternatively, cross-sectional imaging can be used to assess disease phenotype. In addition, plain radiography or a CT scan of the abdomen can identify bowel obstruction and scanning of the pelvis can detect any intra-abdominal abscesses. Ulcerative colitis looms large in the differential diagnosis. Although weight loss, perineal disease, fistulae, and obstruction are common in Crohn disease, they are uncommon or rare in ulcerative colitis, although bleeding is observed much more frequently in ulcerative colitis. 

Treatment of Crohn disease is based on the severity, location, and subtype (inflammatory, stricturing, or penetrating). There is also now a focus on determining which patients are at risk for a more severe disease course and may require earlier and more aggressive therapies. Crohn disease is primarily managed through the introduction of early immunosuppressive or combination therapy with biologic agents in high-risk patients, as well as complementary diet modification. Although most patients will ultimately undergo surgery, there is no curative approach, unlike in ulcerative colitis.

In its clinical care pathway, the American Gastroenterological Association supports a top-down approach to therapy for adult patients with moderate to severe luminal Crohn disease (defining moderate to severe disease as having a Crohn Disease Activity Index score of 220 or higher, or having a high risk of complications). This approach supports the early use of biologic agents, with or without immunomodulators, over a stepwise strategy. The patient’s response to this new regimen should be determined in the 12-week period after the initiation of therapy. Endoscopy or transmural responses to therapy should be assessed after 6 months.

Bhupinder S. Anand, MD, Professor, Department of Medicine, Baylor College of Medicine, Houston, TX

Bhupinder S. Anand, MD, has disclosed no relevant financial relationships.

It is likely that the polypoid appearance of the colonic lining is a result of chronic inflammation of longstanding Crohn disease with an ileocolonic manifestation. Crohn disease is an idiopathic, chronic inflammatory bowel disease characterized by cycles of relapse and remission. These asymptomatic periods can last for several months up to a few years, as reported by the patient in this case. Up to 50% of cases of Crohn disease are characterized by ileocolitis, or inflammation of the ileum and the colon. Although postinflammatory polyps are a cancer risk factor for inflammatory bowel disease and pseudopolyps are associated with severe disease, their appearance is not necessarily a poor prognostic factor.

When assessing ongoing disease activity in ileocolonic Crohn disease or ulcerative colitis, colonoscopy represents the first-line approach. Endoscopic visualization and biopsy are critical components of the diagnosis. Alternatively, cross-sectional imaging can be used to assess disease phenotype. In addition, plain radiography or a CT scan of the abdomen can identify bowel obstruction and scanning of the pelvis can detect any intra-abdominal abscesses. Ulcerative colitis looms large in the differential diagnosis. Although weight loss, perineal disease, fistulae, and obstruction are common in Crohn disease, they are uncommon or rare in ulcerative colitis, although bleeding is observed much more frequently in ulcerative colitis. 

Treatment of Crohn disease is based on the severity, location, and subtype (inflammatory, stricturing, or penetrating). There is also now a focus on determining which patients are at risk for a more severe disease course and may require earlier and more aggressive therapies. Crohn disease is primarily managed through the introduction of early immunosuppressive or combination therapy with biologic agents in high-risk patients, as well as complementary diet modification. Although most patients will ultimately undergo surgery, there is no curative approach, unlike in ulcerative colitis.

In its clinical care pathway, the American Gastroenterological Association supports a top-down approach to therapy for adult patients with moderate to severe luminal Crohn disease (defining moderate to severe disease as having a Crohn Disease Activity Index score of 220 or higher, or having a high risk of complications). This approach supports the early use of biologic agents, with or without immunomodulators, over a stepwise strategy. The patient’s response to this new regimen should be determined in the 12-week period after the initiation of therapy. Endoscopy or transmural responses to therapy should be assessed after 6 months.

Bhupinder S. Anand, MD, Professor, Department of Medicine, Baylor College of Medicine, Houston, TX

Bhupinder S. Anand, MD, has disclosed no relevant financial relationships.

The differential diagnosis of inflammatory bowel disease (IBD) in older patients is complicated by comorbid conditions such as infectious colitis, segmental colitis associated with diverticular disease, nonsteroidal anti-inflammatory drug-induced intestinal injury, and ischemia, each of which can mimic the intestinal inflammation characteristic of IBD. 

Ulcerative colitis is one of the two major types of IBD, along with Crohn disease. Unlike Crohn disease, which can affect any part of the gastrointestinal tract, ulcerative colitis characteristically causes inflammation in the large bowel (see image). 

Acute, severe ulcerative colitis (ie, > six bloody bowel movements per day, with one of the following: temperature > 38 °C [100.4 °F], hemoglobin level < 10.5 g/dL, heart rate > 90 beats/min, erythrocyte sedimentation rate > 30 mm/hr, or C-reactive protein level > 30 mg/dL) requires hospitalization and treatment with intravenous high-dose corticosteroids (hydrocortisone 400 mg/day or methylprednisolone 60 mg/day). 

The diagnosis of ulcerative colitis is best made with endoscopy and mucosal biopsy for histopathologic analysis. Characteristic findings are abnormal erythematous mucosa, with or without ulceration, extending from the rectum to a part or all of the colon; and uniform inflammation without intervening areas of normal mucosa (skip lesions tend to be characteristic of Crohn disease). Contact bleeding may also be observed, with mucus identified in the lumen of the bowel.

The bowel wall in a patient with ulcerative colitis is thin or of normal thickness, but edema, the accumulation of fat, and hypertrophy of the muscle layer may give the impression of a thickened bowel wall. The disease is largely confined to the mucosa and, to a lesser extent, the submucosa.

Laboratory studies are helpful to exclude other diagnoses and assess the patient's nutritional status, but serologic markers can help in the differential diagnosis of IBD. Radiographic imaging has an important role in the workup of patients with suspected IBD and in the differentiation of ulcerative colitis from Crohn disease by demonstrating fistulae or the presence of small bowel disease seen only in Crohn disease.

Much work in the past decade has focused on the development of serologic markers for inflammatory bowel disease. pANCA and anti–Saccharomyces cerevisiae antibodies (ASCA) have been the most intensely studied. The World Gastroenterology Organization states that ulcerative colitis is more likely when the test results are positive for pANCA and negative for ASCA antigen; however, the pANCA test result may be positive in patients with Crohn disease, and this may complicate obtaining a diagnosis in an otherwise uncomplicated colitis.

According to the American Gastroenterological Association, drug classes for the long-term management of moderate to severe ulcerative colitis include tumor necrosis factor-alpha antagonists, anti-integrin agent (vedolizumab), Janus kinase inhibitor (tofacitinib), interleukin-12/23 antagonist (ustekinumab), and immunomodulators (thiopurines, methotrexate). In general, most drugs that are initiated for the induction of remission are continued as maintenance therapy if they are effective.

Bhupinder S. Anand, MD, Professor, Department of Medicine, Baylor College of Medicine, Houston, TX

Bhupinder S. Anand, MD, has disclosed no relevant financial relationships.

The differential diagnosis of inflammatory bowel disease (IBD) in older patients is complicated by comorbid conditions such as infectious colitis, segmental colitis associated with diverticular disease, nonsteroidal anti-inflammatory drug-induced intestinal injury, and ischemia, each of which can mimic the intestinal inflammation characteristic of IBD. 

Ulcerative colitis is one of the two major types of IBD, along with Crohn disease. Unlike Crohn disease, which can affect any part of the gastrointestinal tract, ulcerative colitis characteristically causes inflammation in the large bowel (see image). 

Acute, severe ulcerative colitis (ie, > six bloody bowel movements per day, with one of the following: temperature > 38 °C [100.4 °F], hemoglobin level < 10.5 g/dL, heart rate > 90 beats/min, erythrocyte sedimentation rate > 30 mm/hr, or C-reactive protein level > 30 mg/dL) requires hospitalization and treatment with intravenous high-dose corticosteroids (hydrocortisone 400 mg/day or methylprednisolone 60 mg/day). 

The diagnosis of ulcerative colitis is best made with endoscopy and mucosal biopsy for histopathologic analysis. Characteristic findings are abnormal erythematous mucosa, with or without ulceration, extending from the rectum to a part or all of the colon; and uniform inflammation without intervening areas of normal mucosa (skip lesions tend to be characteristic of Crohn disease). Contact bleeding may also be observed, with mucus identified in the lumen of the bowel.

The bowel wall in a patient with ulcerative colitis is thin or of normal thickness, but edema, the accumulation of fat, and hypertrophy of the muscle layer may give the impression of a thickened bowel wall. The disease is largely confined to the mucosa and, to a lesser extent, the submucosa.

Laboratory studies are helpful to exclude other diagnoses and assess the patient's nutritional status, but serologic markers can help in the differential diagnosis of IBD. Radiographic imaging has an important role in the workup of patients with suspected IBD and in the differentiation of ulcerative colitis from Crohn disease by demonstrating fistulae or the presence of small bowel disease seen only in Crohn disease.

Much work in the past decade has focused on the development of serologic markers for inflammatory bowel disease. pANCA and anti–Saccharomyces cerevisiae antibodies (ASCA) have been the most intensely studied. The World Gastroenterology Organization states that ulcerative colitis is more likely when the test results are positive for pANCA and negative for ASCA antigen; however, the pANCA test result may be positive in patients with Crohn disease, and this may complicate obtaining a diagnosis in an otherwise uncomplicated colitis.

According to the American Gastroenterological Association, drug classes for the long-term management of moderate to severe ulcerative colitis include tumor necrosis factor-alpha antagonists, anti-integrin agent (vedolizumab), Janus kinase inhibitor (tofacitinib), interleukin-12/23 antagonist (ustekinumab), and immunomodulators (thiopurines, methotrexate). In general, most drugs that are initiated for the induction of remission are continued as maintenance therapy if they are effective.

Bhupinder S. Anand, MD, Professor, Department of Medicine, Baylor College of Medicine, Houston, TX

Bhupinder S. Anand, MD, has disclosed no relevant financial relationships.

The differential diagnosis of inflammatory bowel disease (IBD) in older patients is complicated by comorbid conditions such as infectious colitis, segmental colitis associated with diverticular disease, nonsteroidal anti-inflammatory drug-induced intestinal injury, and ischemia, each of which can mimic the intestinal inflammation characteristic of IBD. 

Ulcerative colitis is one of the two major types of IBD, along with Crohn disease. Unlike Crohn disease, which can affect any part of the gastrointestinal tract, ulcerative colitis characteristically causes inflammation in the large bowel (see image). 

Acute, severe ulcerative colitis (ie, > six bloody bowel movements per day, with one of the following: temperature > 38 °C [100.4 °F], hemoglobin level < 10.5 g/dL, heart rate > 90 beats/min, erythrocyte sedimentation rate > 30 mm/hr, or C-reactive protein level > 30 mg/dL) requires hospitalization and treatment with intravenous high-dose corticosteroids (hydrocortisone 400 mg/day or methylprednisolone 60 mg/day). 

The diagnosis of ulcerative colitis is best made with endoscopy and mucosal biopsy for histopathologic analysis. Characteristic findings are abnormal erythematous mucosa, with or without ulceration, extending from the rectum to a part or all of the colon; and uniform inflammation without intervening areas of normal mucosa (skip lesions tend to be characteristic of Crohn disease). Contact bleeding may also be observed, with mucus identified in the lumen of the bowel.

The bowel wall in a patient with ulcerative colitis is thin or of normal thickness, but edema, the accumulation of fat, and hypertrophy of the muscle layer may give the impression of a thickened bowel wall. The disease is largely confined to the mucosa and, to a lesser extent, the submucosa.

Laboratory studies are helpful to exclude other diagnoses and assess the patient's nutritional status, but serologic markers can help in the differential diagnosis of IBD. Radiographic imaging has an important role in the workup of patients with suspected IBD and in the differentiation of ulcerative colitis from Crohn disease by demonstrating fistulae or the presence of small bowel disease seen only in Crohn disease.

Much work in the past decade has focused on the development of serologic markers for inflammatory bowel disease. pANCA and anti–Saccharomyces cerevisiae antibodies (ASCA) have been the most intensely studied. The World Gastroenterology Organization states that ulcerative colitis is more likely when the test results are positive for pANCA and negative for ASCA antigen; however, the pANCA test result may be positive in patients with Crohn disease, and this may complicate obtaining a diagnosis in an otherwise uncomplicated colitis.

According to the American Gastroenterological Association, drug classes for the long-term management of moderate to severe ulcerative colitis include tumor necrosis factor-alpha antagonists, anti-integrin agent (vedolizumab), Janus kinase inhibitor (tofacitinib), interleukin-12/23 antagonist (ustekinumab), and immunomodulators (thiopurines, methotrexate). In general, most drugs that are initiated for the induction of remission are continued as maintenance therapy if they are effective.

Bhupinder S. Anand, MD, Professor, Department of Medicine, Baylor College of Medicine, Houston, TX

Bhupinder S. Anand, MD, has disclosed no relevant financial relationships.

Carcinomas like prostate cancer possess notable bony tropism and can metastasize to the lumbar‐sacral spine and pelvis, draining through the pelvic plexus of the lumbar region. Approximately 90% of patients with advanced prostate cancer develop bone metastasis, the spine being the most common site. Manifestations of metastatic prostate cancer include weight loss and loss of appetite; bone pain, with or without pathologic fracture; and lower-extremity pain and edema. Urinary symptoms are also common. Other physical examination findings are adenopathy, bony tenderness, and lower-extremity edema, as seen in the present case.

Radiologic findings of bone metastases can mimic Paget disease, and even though bone metastases are blastic, lytic lesions may develop and cause pathologic fractures. Such fractures must be distinguished from osteoporotic fractures that can occur after prolonged luteinizing hormone–releasing hormone therapy. Also included in the differential of the present case are lymphomas, which can manifest as pelvic masses and bone lesions and have been reported with prostate cancer. However, considering the patient's history, physical examination, and lab results, bone metastasis is the most likely diagnosis.

Bone imaging should be performed for any patient with suspected bone metastases; specifically, multiparametric MRI outperforms bone scan and targeted x-rays for detection of bone metastases. Because activity in the bone scan may not be observed until 5 years after micrometastasis has occurred, negative bone scan results cannot be used to definitively exclude metastasis. 

The alpha emitter radium-223 is a category 1 option to treat symptomatic bone metastases (but should not be used in patients with visceral metastases). It is not recommended for use in combination with docetaxel or any other systemic therapy but may be used with androgen-deprivation therapy (ADT), as studies have suggested that the addition of ADT improves progression-free survival in patients with castrate-resistant prostate cancer with metastasis. Concomitant use of denosumab or zoledronic acid is also recommended. 

Kyle A. Richards, MD, Assistant Professor, Department of Urology, University of Wisconsin-Madison; Chief of Urology, William S. Middleton Memorial VA Hospital, Madison, Wisconsin

Kyle A. Richards, MD, has disclosed no relevant financial relationships

Carcinomas like prostate cancer possess notable bony tropism and can metastasize to the lumbar‐sacral spine and pelvis, draining through the pelvic plexus of the lumbar region. Approximately 90% of patients with advanced prostate cancer develop bone metastasis, the spine being the most common site. Manifestations of metastatic prostate cancer include weight loss and loss of appetite; bone pain, with or without pathologic fracture; and lower-extremity pain and edema. Urinary symptoms are also common. Other physical examination findings are adenopathy, bony tenderness, and lower-extremity edema, as seen in the present case.

Radiologic findings of bone metastases can mimic Paget disease, and even though bone metastases are blastic, lytic lesions may develop and cause pathologic fractures. Such fractures must be distinguished from osteoporotic fractures that can occur after prolonged luteinizing hormone–releasing hormone therapy. Also included in the differential of the present case are lymphomas, which can manifest as pelvic masses and bone lesions and have been reported with prostate cancer. However, considering the patient's history, physical examination, and lab results, bone metastasis is the most likely diagnosis.

Bone imaging should be performed for any patient with suspected bone metastases; specifically, multiparametric MRI outperforms bone scan and targeted x-rays for detection of bone metastases. Because activity in the bone scan may not be observed until 5 years after micrometastasis has occurred, negative bone scan results cannot be used to definitively exclude metastasis. 

The alpha emitter radium-223 is a category 1 option to treat symptomatic bone metastases (but should not be used in patients with visceral metastases). It is not recommended for use in combination with docetaxel or any other systemic therapy but may be used with androgen-deprivation therapy (ADT), as studies have suggested that the addition of ADT improves progression-free survival in patients with castrate-resistant prostate cancer with metastasis. Concomitant use of denosumab or zoledronic acid is also recommended. 

Kyle A. Richards, MD, Assistant Professor, Department of Urology, University of Wisconsin-Madison; Chief of Urology, William S. Middleton Memorial VA Hospital, Madison, Wisconsin

Kyle A. Richards, MD, has disclosed no relevant financial relationships

Carcinomas like prostate cancer possess notable bony tropism and can metastasize to the lumbar‐sacral spine and pelvis, draining through the pelvic plexus of the lumbar region. Approximately 90% of patients with advanced prostate cancer develop bone metastasis, the spine being the most common site. Manifestations of metastatic prostate cancer include weight loss and loss of appetite; bone pain, with or without pathologic fracture; and lower-extremity pain and edema. Urinary symptoms are also common. Other physical examination findings are adenopathy, bony tenderness, and lower-extremity edema, as seen in the present case.

Radiologic findings of bone metastases can mimic Paget disease, and even though bone metastases are blastic, lytic lesions may develop and cause pathologic fractures. Such fractures must be distinguished from osteoporotic fractures that can occur after prolonged luteinizing hormone–releasing hormone therapy. Also included in the differential of the present case are lymphomas, which can manifest as pelvic masses and bone lesions and have been reported with prostate cancer. However, considering the patient's history, physical examination, and lab results, bone metastasis is the most likely diagnosis.

Bone imaging should be performed for any patient with suspected bone metastases; specifically, multiparametric MRI outperforms bone scan and targeted x-rays for detection of bone metastases. Because activity in the bone scan may not be observed until 5 years after micrometastasis has occurred, negative bone scan results cannot be used to definitively exclude metastasis. 

The alpha emitter radium-223 is a category 1 option to treat symptomatic bone metastases (but should not be used in patients with visceral metastases). It is not recommended for use in combination with docetaxel or any other systemic therapy but may be used with androgen-deprivation therapy (ADT), as studies have suggested that the addition of ADT improves progression-free survival in patients with castrate-resistant prostate cancer with metastasis. Concomitant use of denosumab or zoledronic acid is also recommended. 

Kyle A. Richards, MD, Assistant Professor, Department of Urology, University of Wisconsin-Madison; Chief of Urology, William S. Middleton Memorial VA Hospital, Madison, Wisconsin

Kyle A. Richards, MD, has disclosed no relevant financial relationships

This patient has the “atopic triad” of allergies, asthma, and atopic dermatitis. Atopic dermatitis around the eyes and on the eyelids often develops in teenage years and adulthood but may also occur in older persons. Occasionally, it can be the only manifestation of atopic dermatitis. The upper eyelids may appear scaly and fissured. The so-called "allergic shiners" (symmetric, dark circles beneath the lower eyelid) and Dennie-Morgan lines (extra skin folds under the lower eyelid) are often present.

The thin skin of the eyelids is particularly sensitive to irritants and allergens and is thus prone to develop dermatitis. Contact with the same trigger may not lead to a rash on other areas of skin. Upper, lower or both eyelids on one or both sides can be affected. The patient may report itching, stinging or burning, and the lids are red and scaly. They may swell. With persistence of the dermatitis, the eyelids become thickened with increased skin markings (lichenification). The eyelid margins may become involved (blepharitis). The appearance is similar, whatever the cause.

The basis of treatment for atopic dermatitis is to provide moisturization for dryness, allay pruritus, and manage inflammation of the eczematous lesions. Conservative initial management of eyelid dermatitis also includes gentle skin care and avoidance of fragrance and other known irritants in personal care, hair, and facial skin care products. Bland, fragrance-free emollients, such as petrolatum, may be applied directly to the eyelids.

Topical corticosteroids are one therapeutic option for eyelid dermatitis. However, only low-potency topical corticosteroids are safe, and only for short-term use, on the eyelids. Typically, they are used twice daily for 2-4 weeks. However, even with low-potency topical corticosteroids, the eyelids remain vulnerable to thinning, even atrophy. Because of these issues, topical calcineurin inhibitors are often the preferred treatment. 

Patients with atopic dermatitis have an increased risk of comorbid eye diseases, including keratitis, conjunctivitis, and keratoconus. A careful clinical examination for associated erythema, crusting, and blepharitis many prompt a referral to an ophthalmologist.

Brian S. Kim, MD, Associate Professor, Department of Medicine, Division of Dermatology, Washington University School of Medicine, St. Louis, Missouri

Brian S. Kim, MD, has disclosed no relevant financial relationships.

This patient has the “atopic triad” of allergies, asthma, and atopic dermatitis. Atopic dermatitis around the eyes and on the eyelids often develops in teenage years and adulthood but may also occur in older persons. Occasionally, it can be the only manifestation of atopic dermatitis. The upper eyelids may appear scaly and fissured. The so-called "allergic shiners" (symmetric, dark circles beneath the lower eyelid) and Dennie-Morgan lines (extra skin folds under the lower eyelid) are often present.

The thin skin of the eyelids is particularly sensitive to irritants and allergens and is thus prone to develop dermatitis. Contact with the same trigger may not lead to a rash on other areas of skin. Upper, lower or both eyelids on one or both sides can be affected. The patient may report itching, stinging or burning, and the lids are red and scaly. They may swell. With persistence of the dermatitis, the eyelids become thickened with increased skin markings (lichenification). The eyelid margins may become involved (blepharitis). The appearance is similar, whatever the cause.

The basis of treatment for atopic dermatitis is to provide moisturization for dryness, allay pruritus, and manage inflammation of the eczematous lesions. Conservative initial management of eyelid dermatitis also includes gentle skin care and avoidance of fragrance and other known irritants in personal care, hair, and facial skin care products. Bland, fragrance-free emollients, such as petrolatum, may be applied directly to the eyelids.

Topical corticosteroids are one therapeutic option for eyelid dermatitis. However, only low-potency topical corticosteroids are safe, and only for short-term use, on the eyelids. Typically, they are used twice daily for 2-4 weeks. However, even with low-potency topical corticosteroids, the eyelids remain vulnerable to thinning, even atrophy. Because of these issues, topical calcineurin inhibitors are often the preferred treatment. 

Patients with atopic dermatitis have an increased risk of comorbid eye diseases, including keratitis, conjunctivitis, and keratoconus. A careful clinical examination for associated erythema, crusting, and blepharitis many prompt a referral to an ophthalmologist.

Brian S. Kim, MD, Associate Professor, Department of Medicine, Division of Dermatology, Washington University School of Medicine, St. Louis, Missouri

Brian S. Kim, MD, has disclosed no relevant financial relationships.

This patient has the “atopic triad” of allergies, asthma, and atopic dermatitis. Atopic dermatitis around the eyes and on the eyelids often develops in teenage years and adulthood but may also occur in older persons. Occasionally, it can be the only manifestation of atopic dermatitis. The upper eyelids may appear scaly and fissured. The so-called "allergic shiners" (symmetric, dark circles beneath the lower eyelid) and Dennie-Morgan lines (extra skin folds under the lower eyelid) are often present.

The thin skin of the eyelids is particularly sensitive to irritants and allergens and is thus prone to develop dermatitis. Contact with the same trigger may not lead to a rash on other areas of skin. Upper, lower or both eyelids on one or both sides can be affected. The patient may report itching, stinging or burning, and the lids are red and scaly. They may swell. With persistence of the dermatitis, the eyelids become thickened with increased skin markings (lichenification). The eyelid margins may become involved (blepharitis). The appearance is similar, whatever the cause.

The basis of treatment for atopic dermatitis is to provide moisturization for dryness, allay pruritus, and manage inflammation of the eczematous lesions. Conservative initial management of eyelid dermatitis also includes gentle skin care and avoidance of fragrance and other known irritants in personal care, hair, and facial skin care products. Bland, fragrance-free emollients, such as petrolatum, may be applied directly to the eyelids.

Topical corticosteroids are one therapeutic option for eyelid dermatitis. However, only low-potency topical corticosteroids are safe, and only for short-term use, on the eyelids. Typically, they are used twice daily for 2-4 weeks. However, even with low-potency topical corticosteroids, the eyelids remain vulnerable to thinning, even atrophy. Because of these issues, topical calcineurin inhibitors are often the preferred treatment. 

Patients with atopic dermatitis have an increased risk of comorbid eye diseases, including keratitis, conjunctivitis, and keratoconus. A careful clinical examination for associated erythema, crusting, and blepharitis many prompt a referral to an ophthalmologist.

Brian S. Kim, MD, Associate Professor, Department of Medicine, Division of Dermatology, Washington University School of Medicine, St. Louis, Missouri

Brian S. Kim, MD, has disclosed no relevant financial relationships.

This young patient is probably presenting with pediatric multiple sclerosis (MS). It is estimated that MS onset before the age of 18 years accounts for 3%-5% of the general population of patients with this autoimmune disease. The condition represents the most common nontraumatic, disabling neurologic disorder among young adults. Disease prevalence is highest between the ages of 13 and 16. In children older than 10, a female predominance is seen, suggesting a hormonal role in pathogenesis. The vast majority (up to 98%) of children and adolescents with MS have a relapsing-remitting course. Overall, pediatric MS has a milder course than adult MS but can lead to significant disability at an early age. Although pediatric patients may experience more frequent relapses, data also suggest that children seem to recover more quickly from episodes than adults.

In children and adolescents, MS most typically manifests with sensory disturbances and impaired coordination. The most commonly reported symptoms in pediatric MS are sensory, motor, and brainstem dysfunction, though cognitive and emotional disorders can emerge over time.

Younger children will often show multifocal symptoms but with the onset of adolescence may begin to present with only a single focal symptom, as is often the case with adult patients.

Diagnosis of pediatric MS goes hand-in-hand with a diagnosis of clinically isolated syndrome (CIS) or sporadic acute disseminated encephalomyelitis (ADEM). CIS is diagnosed when symptoms last for over 24 hours with possible inflammatory demyelination but without encephalopathy. To confirm an MS diagnosis, two or more clinical episodes must occur at least 30 days apart. MRI can both confirm diagnosis and offer great value in monitoring disease progression in the brain and spinal cord. Of note, differentiating the first episode of juvenile MS from ADEM is a significant clinical challenge.

When it comes to treating relapses, the approach in children is similar to that of adults. Therapy may consist of an intravenous pulse of methylprednisolone (20-30 mg/kg/day for 3-5 days). In 2018, the FDA approved the use of the oral MS therapy Gilenya (fingolimod) for the treatment of patients 10 years of age or older with relapsing forms of MS. Providers can also adapt treatments approved for adults for pediatric patients. 

Krupa Pandey, MD, Director, Multiple Sclerosis Center, Department of Neurology & Neuroscience Institute, Hackensack University Medical Center; Neurologist, Department of Neurology, Hackensack Meridian Health, Hackensack, NJ

Krupa Pandey, MD, has serve(d) as a speaker or a member of a speakers bureau for: Bristol-Myers Squibb; Biogen; Alexion; Genentech; Sanofi-Genzyme

This young patient is probably presenting with pediatric multiple sclerosis (MS). It is estimated that MS onset before the age of 18 years accounts for 3%-5% of the general population of patients with this autoimmune disease. The condition represents the most common nontraumatic, disabling neurologic disorder among young adults. Disease prevalence is highest between the ages of 13 and 16. In children older than 10, a female predominance is seen, suggesting a hormonal role in pathogenesis. The vast majority (up to 98%) of children and adolescents with MS have a relapsing-remitting course. Overall, pediatric MS has a milder course than adult MS but can lead to significant disability at an early age. Although pediatric patients may experience more frequent relapses, data also suggest that children seem to recover more quickly from episodes than adults.

In children and adolescents, MS most typically manifests with sensory disturbances and impaired coordination. The most commonly reported symptoms in pediatric MS are sensory, motor, and brainstem dysfunction, though cognitive and emotional disorders can emerge over time.

Younger children will often show multifocal symptoms but with the onset of adolescence may begin to present with only a single focal symptom, as is often the case with adult patients.

Diagnosis of pediatric MS goes hand-in-hand with a diagnosis of clinically isolated syndrome (CIS) or sporadic acute disseminated encephalomyelitis (ADEM). CIS is diagnosed when symptoms last for over 24 hours with possible inflammatory demyelination but without encephalopathy. To confirm an MS diagnosis, two or more clinical episodes must occur at least 30 days apart. MRI can both confirm diagnosis and offer great value in monitoring disease progression in the brain and spinal cord. Of note, differentiating the first episode of juvenile MS from ADEM is a significant clinical challenge.

When it comes to treating relapses, the approach in children is similar to that of adults. Therapy may consist of an intravenous pulse of methylprednisolone (20-30 mg/kg/day for 3-5 days). In 2018, the FDA approved the use of the oral MS therapy Gilenya (fingolimod) for the treatment of patients 10 years of age or older with relapsing forms of MS. Providers can also adapt treatments approved for adults for pediatric patients. 

Krupa Pandey, MD, Director, Multiple Sclerosis Center, Department of Neurology & Neuroscience Institute, Hackensack University Medical Center; Neurologist, Department of Neurology, Hackensack Meridian Health, Hackensack, NJ

Krupa Pandey, MD, has serve(d) as a speaker or a member of a speakers bureau for: Bristol-Myers Squibb; Biogen; Alexion; Genentech; Sanofi-Genzyme

This young patient is probably presenting with pediatric multiple sclerosis (MS). It is estimated that MS onset before the age of 18 years accounts for 3%-5% of the general population of patients with this autoimmune disease. The condition represents the most common nontraumatic, disabling neurologic disorder among young adults. Disease prevalence is highest between the ages of 13 and 16. In children older than 10, a female predominance is seen, suggesting a hormonal role in pathogenesis. The vast majority (up to 98%) of children and adolescents with MS have a relapsing-remitting course. Overall, pediatric MS has a milder course than adult MS but can lead to significant disability at an early age. Although pediatric patients may experience more frequent relapses, data also suggest that children seem to recover more quickly from episodes than adults.

In children and adolescents, MS most typically manifests with sensory disturbances and impaired coordination. The most commonly reported symptoms in pediatric MS are sensory, motor, and brainstem dysfunction, though cognitive and emotional disorders can emerge over time.

Younger children will often show multifocal symptoms but with the onset of adolescence may begin to present with only a single focal symptom, as is often the case with adult patients.

Diagnosis of pediatric MS goes hand-in-hand with a diagnosis of clinically isolated syndrome (CIS) or sporadic acute disseminated encephalomyelitis (ADEM). CIS is diagnosed when symptoms last for over 24 hours with possible inflammatory demyelination but without encephalopathy. To confirm an MS diagnosis, two or more clinical episodes must occur at least 30 days apart. MRI can both confirm diagnosis and offer great value in monitoring disease progression in the brain and spinal cord. Of note, differentiating the first episode of juvenile MS from ADEM is a significant clinical challenge.

When it comes to treating relapses, the approach in children is similar to that of adults. Therapy may consist of an intravenous pulse of methylprednisolone (20-30 mg/kg/day for 3-5 days). In 2018, the FDA approved the use of the oral MS therapy Gilenya (fingolimod) for the treatment of patients 10 years of age or older with relapsing forms of MS. Providers can also adapt treatments approved for adults for pediatric patients. 

Krupa Pandey, MD, Director, Multiple Sclerosis Center, Department of Neurology & Neuroscience Institute, Hackensack University Medical Center; Neurologist, Department of Neurology, Hackensack Meridian Health, Hackensack, NJ

Krupa Pandey, MD, has serve(d) as a speaker or a member of a speakers bureau for: Bristol-Myers Squibb; Biogen; Alexion; Genentech; Sanofi-Genzyme

The patient is probably presenting with relapsing-remitting multiple sclerosis (RRMS). MS is characterized by symptomatic episodes that are heralded by symptoms of central nervous system involvement. These attacks last longer than 24 hours and may occur months or years apart and affect different anatomic locations. Consistent with other autoimmune conditions, MS is more common in women. Patients are usually diagnosed between the ages of 20 and 49 years. The condition presents differently from patient to patient; some experience cognitive changes or visual symptoms, while others may have numbness, ataxia, clumsiness, hemiparesis, paraparesis, depression, or seizures. Symptoms can also include fatigue, impaired mobility, mood diagnosed changes, elimination dysfunction, and pain.

Of the four disease courses identified in MS, the most common is RRMS, characterized by a cycle of relapse and remission. In the initial stages, RRMS is characterized largely by an inflammatory pathology which, over time, becomes largely neurodegenerative. Most cases of RRMS evolve to secondary progressive MS after about 15 years. Early in the spectrum of demyelinating disease is clinically isolated syndrome (CIS), defined by a single episode of neurologic symptoms and MRI showing more than two classic lesions seen in MS. CIS patients subsequently will present with a second episode or relapse, at which point the diagnosis of RRMS is usually confirmed.

MS is diagnosed on the basis of clinical findings, exclusion of mimickers, and supporting evidence from the workup, namely MRI of the brain and spinal cord as well as cerebrospinal fluid examination. From a clinical perspective, presentation must align with the constellation of neurologic deficits seen in MS. Typically, the duration of deficit is days to weeks, as seen in the present case. While MRI alone cannot be used to diagnose MS, imaging may confirm diagnosis and offer value in monitoring disease progression in the brain and spinal cord. New lesions on MRI usually occur with relapses in RRMS. 

Treatment of MS encompasses immunomodulatory therapy to address the underlying immune disorder together with therapies to relieve symptoms. In general, disease-modifying therapy (DMT) should be considered for patients who have experienced a single demyelinating event and exhibit two or more brain lesions on MRI testing. This recommendation holds true even for patients with CIS or those who have experienced their first clinical event and have MRI features consistent with MS, so long as all other conditions in the differential are ruled out. Pivotal trials support the early initiation of DMT with CIS to delay disability.

Krupa Pandey, MD, Director, Multiple Sclerosis Center, Department of Neurology & Neuroscience Institute, Hackensack University Medical Center; Neurologist, Department of Neurology, Hackensack Meridian Health, Hackensack, NJ

Krupa Pandey, MD, has serve(d) as a speaker or a member of a speakers bureau for: Bristol-Myers Squibb; Biogen; Alexion; Genentech; Sanofi-Genzyme

The patient is probably presenting with relapsing-remitting multiple sclerosis (RRMS). MS is characterized by symptomatic episodes that are heralded by symptoms of central nervous system involvement. These attacks last longer than 24 hours and may occur months or years apart and affect different anatomic locations. Consistent with other autoimmune conditions, MS is more common in women. Patients are usually diagnosed between the ages of 20 and 49 years. The condition presents differently from patient to patient; some experience cognitive changes or visual symptoms, while others may have numbness, ataxia, clumsiness, hemiparesis, paraparesis, depression, or seizures. Symptoms can also include fatigue, impaired mobility, mood diagnosed changes, elimination dysfunction, and pain.

Of the four disease courses identified in MS, the most common is RRMS, characterized by a cycle of relapse and remission. In the initial stages, RRMS is characterized largely by an inflammatory pathology which, over time, becomes largely neurodegenerative. Most cases of RRMS evolve to secondary progressive MS after about 15 years. Early in the spectrum of demyelinating disease is clinically isolated syndrome (CIS), defined by a single episode of neurologic symptoms and MRI showing more than two classic lesions seen in MS. CIS patients subsequently will present with a second episode or relapse, at which point the diagnosis of RRMS is usually confirmed.

MS is diagnosed on the basis of clinical findings, exclusion of mimickers, and supporting evidence from the workup, namely MRI of the brain and spinal cord as well as cerebrospinal fluid examination. From a clinical perspective, presentation must align with the constellation of neurologic deficits seen in MS. Typically, the duration of deficit is days to weeks, as seen in the present case. While MRI alone cannot be used to diagnose MS, imaging may confirm diagnosis and offer value in monitoring disease progression in the brain and spinal cord. New lesions on MRI usually occur with relapses in RRMS. 

Treatment of MS encompasses immunomodulatory therapy to address the underlying immune disorder together with therapies to relieve symptoms. In general, disease-modifying therapy (DMT) should be considered for patients who have experienced a single demyelinating event and exhibit two or more brain lesions on MRI testing. This recommendation holds true even for patients with CIS or those who have experienced their first clinical event and have MRI features consistent with MS, so long as all other conditions in the differential are ruled out. Pivotal trials support the early initiation of DMT with CIS to delay disability.

Krupa Pandey, MD, Director, Multiple Sclerosis Center, Department of Neurology & Neuroscience Institute, Hackensack University Medical Center; Neurologist, Department of Neurology, Hackensack Meridian Health, Hackensack, NJ

Krupa Pandey, MD, has serve(d) as a speaker or a member of a speakers bureau for: Bristol-Myers Squibb; Biogen; Alexion; Genentech; Sanofi-Genzyme

The patient is probably presenting with relapsing-remitting multiple sclerosis (RRMS). MS is characterized by symptomatic episodes that are heralded by symptoms of central nervous system involvement. These attacks last longer than 24 hours and may occur months or years apart and affect different anatomic locations. Consistent with other autoimmune conditions, MS is more common in women. Patients are usually diagnosed between the ages of 20 and 49 years. The condition presents differently from patient to patient; some experience cognitive changes or visual symptoms, while others may have numbness, ataxia, clumsiness, hemiparesis, paraparesis, depression, or seizures. Symptoms can also include fatigue, impaired mobility, mood diagnosed changes, elimination dysfunction, and pain.

Of the four disease courses identified in MS, the most common is RRMS, characterized by a cycle of relapse and remission. In the initial stages, RRMS is characterized largely by an inflammatory pathology which, over time, becomes largely neurodegenerative. Most cases of RRMS evolve to secondary progressive MS after about 15 years. Early in the spectrum of demyelinating disease is clinically isolated syndrome (CIS), defined by a single episode of neurologic symptoms and MRI showing more than two classic lesions seen in MS. CIS patients subsequently will present with a second episode or relapse, at which point the diagnosis of RRMS is usually confirmed.

MS is diagnosed on the basis of clinical findings, exclusion of mimickers, and supporting evidence from the workup, namely MRI of the brain and spinal cord as well as cerebrospinal fluid examination. From a clinical perspective, presentation must align with the constellation of neurologic deficits seen in MS. Typically, the duration of deficit is days to weeks, as seen in the present case. While MRI alone cannot be used to diagnose MS, imaging may confirm diagnosis and offer value in monitoring disease progression in the brain and spinal cord. New lesions on MRI usually occur with relapses in RRMS. 

Treatment of MS encompasses immunomodulatory therapy to address the underlying immune disorder together with therapies to relieve symptoms. In general, disease-modifying therapy (DMT) should be considered for patients who have experienced a single demyelinating event and exhibit two or more brain lesions on MRI testing. This recommendation holds true even for patients with CIS or those who have experienced their first clinical event and have MRI features consistent with MS, so long as all other conditions in the differential are ruled out. Pivotal trials support the early initiation of DMT with CIS to delay disability.

Krupa Pandey, MD, Director, Multiple Sclerosis Center, Department of Neurology & Neuroscience Institute, Hackensack University Medical Center; Neurologist, Department of Neurology, Hackensack Meridian Health, Hackensack, NJ

Krupa Pandey, MD, has serve(d) as a speaker or a member of a speakers bureau for: Bristol-Myers Squibb; Biogen; Alexion; Genentech; Sanofi-Genzyme

The patient is probably presenting with a moderate asthma exacerbation. To confirm the diagnosis, spirometry assessments should be performed to establish the presence of baseline airway obstruction and determine its severity. Measurements should be obtained before and after inhalation of a short-acting bronchodilator. In addition, chest radiography can help to exclude other diagnoses, and pulse oximetry can exclude hypoxemia.

Asthma is a heterogeneous inflammatory disease and the most common chronic condition among children. Histologically, it is marked by vascular congestion, increased vascular permeability, increased tissue volume, and the presence of an exudate. Because the asthmatic lung undergoes a cycle of injury, repair, and regeneration, inflammation creates histologic changes and functional abnormalities in the airway mucosal epithelium. It is hypothesized that these changes play a major role in the pathophysiology of asthma. 

Eosinophilic infiltration is a hallmark of this inflammatory activity. Histologic evaluations of the large airways may also reveal narrowing of lumina, bronchial and bronchiolar epithelial denudation, and mucus plugs. Other relevant findings can include epithelial desquamation and hyperplasia, goblet cell metaplasia, subbasement membrane thickening, smooth muscle hypertrophy or hyperplasia, and submucosal gland hypertrophy. In patients with severe asthma, the basement membrane may be significantly thickened. In terms of the small airways, pathologic study from the lungs of living patients is rarely undertaken, and therefore the histopathologic findings of asthma at the level of the distal airways and alveolated lung parenchyma remains largely unknown.

Asthma is treated using a stepwise approach. As directed for pediatric patients younger than 5 years, the patient in this case may be provided with an as-needed inhaled short-acting beta2-agonist (SABA) and should be followed up every 2-6 weeks while gaining control of her symptoms.

Nathan L. Boyer, MD, Assistant Professor, Department of Medicine, Uniformed Services University, Bethesda, Maryland; Chief of Critical Care, Landstuhl Regional Medical Center, Landstuhl, Germany.

Nathan L. Boyer, MD, has disclosed no relevant financial relationships.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.
 

The patient is probably presenting with a moderate asthma exacerbation. To confirm the diagnosis, spirometry assessments should be performed to establish the presence of baseline airway obstruction and determine its severity. Measurements should be obtained before and after inhalation of a short-acting bronchodilator. In addition, chest radiography can help to exclude other diagnoses, and pulse oximetry can exclude hypoxemia.

Asthma is a heterogeneous inflammatory disease and the most common chronic condition among children. Histologically, it is marked by vascular congestion, increased vascular permeability, increased tissue volume, and the presence of an exudate. Because the asthmatic lung undergoes a cycle of injury, repair, and regeneration, inflammation creates histologic changes and functional abnormalities in the airway mucosal epithelium. It is hypothesized that these changes play a major role in the pathophysiology of asthma. 

Eosinophilic infiltration is a hallmark of this inflammatory activity. Histologic evaluations of the large airways may also reveal narrowing of lumina, bronchial and bronchiolar epithelial denudation, and mucus plugs. Other relevant findings can include epithelial desquamation and hyperplasia, goblet cell metaplasia, subbasement membrane thickening, smooth muscle hypertrophy or hyperplasia, and submucosal gland hypertrophy. In patients with severe asthma, the basement membrane may be significantly thickened. In terms of the small airways, pathologic study from the lungs of living patients is rarely undertaken, and therefore the histopathologic findings of asthma at the level of the distal airways and alveolated lung parenchyma remains largely unknown.

Asthma is treated using a stepwise approach. As directed for pediatric patients younger than 5 years, the patient in this case may be provided with an as-needed inhaled short-acting beta2-agonist (SABA) and should be followed up every 2-6 weeks while gaining control of her symptoms.

Nathan L. Boyer, MD, Assistant Professor, Department of Medicine, Uniformed Services University, Bethesda, Maryland; Chief of Critical Care, Landstuhl Regional Medical Center, Landstuhl, Germany.

Nathan L. Boyer, MD, has disclosed no relevant financial relationships.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.
 

The patient is probably presenting with a moderate asthma exacerbation. To confirm the diagnosis, spirometry assessments should be performed to establish the presence of baseline airway obstruction and determine its severity. Measurements should be obtained before and after inhalation of a short-acting bronchodilator. In addition, chest radiography can help to exclude other diagnoses, and pulse oximetry can exclude hypoxemia.

Asthma is a heterogeneous inflammatory disease and the most common chronic condition among children. Histologically, it is marked by vascular congestion, increased vascular permeability, increased tissue volume, and the presence of an exudate. Because the asthmatic lung undergoes a cycle of injury, repair, and regeneration, inflammation creates histologic changes and functional abnormalities in the airway mucosal epithelium. It is hypothesized that these changes play a major role in the pathophysiology of asthma. 

Eosinophilic infiltration is a hallmark of this inflammatory activity. Histologic evaluations of the large airways may also reveal narrowing of lumina, bronchial and bronchiolar epithelial denudation, and mucus plugs. Other relevant findings can include epithelial desquamation and hyperplasia, goblet cell metaplasia, subbasement membrane thickening, smooth muscle hypertrophy or hyperplasia, and submucosal gland hypertrophy. In patients with severe asthma, the basement membrane may be significantly thickened. In terms of the small airways, pathologic study from the lungs of living patients is rarely undertaken, and therefore the histopathologic findings of asthma at the level of the distal airways and alveolated lung parenchyma remains largely unknown.

Asthma is treated using a stepwise approach. As directed for pediatric patients younger than 5 years, the patient in this case may be provided with an as-needed inhaled short-acting beta2-agonist (SABA) and should be followed up every 2-6 weeks while gaining control of her symptoms.

Nathan L. Boyer, MD, Assistant Professor, Department of Medicine, Uniformed Services University, Bethesda, Maryland; Chief of Critical Care, Landstuhl Regional Medical Center, Landstuhl, Germany.

Nathan L. Boyer, MD, has disclosed no relevant financial relationships.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.
 

Superinfected eczema is an inflammation of the skin accompanied by itchy, weeping, oozing lesions. Secondary infection of the open skin can occur as a result of scratching. In this case, the infection was a consequence of sensitivity to wearing shin pads. 

Although superinfected eczema is a complication of eczema, it can produce separate challenges. With damaged protective skin function and disturbance of quantity and quality of skin lipids, patients with eczema may have secondary bacterial infections. Staphylococcus aureus organisms are the most common etiologic agents; up to 90% of patients with eczema have staphylococcal colonization. Streptococcus is less commonly a cause. The progression from colonization to infection often is associated with a flare of eczema, and increased severity of the eczema is associated with more colonization. More erythema may be noted when the infection begins; then, the affected areas become encrusted or show a serous drainage. A clinical clue to superinfection of any kind is when patients stop responding to therapies that they are normally responsive to (eg, topical steroids). 

With the recent increase in methicillin-resistant S. aureus (MRSA), treatment of a secondary infection of eczema with these organisms can be tricky. Patients with eczema and secondary bacterial skin infections should be treated with topical steroids or other anti-inflammatory medications and moisturizers to repair the skin barrier. The level of skin colonization with S. aureus is decreased with use of these agents alone. Topical or systemic antibiotics appropriate for specific or community-based sensitivities may be needed in severe infections.

Because of the damaged protective skin function, cutaneous inoculation of herpes simplex virus (HSV) can occur. Eczema herpeticum, or HSV-associated Kaposi varicelliform eruption, describes eczema secondarily infected with HSV (type 1 or type 2). The eczema may become more erythematous; then, vesicles develop that are arranged in a grouped pattern. Accompanying symptoms include fever, malaise, and lymphadenopathy. The condition can be diagnosed by a Tzanck smear (seeking multinucleated giant cells), a fluorescent antibody smear, or culture of a vesicular lesion. Patients with eczema herpeticum should be treated with acyclovir. More severe involvement may require hospitalization and use of systemic antivirals. In addition, topical steroids and moisturizers should be continued to repair the skin barrier. 

Children with eczema are more likely than adults to acquire molluscum contagiosum infection, and the disease tends to be widespread. The lesions are generally smooth papules, sometimes with umbilicated skin. The lesions can spread by auto-inoculation to surrounding areas. Molluscum dermatitis accompanies 10% of molluscum lesions, and the dermatitis can be difficult to distinguish from eczema lesions. Untreated, molluscum lesions may resolve on their own; if necessary, the lesions can be treated with cantharidin, liquid nitrogen, or curettage. 

Molluscum dermatitis is treated with topical steroids. Early recognition of infections associated with a diagnosis of eczema is critical for timely initiation of appropriate treatment.
 

Brian S. Kim, MD, Associate Professor, Department of Medicine, Division of Dermatology, Washington University School of Medicine, St. Louis, Missouri

Brian S. Kim, MD, has disclosed no relevant financial relationships.

Superinfected eczema is an inflammation of the skin accompanied by itchy, weeping, oozing lesions. Secondary infection of the open skin can occur as a result of scratching. In this case, the infection was a consequence of sensitivity to wearing shin pads. 

Although superinfected eczema is a complication of eczema, it can produce separate challenges. With damaged protective skin function and disturbance of quantity and quality of skin lipids, patients with eczema may have secondary bacterial infections. Staphylococcus aureus organisms are the most common etiologic agents; up to 90% of patients with eczema have staphylococcal colonization. Streptococcus is less commonly a cause. The progression from colonization to infection often is associated with a flare of eczema, and increased severity of the eczema is associated with more colonization. More erythema may be noted when the infection begins; then, the affected areas become encrusted or show a serous drainage. A clinical clue to superinfection of any kind is when patients stop responding to therapies that they are normally responsive to (eg, topical steroids). 

With the recent increase in methicillin-resistant S. aureus (MRSA), treatment of a secondary infection of eczema with these organisms can be tricky. Patients with eczema and secondary bacterial skin infections should be treated with topical steroids or other anti-inflammatory medications and moisturizers to repair the skin barrier. The level of skin colonization with S. aureus is decreased with use of these agents alone. Topical or systemic antibiotics appropriate for specific or community-based sensitivities may be needed in severe infections.

Because of the damaged protective skin function, cutaneous inoculation of herpes simplex virus (HSV) can occur. Eczema herpeticum, or HSV-associated Kaposi varicelliform eruption, describes eczema secondarily infected with HSV (type 1 or type 2). The eczema may become more erythematous; then, vesicles develop that are arranged in a grouped pattern. Accompanying symptoms include fever, malaise, and lymphadenopathy. The condition can be diagnosed by a Tzanck smear (seeking multinucleated giant cells), a fluorescent antibody smear, or culture of a vesicular lesion. Patients with eczema herpeticum should be treated with acyclovir. More severe involvement may require hospitalization and use of systemic antivirals. In addition, topical steroids and moisturizers should be continued to repair the skin barrier. 

Children with eczema are more likely than adults to acquire molluscum contagiosum infection, and the disease tends to be widespread. The lesions are generally smooth papules, sometimes with umbilicated skin. The lesions can spread by auto-inoculation to surrounding areas. Molluscum dermatitis accompanies 10% of molluscum lesions, and the dermatitis can be difficult to distinguish from eczema lesions. Untreated, molluscum lesions may resolve on their own; if necessary, the lesions can be treated with cantharidin, liquid nitrogen, or curettage. 

Molluscum dermatitis is treated with topical steroids. Early recognition of infections associated with a diagnosis of eczema is critical for timely initiation of appropriate treatment.
 

Brian S. Kim, MD, Associate Professor, Department of Medicine, Division of Dermatology, Washington University School of Medicine, St. Louis, Missouri

Brian S. Kim, MD, has disclosed no relevant financial relationships.

Superinfected eczema is an inflammation of the skin accompanied by itchy, weeping, oozing lesions. Secondary infection of the open skin can occur as a result of scratching. In this case, the infection was a consequence of sensitivity to wearing shin pads. 

Although superinfected eczema is a complication of eczema, it can produce separate challenges. With damaged protective skin function and disturbance of quantity and quality of skin lipids, patients with eczema may have secondary bacterial infections. Staphylococcus aureus organisms are the most common etiologic agents; up to 90% of patients with eczema have staphylococcal colonization. Streptococcus is less commonly a cause. The progression from colonization to infection often is associated with a flare of eczema, and increased severity of the eczema is associated with more colonization. More erythema may be noted when the infection begins; then, the affected areas become encrusted or show a serous drainage. A clinical clue to superinfection of any kind is when patients stop responding to therapies that they are normally responsive to (eg, topical steroids). 

With the recent increase in methicillin-resistant S. aureus (MRSA), treatment of a secondary infection of eczema with these organisms can be tricky. Patients with eczema and secondary bacterial skin infections should be treated with topical steroids or other anti-inflammatory medications and moisturizers to repair the skin barrier. The level of skin colonization with S. aureus is decreased with use of these agents alone. Topical or systemic antibiotics appropriate for specific or community-based sensitivities may be needed in severe infections.

Because of the damaged protective skin function, cutaneous inoculation of herpes simplex virus (HSV) can occur. Eczema herpeticum, or HSV-associated Kaposi varicelliform eruption, describes eczema secondarily infected with HSV (type 1 or type 2). The eczema may become more erythematous; then, vesicles develop that are arranged in a grouped pattern. Accompanying symptoms include fever, malaise, and lymphadenopathy. The condition can be diagnosed by a Tzanck smear (seeking multinucleated giant cells), a fluorescent antibody smear, or culture of a vesicular lesion. Patients with eczema herpeticum should be treated with acyclovir. More severe involvement may require hospitalization and use of systemic antivirals. In addition, topical steroids and moisturizers should be continued to repair the skin barrier. 

Children with eczema are more likely than adults to acquire molluscum contagiosum infection, and the disease tends to be widespread. The lesions are generally smooth papules, sometimes with umbilicated skin. The lesions can spread by auto-inoculation to surrounding areas. Molluscum dermatitis accompanies 10% of molluscum lesions, and the dermatitis can be difficult to distinguish from eczema lesions. Untreated, molluscum lesions may resolve on their own; if necessary, the lesions can be treated with cantharidin, liquid nitrogen, or curettage. 

Molluscum dermatitis is treated with topical steroids. Early recognition of infections associated with a diagnosis of eczema is critical for timely initiation of appropriate treatment.
 

Brian S. Kim, MD, Associate Professor, Department of Medicine, Division of Dermatology, Washington University School of Medicine, St. Louis, Missouri

Brian S. Kim, MD, has disclosed no relevant financial relationships.

Transrectal ultrasonography (TRUS)–guided needle biopsy of the prostate confirms a diagnosis of high-grade prostate cancer, and the digital rectal exam and CT scan are concerning for extracapsular invasion. Genetic and molecular biomarker testing is recommended.

According to GLOBOCAN 2020 data, prostate cancer is the second most common type of cancer in men (second only to lung cancer) and the fifth leading cause of death globally. Compared with other races, the incidence of prostate cancer in the United States is highest in Black men, and mortality rates are more than double than those reported in White men. In its early stages, prostate cancer is often asymptomatic and has an indolent course. Locally advanced prostate cancer is a clinical scenario in which the cancer has extended beyond the prostatic capsule. It involves invasion of the pericapsular tissue, bladder neck, or seminal vesicles, without lymph node involvement or distant metastases. Biological recurrence, metastatic progression, and poor survival are associated with locally advanced prostate cancer.

In the presence of advanced disease, troublesome lower urinary tract symptoms — particularly abnormal growth of prostate cancer–induced bladder outlet obstruction — are often reported. Such symptoms have a significant impact on patients' quality of life. Other symptoms of locally advanced disease may include hematuria, pain, urinary retention, urinary incontinence, hematospermia, painful ejaculation, anejaculation, constipation, and hematochezia.

Guideline-based approaches to the management of prostate cancer begin with appropriate risk stratification based on biopsy, physical examination, and imaging evaluation. In patients with advanced prostate cancer, treatment decisions should incorporate a multidisciplinary approach and include consideration of life expectancy, comorbidities, patient preferences, and tumor characteristics. Establishing whether the patient has widely advanced disease vs locally advanced disease (clinical stage T3) is helpful for ascertaining which treatment options are available. Pain control and other supportive therapies should be optimized in cases involving advanced prostate cancer. 

Androgen deprivation therapy (ADT), combined with luteinizing hormone–releasing hormone (LHRH) agonists or surgical castration, is considered first-line treatment for advanced metastatic prostate cancer. Abundant data show that ADT in advanced symptomatic metastatic prostate cancer, either in the form of surgical castration or LHRH analogues, is beneficial chiefly for palliation of symptoms. However, the combination of ADT with radical prostatectomy or radiation therapy has been shown to improve overall and cancer-specific survival in selected patients with nonmetastatic but locally advanced prostate cancer. Recently, a prospective study showed a significant improvement in urodynamic variables and International Prostate Symptom Score (IPSS) questionnaire results, including IPSS-related quality of life, in patients with advanced cancer who received ADT, although lower urinary tract symptoms persist in some patients.

For patients with metastatic hormone-sensitive prostate cancer (mHSPC), continued treatment with ADT in combination with either androgen pathway–directed therapy (abiraterone acetate plus prednisone, apalutamide, enzalutamide) or chemotherapy (docetaxel) is generally recommended. A recent meta-analysis found that the next-generation androgen receptor inhibitors abiraterone, apalutamide, and enzalutamide appear to be significantly more effective than ADT and more effective than docetaxel for mHSPC; apalutamide was the best tolerated. For selected patients with mHSPC with low-volume metastatic disease, primary radiation therapy to the prostate in combination with ADT may be offered. First-generation antiandrogens (bicalutamide, flutamide, nilutamide) in combination with LHRH agonists are not recommended for patients with mHSPC, unless needed to block testosterone flare. In addition, oral androgen pathway–directed therapy (eg, abiraterone acetate plus prednisone, apalutamide, bicalutamide, darolutamide, enzalutamide, flutamide, nilutamide) without ADT is not recommended for patients with mHSPC. 

In patients with nonmetastatic castration-resistant prostate cancer (nmCRPC), darolutamide, apalutamide, and enzalutamide with continued ADT have been shown to postpone the onset of metastases and death. Unless within the context of a clinical trial, systemic chemotherapy or immunotherapy should not be offered to patients with nmCRPC. 

For patients with newly diagnosed metastatic castration-resistant prostate cancer (mCRPC), continued ADT with abiraterone acetate plus prednisone, docetaxel, or enzalutamide is recommended. For patients with mCRPC who are asymptomatic or minimally symptomatic, sipuleucel-T may be offered. At present, radium-223 is the only available therapy for mCRPC that specifically targets bone metastases, delays development of skeletal-related events, and improves survival. On the basis of results of the ALSYMPCA study, radium-223 in combination with systemic therapies is now considered an effective, efficient, and well-tolerated therapy for patients with castration-resistant prostate cancer with bone lesions. The effects of local radiation therapy for men with metastatic prostate cancer and the optimal combination of systemic therapies in the metastatic setting are still under investigation.

Complete recommendations on sequencing agents and selecting therapies for patients with advanced prostate cancer can be found in guidelines from the American Urological Association, National Comprehensive Cancer Network, and the European Association of Urology.

Kyle A. Richards, MD, Assistant Professor, Department of Urology, University of Wisconsin-Madison; Chief of Urology, William S. Middleton Memorial VA Hospital, Madison, Wisconsin

Kyle A. Richards, MD, has disclosed no relevant financial relationships

Transrectal ultrasonography (TRUS)–guided needle biopsy of the prostate confirms a diagnosis of high-grade prostate cancer, and the digital rectal exam and CT scan are concerning for extracapsular invasion. Genetic and molecular biomarker testing is recommended.

According to GLOBOCAN 2020 data, prostate cancer is the second most common type of cancer in men (second only to lung cancer) and the fifth leading cause of death globally. Compared with other races, the incidence of prostate cancer in the United States is highest in Black men, and mortality rates are more than double than those reported in White men. In its early stages, prostate cancer is often asymptomatic and has an indolent course. Locally advanced prostate cancer is a clinical scenario in which the cancer has extended beyond the prostatic capsule. It involves invasion of the pericapsular tissue, bladder neck, or seminal vesicles, without lymph node involvement or distant metastases. Biological recurrence, metastatic progression, and poor survival are associated with locally advanced prostate cancer.

In the presence of advanced disease, troublesome lower urinary tract symptoms — particularly abnormal growth of prostate cancer–induced bladder outlet obstruction — are often reported. Such symptoms have a significant impact on patients' quality of life. Other symptoms of locally advanced disease may include hematuria, pain, urinary retention, urinary incontinence, hematospermia, painful ejaculation, anejaculation, constipation, and hematochezia.

Guideline-based approaches to the management of prostate cancer begin with appropriate risk stratification based on biopsy, physical examination, and imaging evaluation. In patients with advanced prostate cancer, treatment decisions should incorporate a multidisciplinary approach and include consideration of life expectancy, comorbidities, patient preferences, and tumor characteristics. Establishing whether the patient has widely advanced disease vs locally advanced disease (clinical stage T3) is helpful for ascertaining which treatment options are available. Pain control and other supportive therapies should be optimized in cases involving advanced prostate cancer. 

Androgen deprivation therapy (ADT), combined with luteinizing hormone–releasing hormone (LHRH) agonists or surgical castration, is considered first-line treatment for advanced metastatic prostate cancer. Abundant data show that ADT in advanced symptomatic metastatic prostate cancer, either in the form of surgical castration or LHRH analogues, is beneficial chiefly for palliation of symptoms. However, the combination of ADT with radical prostatectomy or radiation therapy has been shown to improve overall and cancer-specific survival in selected patients with nonmetastatic but locally advanced prostate cancer. Recently, a prospective study showed a significant improvement in urodynamic variables and International Prostate Symptom Score (IPSS) questionnaire results, including IPSS-related quality of life, in patients with advanced cancer who received ADT, although lower urinary tract symptoms persist in some patients.

For patients with metastatic hormone-sensitive prostate cancer (mHSPC), continued treatment with ADT in combination with either androgen pathway–directed therapy (abiraterone acetate plus prednisone, apalutamide, enzalutamide) or chemotherapy (docetaxel) is generally recommended. A recent meta-analysis found that the next-generation androgen receptor inhibitors abiraterone, apalutamide, and enzalutamide appear to be significantly more effective than ADT and more effective than docetaxel for mHSPC; apalutamide was the best tolerated. For selected patients with mHSPC with low-volume metastatic disease, primary radiation therapy to the prostate in combination with ADT may be offered. First-generation antiandrogens (bicalutamide, flutamide, nilutamide) in combination with LHRH agonists are not recommended for patients with mHSPC, unless needed to block testosterone flare. In addition, oral androgen pathway–directed therapy (eg, abiraterone acetate plus prednisone, apalutamide, bicalutamide, darolutamide, enzalutamide, flutamide, nilutamide) without ADT is not recommended for patients with mHSPC. 

In patients with nonmetastatic castration-resistant prostate cancer (nmCRPC), darolutamide, apalutamide, and enzalutamide with continued ADT have been shown to postpone the onset of metastases and death. Unless within the context of a clinical trial, systemic chemotherapy or immunotherapy should not be offered to patients with nmCRPC. 

For patients with newly diagnosed metastatic castration-resistant prostate cancer (mCRPC), continued ADT with abiraterone acetate plus prednisone, docetaxel, or enzalutamide is recommended. For patients with mCRPC who are asymptomatic or minimally symptomatic, sipuleucel-T may be offered. At present, radium-223 is the only available therapy for mCRPC that specifically targets bone metastases, delays development of skeletal-related events, and improves survival. On the basis of results of the ALSYMPCA study, radium-223 in combination with systemic therapies is now considered an effective, efficient, and well-tolerated therapy for patients with castration-resistant prostate cancer with bone lesions. The effects of local radiation therapy for men with metastatic prostate cancer and the optimal combination of systemic therapies in the metastatic setting are still under investigation.

Complete recommendations on sequencing agents and selecting therapies for patients with advanced prostate cancer can be found in guidelines from the American Urological Association, National Comprehensive Cancer Network, and the European Association of Urology.

Kyle A. Richards, MD, Assistant Professor, Department of Urology, University of Wisconsin-Madison; Chief of Urology, William S. Middleton Memorial VA Hospital, Madison, Wisconsin

Kyle A. Richards, MD, has disclosed no relevant financial relationships

Transrectal ultrasonography (TRUS)–guided needle biopsy of the prostate confirms a diagnosis of high-grade prostate cancer, and the digital rectal exam and CT scan are concerning for extracapsular invasion. Genetic and molecular biomarker testing is recommended.

According to GLOBOCAN 2020 data, prostate cancer is the second most common type of cancer in men (second only to lung cancer) and the fifth leading cause of death globally. Compared with other races, the incidence of prostate cancer in the United States is highest in Black men, and mortality rates are more than double than those reported in White men. In its early stages, prostate cancer is often asymptomatic and has an indolent course. Locally advanced prostate cancer is a clinical scenario in which the cancer has extended beyond the prostatic capsule. It involves invasion of the pericapsular tissue, bladder neck, or seminal vesicles, without lymph node involvement or distant metastases. Biological recurrence, metastatic progression, and poor survival are associated with locally advanced prostate cancer.

In the presence of advanced disease, troublesome lower urinary tract symptoms — particularly abnormal growth of prostate cancer–induced bladder outlet obstruction — are often reported. Such symptoms have a significant impact on patients' quality of life. Other symptoms of locally advanced disease may include hematuria, pain, urinary retention, urinary incontinence, hematospermia, painful ejaculation, anejaculation, constipation, and hematochezia.

Guideline-based approaches to the management of prostate cancer begin with appropriate risk stratification based on biopsy, physical examination, and imaging evaluation. In patients with advanced prostate cancer, treatment decisions should incorporate a multidisciplinary approach and include consideration of life expectancy, comorbidities, patient preferences, and tumor characteristics. Establishing whether the patient has widely advanced disease vs locally advanced disease (clinical stage T3) is helpful for ascertaining which treatment options are available. Pain control and other supportive therapies should be optimized in cases involving advanced prostate cancer. 

Androgen deprivation therapy (ADT), combined with luteinizing hormone–releasing hormone (LHRH) agonists or surgical castration, is considered first-line treatment for advanced metastatic prostate cancer. Abundant data show that ADT in advanced symptomatic metastatic prostate cancer, either in the form of surgical castration or LHRH analogues, is beneficial chiefly for palliation of symptoms. However, the combination of ADT with radical prostatectomy or radiation therapy has been shown to improve overall and cancer-specific survival in selected patients with nonmetastatic but locally advanced prostate cancer. Recently, a prospective study showed a significant improvement in urodynamic variables and International Prostate Symptom Score (IPSS) questionnaire results, including IPSS-related quality of life, in patients with advanced cancer who received ADT, although lower urinary tract symptoms persist in some patients.

For patients with metastatic hormone-sensitive prostate cancer (mHSPC), continued treatment with ADT in combination with either androgen pathway–directed therapy (abiraterone acetate plus prednisone, apalutamide, enzalutamide) or chemotherapy (docetaxel) is generally recommended. A recent meta-analysis found that the next-generation androgen receptor inhibitors abiraterone, apalutamide, and enzalutamide appear to be significantly more effective than ADT and more effective than docetaxel for mHSPC; apalutamide was the best tolerated. For selected patients with mHSPC with low-volume metastatic disease, primary radiation therapy to the prostate in combination with ADT may be offered. First-generation antiandrogens (bicalutamide, flutamide, nilutamide) in combination with LHRH agonists are not recommended for patients with mHSPC, unless needed to block testosterone flare. In addition, oral androgen pathway–directed therapy (eg, abiraterone acetate plus prednisone, apalutamide, bicalutamide, darolutamide, enzalutamide, flutamide, nilutamide) without ADT is not recommended for patients with mHSPC. 

In patients with nonmetastatic castration-resistant prostate cancer (nmCRPC), darolutamide, apalutamide, and enzalutamide with continued ADT have been shown to postpone the onset of metastases and death. Unless within the context of a clinical trial, systemic chemotherapy or immunotherapy should not be offered to patients with nmCRPC. 

For patients with newly diagnosed metastatic castration-resistant prostate cancer (mCRPC), continued ADT with abiraterone acetate plus prednisone, docetaxel, or enzalutamide is recommended. For patients with mCRPC who are asymptomatic or minimally symptomatic, sipuleucel-T may be offered. At present, radium-223 is the only available therapy for mCRPC that specifically targets bone metastases, delays development of skeletal-related events, and improves survival. On the basis of results of the ALSYMPCA study, radium-223 in combination with systemic therapies is now considered an effective, efficient, and well-tolerated therapy for patients with castration-resistant prostate cancer with bone lesions. The effects of local radiation therapy for men with metastatic prostate cancer and the optimal combination of systemic therapies in the metastatic setting are still under investigation.

Complete recommendations on sequencing agents and selecting therapies for patients with advanced prostate cancer can be found in guidelines from the American Urological Association, National Comprehensive Cancer Network, and the European Association of Urology.

Kyle A. Richards, MD, Assistant Professor, Department of Urology, University of Wisconsin-Madison; Chief of Urology, William S. Middleton Memorial VA Hospital, Madison, Wisconsin

Kyle A. Richards, MD, has disclosed no relevant financial relationships