E. Eugene Bain Iii, MD

The Diagnosis: Dermal Cylindroma

Microsopic evaluation of a tangential biopsy revealed findings of a dermal process consisting of well-circumscribed islands of pale and darker blue cells with little cytoplasm outlined by a hyaline basement membrane (Figure). These cellular islands were arranged in a jigsawlike configuration. These findings were thought to be consistent with a diagnosis of cylindroma.

Well-circumscribed dermal islands of both pale and darker blue cells outlined by a hyaline basement membrane. These cellular islands were arranged in a jigsawlike configuration (A and B)(both H&E, original magnifications ×20 and ×200).

Cylindromas are benign appendageal neoplasms with a somewhat controversial histogenesis. Munger and colleagues¹ investigated the pattern of acid mucopolysaccharide secretion by these tumors in association with prosecretory vacuoles in proximity to the Golgi apparatus, which led to their impression that cylindromas most resemble eccrine rather than apocrine sweat glands. Other researchers, however, have concluded that cylindromas are of apocrine derivation.²

Clinically, cylindromas appear most often in 2 settings: isolated or as a manifestation of one of several inherited familial syndromes. One such syndrome is familial cylindromatosis, a rare autosomal-dominant disorder in which affected individuals develop multiple cylindromas, usually on the head and neck. The merging of multiple lesions gives rise to the often-employed term turban tumor.³ This syndrome has been linked to mutations in the cylindromatosis gene, CYLD.⁴ Brooke-Spiegler syndrome also has been associated with the development of multiple cylindromas. Similar to familial cylindromatosis, it is inherited in an autosomal-dominant fashion. Brooke-Spiegler syndrome is typified by the appearance of multiple cylindromas, trichoepitheliomas, and less commonly spiradenomas. Mutations in the CYLD gene also have been linked to Brooke-Spiegler syndrome in some cases.⁵

Although considered a benign entity, in rare cases cylindromas have shown evidence of malignant transformation to cylindrocarcinoma. This more aggressive tumor may occur in the setting of isolated cylindromas or more commonly in individuals with numerous lesions, as with both familial cylindromatosis and Brooke-Spiegler syndrome. These lesions may appear to grow rapidly, ulcerate, or bleed, traits that are not associated with their benign counterparts.

Diagnosis of cylindromas rests on histopathologic confirmation, which demonstrates well-defined dermal islands of epithelial cells comprised of dark- and pale-staining nuclei. These tumor islands are surrounded by a hyaline basement membrane and often take on the appearance of a jigsaw puzzle. Cylindrocarcinomas exhibit greater cellular pleomorphism and higher mitotic rates.

Dermal cylindromas require no further treatment but can be electively excised, while treatment of cylindrocarcinoma with excision is curative.⁶ Definitive excision was offered to our patient, but she declined treatment.

The Diagnosis: Dermal Cylindroma

Microsopic evaluation of a tangential biopsy revealed findings of a dermal process consisting of well-circumscribed islands of pale and darker blue cells with little cytoplasm outlined by a hyaline basement membrane (Figure). These cellular islands were arranged in a jigsawlike configuration. These findings were thought to be consistent with a diagnosis of cylindroma.

Well-circumscribed dermal islands of both pale and darker blue cells outlined by a hyaline basement membrane. These cellular islands were arranged in a jigsawlike configuration (A and B)(both H&E, original magnifications ×20 and ×200).

Cylindromas are benign appendageal neoplasms with a somewhat controversial histogenesis. Munger and colleagues¹ investigated the pattern of acid mucopolysaccharide secretion by these tumors in association with prosecretory vacuoles in proximity to the Golgi apparatus, which led to their impression that cylindromas most resemble eccrine rather than apocrine sweat glands. Other researchers, however, have concluded that cylindromas are of apocrine derivation.²

Clinically, cylindromas appear most often in 2 settings: isolated or as a manifestation of one of several inherited familial syndromes. One such syndrome is familial cylindromatosis, a rare autosomal-dominant disorder in which affected individuals develop multiple cylindromas, usually on the head and neck. The merging of multiple lesions gives rise to the often-employed term turban tumor.³ This syndrome has been linked to mutations in the cylindromatosis gene, CYLD.⁴ Brooke-Spiegler syndrome also has been associated with the development of multiple cylindromas. Similar to familial cylindromatosis, it is inherited in an autosomal-dominant fashion. Brooke-Spiegler syndrome is typified by the appearance of multiple cylindromas, trichoepitheliomas, and less commonly spiradenomas. Mutations in the CYLD gene also have been linked to Brooke-Spiegler syndrome in some cases.⁵

Although considered a benign entity, in rare cases cylindromas have shown evidence of malignant transformation to cylindrocarcinoma. This more aggressive tumor may occur in the setting of isolated cylindromas or more commonly in individuals with numerous lesions, as with both familial cylindromatosis and Brooke-Spiegler syndrome. These lesions may appear to grow rapidly, ulcerate, or bleed, traits that are not associated with their benign counterparts.

Diagnosis of cylindromas rests on histopathologic confirmation, which demonstrates well-defined dermal islands of epithelial cells comprised of dark- and pale-staining nuclei. These tumor islands are surrounded by a hyaline basement membrane and often take on the appearance of a jigsaw puzzle. Cylindrocarcinomas exhibit greater cellular pleomorphism and higher mitotic rates.

Dermal cylindromas require no further treatment but can be electively excised, while treatment of cylindrocarcinoma with excision is curative.⁶ Definitive excision was offered to our patient, but she declined treatment.

The Diagnosis: Dermal Cylindroma

Microsopic evaluation of a tangential biopsy revealed findings of a dermal process consisting of well-circumscribed islands of pale and darker blue cells with little cytoplasm outlined by a hyaline basement membrane (Figure). These cellular islands were arranged in a jigsawlike configuration. These findings were thought to be consistent with a diagnosis of cylindroma.

Well-circumscribed dermal islands of both pale and darker blue cells outlined by a hyaline basement membrane. These cellular islands were arranged in a jigsawlike configuration (A and B)(both H&E, original magnifications ×20 and ×200).

Cylindromas are benign appendageal neoplasms with a somewhat controversial histogenesis. Munger and colleagues¹ investigated the pattern of acid mucopolysaccharide secretion by these tumors in association with prosecretory vacuoles in proximity to the Golgi apparatus, which led to their impression that cylindromas most resemble eccrine rather than apocrine sweat glands. Other researchers, however, have concluded that cylindromas are of apocrine derivation.²

Clinically, cylindromas appear most often in 2 settings: isolated or as a manifestation of one of several inherited familial syndromes. One such syndrome is familial cylindromatosis, a rare autosomal-dominant disorder in which affected individuals develop multiple cylindromas, usually on the head and neck. The merging of multiple lesions gives rise to the often-employed term turban tumor.³ This syndrome has been linked to mutations in the cylindromatosis gene, CYLD.⁴ Brooke-Spiegler syndrome also has been associated with the development of multiple cylindromas. Similar to familial cylindromatosis, it is inherited in an autosomal-dominant fashion. Brooke-Spiegler syndrome is typified by the appearance of multiple cylindromas, trichoepitheliomas, and less commonly spiradenomas. Mutations in the CYLD gene also have been linked to Brooke-Spiegler syndrome in some cases.⁵

Although considered a benign entity, in rare cases cylindromas have shown evidence of malignant transformation to cylindrocarcinoma. This more aggressive tumor may occur in the setting of isolated cylindromas or more commonly in individuals with numerous lesions, as with both familial cylindromatosis and Brooke-Spiegler syndrome. These lesions may appear to grow rapidly, ulcerate, or bleed, traits that are not associated with their benign counterparts.

Diagnosis of cylindromas rests on histopathologic confirmation, which demonstrates well-defined dermal islands of epithelial cells comprised of dark- and pale-staining nuclei. These tumor islands are surrounded by a hyaline basement membrane and often take on the appearance of a jigsaw puzzle. Cylindrocarcinomas exhibit greater cellular pleomorphism and higher mitotic rates.

Dermal cylindromas require no further treatment but can be electively excised, while treatment of cylindrocarcinoma with excision is curative.⁶ Definitive excision was offered to our patient, but she declined treatment.

Most physicians do a satisfactory job in choosing when and how to do a skin biopsy, but there is always room for improvement. The 9 pointers we provide here are based on standard of care practices and literature when available, and also on our collective experiences as a pathologist/dermatologist (JM), dermatopathologist (DZ), primary care physician (BR), and dermatologist/Mohs surgeon (EB).

1. Choose your biopsy type wisely.

Using the appropriate type of biopsy can have the greatest effect on a proper diagnosis. The decision of which biopsy type to use is not always easy. The most common biopsy types are shave, punch, excisional, and curettage. Several reference articles detail each type of biopsy commonly used in primary care and how to perform them.^1,2 (For a series of how-to videos that illustrate how to perform some of these biopsies, visit The Journal of Family Practice Multimedia Library at http://www.jfponline.com/multimedia/video.html.)

Each type of biopsy has inherent advantages and disadvantages. In general, the shave biopsy is most commonly used for lesions that are solitary, elevated, and give the impression that a sufficient amount of tissue can be sampled using this technique. The punch biopsy is the biopsy of choice for most “rashes” (inflammatory skin disorders).² Excisional biopsy is used to remove melanocytic neoplasms or larger lesions. And curettage, while still used by some clinicians for melanocytic lesions because of its speed and simplicity, should almost never be used for diagnostic purposes. Each of these techniques is described in greater detail in the tips that follow.

2. When performing a shave biopsy, avoid obtaining a sample that's too superficial.

The advantage of the shave biopsy is that it is minimally invasive and quick to perform. If kept small while not compromising the amount of sample retrieved, the scars left by shave biopsies have the potential to blend well. The major disadvantage of the shave biopsy is that occasionally, if the shave is not deep enough, an insufficient amount of tissue is obtained, which can make it challenging to establish an accurate diagnosis.

An advantage 
of the punch biopsy is that patients are left with linear scars, rather than the round scars that are often associated with shave biopsy.Balancing the need to obtain adequate tissue while minimizing scarring takes skill and experience. Taking a biopsy that is inadequate is a common occurrence. At times, the physician’s clinical impression may be that a biopsy has obtained adequate tissue, but histologically only the superficial part of the skin surface has been sampled. This often is because of thickening of the superficial skin, whether as a manifestation of the anatomic site (eg, acral skin) or the disease process itself.

Unfortunately, this superficial skin often is nondiagnostic when unaccompanied by underlying epidermis and dermis. It is important to keep this in mind when obtaining a skin biopsy, especially when dealing with lesions that are very scaly or keratinized. An equivocal biopsy wastes time, energy, and money, and can negatively impact patient care.³ It can be difficult to balance practical aspects of the biopsy (ie, optimizing cosmetic outcomes, minimizing scarring and wound size) with the need to obtain sufficient tissue sampling (FIGURE 1).

3. Choose punch over shave biopsy for rashes.

In a punch biopsy, a disposable metal cylinder with a sharpened edge is used to “punch” out a piece of skin that can be examined under the microscope. Punch biopsy is the preferred technique for almost all inflammatory skin conditions (rashes) because the pathologist is able to examine both the superficial and deep portions of the dermis⁴ (FIGURE 2).

Pathologists use the pattern of inflammation, in conjunction with epidermal changes, to distinguish different types of inflammatory processes. For example, lichen planus is typically associated with superficial inflammation, while lupus is known to have prominent superficial and deep inflammation.

An inadequate punch biopsy sample can hinder histological assessment of inflammatory skin disorders that involve both the superficial and deep portions of the dermis and can make arriving at a definitive diagnosis more challenging. The diameter of a punch cylinder ranges from 1 to 8 mm. Smaller punch biopsies often create diagnostic challenges because they provide so little sample. A punch biopsy size of 4 mm is commonly used for rashes.

An advantage of the punch biopsy is that patients are left with linear scars rather than round, potentially dyspigmented (darker or lighter) scars that are often associated with shave biopsy. A well-sutured punch biopsy can be cosmetically elegant, particularly if closure is oriented along relaxed skin tension lines. For this reason, punch biopsies are well suited for cosmetically sensitive locations such as the face, although shave biopsies are also often performed on the face.

4. Choose an excisional biopsy for a melanocytic neoplasm, when possible.

The purpose of an excisional biopsy (which typically includes a 1 to 3 mm rim of normal skin around the lesion) is to completely remove a lesion. The excisional biopsy generally is the preferred technique for clinically atypical melanocytic neoplasms (lesions that are not definitively benign).^4-8

When suspicion for melanoma is high, excisional biopsies should be performed with minimal undermining to preserve the accuracy of any future sentinel lymph node biopsy surgeries. Excisional biopsy is the most involved type of biopsy and has the largest potential for cosmetic disfigurement if not properly planned and performed. While guidelines from the American Academy of Dermatology state that “narrow excisional biopsy that encompasses [the] entire breadth of lesion with clinically negative margins to ensure that the lesion is not transected” is preferred, they also acknowledge that partial sampling (incisional biopsy) is acceptable in select clinical circumstances,⁹ such as when a lesion is large or on a cosmetically sensitive site such as the face.¹⁰

While a larger punch biopsy (6 or 8 mm) or even deep shave/saucerization may function as an excisional biopsy for very small lesions, this approach can be problematic. For one thing, these biopsies are more likely than an excisional biopsy to leave a portion of the lesion in situ. Another concern is that a shave biopsy of a melanocytic lesion can lead to error or difficulty in obtaining the correct diagnosis on later biopsy.¹¹ For pathologists, smaller or incomplete samples make it challenging to establish an accurate diagnosis.¹² Among melanomas seen at a tertiary referral center, histopathological misdiagnosis was more common with a punch or shave biopsy than with an excisional biopsy.⁹

It has been shown that partial biopsy for melanoma results in more residual disease at wide local excision and makes it more challenging to properly stage the lesion.^13,14 If a shave biopsy is used to sample a suspected melanocytic neoplasm, it is imperative to document the specific site of the biopsy, indicate the size of the melanocytic lesion on the pathology requisition form, and ensure that all (or nearly all) of the clinically evident lesion is sampled. Detailing the location of the lesion in the chart is not only essential in evaluating the present lesion, but it will serve you well in the future. Without knowing the patient’s clinical history, benign nevi that recur after a prior biopsy can be difficult to histologically distinguish from melanoma (FIGURE 3). For more on this, see tip #7.

5. Be careful with curettage.

6. Remember the importance of proper fixation and processing.

As obvious as it may sound, it is important to remember to promptly place sampled tissue in an adequate amount of formalin so that the tissue is submersed in it in the container.¹⁵ Failure to do so can result in improper fixation and will make it difficult to render an appropriate diagnosis. Conventionally, a 10:1 formalin volume to tissue volume ratio is recommended. If the “cold time”—the amount of time a tissue sample is out of formalin—is long enough (greater than a few hours), an appropriate assessment can be impossible.

Appropriate fixation and fixation times are important because molecular testing is being increasingly used to make pathological diagnoses.¹⁶ Additionally, aggressively manipulating a biopsy sample while extracting it or placing it in formalin can cause “crush” artifact, which can limit interpretability (FIGURE 5).

7. Properly photograph and document the biopsy location.

When performing a biopsy of a suspicious neoplasm, physicians often remove all of the lesion’s superficial components, which means that at the patient’s follow-up appointment and subsequent treatments, only a well-healed biopsy site will remain. The biopsy site may be so well healed that it blends seamlessly into the surrounding skin and is nearly impossible for the physician to identify. This problem is seen most often when patients present for surgical excision or Mohs micrographic surgery.¹⁷

To properly record the site of a biopsy for future dermatologic exams, take pictures of the lesion at the time of biopsy. The photographs should clearly document the lesion in question, and should be taken far enough from the site that surrounding lesions and/ or other anatomic landmarks are also visible. Biangulation or triangulation (taking a series of 2 or 3 measurements, respectively, from the site of the lesion to nearby anatomic landmarks) can be used in conjunction with photographs.

When using measurements, be as specific and accurate as possible with anatomic terms. For example, measuring the distance from the “ear” is not helpful. It would be more helpful to measure the distance from the “tragus” or the “root of the helix.” Without a properly photographed and documented biopsy site, surgical treatment may need to be delayed until the location can be confirmed.

8. Give the pathologist a pertinent history.

Providing the pathologist with a sufficient history, including the distribution and appearance of the lesion, and how long the patient has had it, can be essential in narrowing the diagnosis or making the differential diagnoses. Things like medication use or new exposures to perfumes, lotions, or plants can be especially helpful and are often overlooked when filling out the pathology requisition form.

When warranted, phone calls are helpful. You might, for example, call the pathologist and give him or her a more detailed physical examination description or additional pertinent history that was discovered after the requisition was filled out. Providing a good history can make the difference between a specific diagnosis and a broad differential.

9. Know when to refer.


There is no shame in asking for a second opinion when it comes to evaluating a skin issue, especially in regards to melanocytic neoplasms, where the stakes can be high, or skin eruptions that do not respond to conventional therapy. Remember, many cases are difficult, even for experts, and require a careful balance of clinical and histopathological judgment.¹⁸

CORRESPONDENCE
Jayson Miedema, MD, Department of Dermatology, University of North Carolina at Chapel Hill, 410 Market Street, Suite 400, Chapel Hill, NC 27516; [email protected]

Most physicians do a satisfactory job in choosing when and how to do a skin biopsy, but there is always room for improvement. The 9 pointers we provide here are based on standard of care practices and literature when available, and also on our collective experiences as a pathologist/dermatologist (JM), dermatopathologist (DZ), primary care physician (BR), and dermatologist/Mohs surgeon (EB).

1. Choose your biopsy type wisely.

Using the appropriate type of biopsy can have the greatest effect on a proper diagnosis. The decision of which biopsy type to use is not always easy. The most common biopsy types are shave, punch, excisional, and curettage. Several reference articles detail each type of biopsy commonly used in primary care and how to perform them.^1,2 (For a series of how-to videos that illustrate how to perform some of these biopsies, visit The Journal of Family Practice Multimedia Library at http://www.jfponline.com/multimedia/video.html.)

Each type of biopsy has inherent advantages and disadvantages. In general, the shave biopsy is most commonly used for lesions that are solitary, elevated, and give the impression that a sufficient amount of tissue can be sampled using this technique. The punch biopsy is the biopsy of choice for most “rashes” (inflammatory skin disorders).² Excisional biopsy is used to remove melanocytic neoplasms or larger lesions. And curettage, while still used by some clinicians for melanocytic lesions because of its speed and simplicity, should almost never be used for diagnostic purposes. Each of these techniques is described in greater detail in the tips that follow.

2. When performing a shave biopsy, avoid obtaining a sample that's too superficial.

The advantage of the shave biopsy is that it is minimally invasive and quick to perform. If kept small while not compromising the amount of sample retrieved, the scars left by shave biopsies have the potential to blend well. The major disadvantage of the shave biopsy is that occasionally, if the shave is not deep enough, an insufficient amount of tissue is obtained, which can make it challenging to establish an accurate diagnosis.

An advantage 
of the punch biopsy is that patients are left with linear scars, rather than the round scars that are often associated with shave biopsy.Balancing the need to obtain adequate tissue while minimizing scarring takes skill and experience. Taking a biopsy that is inadequate is a common occurrence. At times, the physician’s clinical impression may be that a biopsy has obtained adequate tissue, but histologically only the superficial part of the skin surface has been sampled. This often is because of thickening of the superficial skin, whether as a manifestation of the anatomic site (eg, acral skin) or the disease process itself.

Unfortunately, this superficial skin often is nondiagnostic when unaccompanied by underlying epidermis and dermis. It is important to keep this in mind when obtaining a skin biopsy, especially when dealing with lesions that are very scaly or keratinized. An equivocal biopsy wastes time, energy, and money, and can negatively impact patient care.³ It can be difficult to balance practical aspects of the biopsy (ie, optimizing cosmetic outcomes, minimizing scarring and wound size) with the need to obtain sufficient tissue sampling (FIGURE 1).

3. Choose punch over shave biopsy for rashes.

In a punch biopsy, a disposable metal cylinder with a sharpened edge is used to “punch” out a piece of skin that can be examined under the microscope. Punch biopsy is the preferred technique for almost all inflammatory skin conditions (rashes) because the pathologist is able to examine both the superficial and deep portions of the dermis⁴ (FIGURE 2).

Pathologists use the pattern of inflammation, in conjunction with epidermal changes, to distinguish different types of inflammatory processes. For example, lichen planus is typically associated with superficial inflammation, while lupus is known to have prominent superficial and deep inflammation.

An inadequate punch biopsy sample can hinder histological assessment of inflammatory skin disorders that involve both the superficial and deep portions of the dermis and can make arriving at a definitive diagnosis more challenging. The diameter of a punch cylinder ranges from 1 to 8 mm. Smaller punch biopsies often create diagnostic challenges because they provide so little sample. A punch biopsy size of 4 mm is commonly used for rashes.

An advantage of the punch biopsy is that patients are left with linear scars rather than round, potentially dyspigmented (darker or lighter) scars that are often associated with shave biopsy. A well-sutured punch biopsy can be cosmetically elegant, particularly if closure is oriented along relaxed skin tension lines. For this reason, punch biopsies are well suited for cosmetically sensitive locations such as the face, although shave biopsies are also often performed on the face.

4. Choose an excisional biopsy for a melanocytic neoplasm, when possible.

The purpose of an excisional biopsy (which typically includes a 1 to 3 mm rim of normal skin around the lesion) is to completely remove a lesion. The excisional biopsy generally is the preferred technique for clinically atypical melanocytic neoplasms (lesions that are not definitively benign).^4-8

When suspicion for melanoma is high, excisional biopsies should be performed with minimal undermining to preserve the accuracy of any future sentinel lymph node biopsy surgeries. Excisional biopsy is the most involved type of biopsy and has the largest potential for cosmetic disfigurement if not properly planned and performed. While guidelines from the American Academy of Dermatology state that “narrow excisional biopsy that encompasses [the] entire breadth of lesion with clinically negative margins to ensure that the lesion is not transected” is preferred, they also acknowledge that partial sampling (incisional biopsy) is acceptable in select clinical circumstances,⁹ such as when a lesion is large or on a cosmetically sensitive site such as the face.¹⁰

While a larger punch biopsy (6 or 8 mm) or even deep shave/saucerization may function as an excisional biopsy for very small lesions, this approach can be problematic. For one thing, these biopsies are more likely than an excisional biopsy to leave a portion of the lesion in situ. Another concern is that a shave biopsy of a melanocytic lesion can lead to error or difficulty in obtaining the correct diagnosis on later biopsy.¹¹ For pathologists, smaller or incomplete samples make it challenging to establish an accurate diagnosis.¹² Among melanomas seen at a tertiary referral center, histopathological misdiagnosis was more common with a punch or shave biopsy than with an excisional biopsy.⁹

It has been shown that partial biopsy for melanoma results in more residual disease at wide local excision and makes it more challenging to properly stage the lesion.^13,14 If a shave biopsy is used to sample a suspected melanocytic neoplasm, it is imperative to document the specific site of the biopsy, indicate the size of the melanocytic lesion on the pathology requisition form, and ensure that all (or nearly all) of the clinically evident lesion is sampled. Detailing the location of the lesion in the chart is not only essential in evaluating the present lesion, but it will serve you well in the future. Without knowing the patient’s clinical history, benign nevi that recur after a prior biopsy can be difficult to histologically distinguish from melanoma (FIGURE 3). For more on this, see tip #7.

5. Be careful with curettage.

6. Remember the importance of proper fixation and processing.

As obvious as it may sound, it is important to remember to promptly place sampled tissue in an adequate amount of formalin so that the tissue is submersed in it in the container.¹⁵ Failure to do so can result in improper fixation and will make it difficult to render an appropriate diagnosis. Conventionally, a 10:1 formalin volume to tissue volume ratio is recommended. If the “cold time”—the amount of time a tissue sample is out of formalin—is long enough (greater than a few hours), an appropriate assessment can be impossible.

Appropriate fixation and fixation times are important because molecular testing is being increasingly used to make pathological diagnoses.¹⁶ Additionally, aggressively manipulating a biopsy sample while extracting it or placing it in formalin can cause “crush” artifact, which can limit interpretability (FIGURE 5).

7. Properly photograph and document the biopsy location.

When performing a biopsy of a suspicious neoplasm, physicians often remove all of the lesion’s superficial components, which means that at the patient’s follow-up appointment and subsequent treatments, only a well-healed biopsy site will remain. The biopsy site may be so well healed that it blends seamlessly into the surrounding skin and is nearly impossible for the physician to identify. This problem is seen most often when patients present for surgical excision or Mohs micrographic surgery.¹⁷

To properly record the site of a biopsy for future dermatologic exams, take pictures of the lesion at the time of biopsy. The photographs should clearly document the lesion in question, and should be taken far enough from the site that surrounding lesions and/ or other anatomic landmarks are also visible. Biangulation or triangulation (taking a series of 2 or 3 measurements, respectively, from the site of the lesion to nearby anatomic landmarks) can be used in conjunction with photographs.

When using measurements, be as specific and accurate as possible with anatomic terms. For example, measuring the distance from the “ear” is not helpful. It would be more helpful to measure the distance from the “tragus” or the “root of the helix.” Without a properly photographed and documented biopsy site, surgical treatment may need to be delayed until the location can be confirmed.

8. Give the pathologist a pertinent history.

Providing the pathologist with a sufficient history, including the distribution and appearance of the lesion, and how long the patient has had it, can be essential in narrowing the diagnosis or making the differential diagnoses. Things like medication use or new exposures to perfumes, lotions, or plants can be especially helpful and are often overlooked when filling out the pathology requisition form.

When warranted, phone calls are helpful. You might, for example, call the pathologist and give him or her a more detailed physical examination description or additional pertinent history that was discovered after the requisition was filled out. Providing a good history can make the difference between a specific diagnosis and a broad differential.

9. Know when to refer.


There is no shame in asking for a second opinion when it comes to evaluating a skin issue, especially in regards to melanocytic neoplasms, where the stakes can be high, or skin eruptions that do not respond to conventional therapy. Remember, many cases are difficult, even for experts, and require a careful balance of clinical and histopathological judgment.¹⁸

CORRESPONDENCE
Jayson Miedema, MD, Department of Dermatology, University of North Carolina at Chapel Hill, 410 Market Street, Suite 400, Chapel Hill, NC 27516; [email protected]

Most physicians do a satisfactory job in choosing when and how to do a skin biopsy, but there is always room for improvement. The 9 pointers we provide here are based on standard of care practices and literature when available, and also on our collective experiences as a pathologist/dermatologist (JM), dermatopathologist (DZ), primary care physician (BR), and dermatologist/Mohs surgeon (EB).

1. Choose your biopsy type wisely.

Using the appropriate type of biopsy can have the greatest effect on a proper diagnosis. The decision of which biopsy type to use is not always easy. The most common biopsy types are shave, punch, excisional, and curettage. Several reference articles detail each type of biopsy commonly used in primary care and how to perform them.^1,2 (For a series of how-to videos that illustrate how to perform some of these biopsies, visit The Journal of Family Practice Multimedia Library at http://www.jfponline.com/multimedia/video.html.)

Each type of biopsy has inherent advantages and disadvantages. In general, the shave biopsy is most commonly used for lesions that are solitary, elevated, and give the impression that a sufficient amount of tissue can be sampled using this technique. The punch biopsy is the biopsy of choice for most “rashes” (inflammatory skin disorders).² Excisional biopsy is used to remove melanocytic neoplasms or larger lesions. And curettage, while still used by some clinicians for melanocytic lesions because of its speed and simplicity, should almost never be used for diagnostic purposes. Each of these techniques is described in greater detail in the tips that follow.

2. When performing a shave biopsy, avoid obtaining a sample that's too superficial.

The advantage of the shave biopsy is that it is minimally invasive and quick to perform. If kept small while not compromising the amount of sample retrieved, the scars left by shave biopsies have the potential to blend well. The major disadvantage of the shave biopsy is that occasionally, if the shave is not deep enough, an insufficient amount of tissue is obtained, which can make it challenging to establish an accurate diagnosis.

An advantage 
of the punch biopsy is that patients are left with linear scars, rather than the round scars that are often associated with shave biopsy.Balancing the need to obtain adequate tissue while minimizing scarring takes skill and experience. Taking a biopsy that is inadequate is a common occurrence. At times, the physician’s clinical impression may be that a biopsy has obtained adequate tissue, but histologically only the superficial part of the skin surface has been sampled. This often is because of thickening of the superficial skin, whether as a manifestation of the anatomic site (eg, acral skin) or the disease process itself.

Unfortunately, this superficial skin often is nondiagnostic when unaccompanied by underlying epidermis and dermis. It is important to keep this in mind when obtaining a skin biopsy, especially when dealing with lesions that are very scaly or keratinized. An equivocal biopsy wastes time, energy, and money, and can negatively impact patient care.³ It can be difficult to balance practical aspects of the biopsy (ie, optimizing cosmetic outcomes, minimizing scarring and wound size) with the need to obtain sufficient tissue sampling (FIGURE 1).

3. Choose punch over shave biopsy for rashes.

In a punch biopsy, a disposable metal cylinder with a sharpened edge is used to “punch” out a piece of skin that can be examined under the microscope. Punch biopsy is the preferred technique for almost all inflammatory skin conditions (rashes) because the pathologist is able to examine both the superficial and deep portions of the dermis⁴ (FIGURE 2).

Pathologists use the pattern of inflammation, in conjunction with epidermal changes, to distinguish different types of inflammatory processes. For example, lichen planus is typically associated with superficial inflammation, while lupus is known to have prominent superficial and deep inflammation.

An inadequate punch biopsy sample can hinder histological assessment of inflammatory skin disorders that involve both the superficial and deep portions of the dermis and can make arriving at a definitive diagnosis more challenging. The diameter of a punch cylinder ranges from 1 to 8 mm. Smaller punch biopsies often create diagnostic challenges because they provide so little sample. A punch biopsy size of 4 mm is commonly used for rashes.

An advantage of the punch biopsy is that patients are left with linear scars rather than round, potentially dyspigmented (darker or lighter) scars that are often associated with shave biopsy. A well-sutured punch biopsy can be cosmetically elegant, particularly if closure is oriented along relaxed skin tension lines. For this reason, punch biopsies are well suited for cosmetically sensitive locations such as the face, although shave biopsies are also often performed on the face.

4. Choose an excisional biopsy for a melanocytic neoplasm, when possible.

The purpose of an excisional biopsy (which typically includes a 1 to 3 mm rim of normal skin around the lesion) is to completely remove a lesion. The excisional biopsy generally is the preferred technique for clinically atypical melanocytic neoplasms (lesions that are not definitively benign).^4-8

When suspicion for melanoma is high, excisional biopsies should be performed with minimal undermining to preserve the accuracy of any future sentinel lymph node biopsy surgeries. Excisional biopsy is the most involved type of biopsy and has the largest potential for cosmetic disfigurement if not properly planned and performed. While guidelines from the American Academy of Dermatology state that “narrow excisional biopsy that encompasses [the] entire breadth of lesion with clinically negative margins to ensure that the lesion is not transected” is preferred, they also acknowledge that partial sampling (incisional biopsy) is acceptable in select clinical circumstances,⁹ such as when a lesion is large or on a cosmetically sensitive site such as the face.¹⁰

While a larger punch biopsy (6 or 8 mm) or even deep shave/saucerization may function as an excisional biopsy for very small lesions, this approach can be problematic. For one thing, these biopsies are more likely than an excisional biopsy to leave a portion of the lesion in situ. Another concern is that a shave biopsy of a melanocytic lesion can lead to error or difficulty in obtaining the correct diagnosis on later biopsy.¹¹ For pathologists, smaller or incomplete samples make it challenging to establish an accurate diagnosis.¹² Among melanomas seen at a tertiary referral center, histopathological misdiagnosis was more common with a punch or shave biopsy than with an excisional biopsy.⁹

It has been shown that partial biopsy for melanoma results in more residual disease at wide local excision and makes it more challenging to properly stage the lesion.^13,14 If a shave biopsy is used to sample a suspected melanocytic neoplasm, it is imperative to document the specific site of the biopsy, indicate the size of the melanocytic lesion on the pathology requisition form, and ensure that all (or nearly all) of the clinically evident lesion is sampled. Detailing the location of the lesion in the chart is not only essential in evaluating the present lesion, but it will serve you well in the future. Without knowing the patient’s clinical history, benign nevi that recur after a prior biopsy can be difficult to histologically distinguish from melanoma (FIGURE 3). For more on this, see tip #7.

5. Be careful with curettage.

6. Remember the importance of proper fixation and processing.

As obvious as it may sound, it is important to remember to promptly place sampled tissue in an adequate amount of formalin so that the tissue is submersed in it in the container.¹⁵ Failure to do so can result in improper fixation and will make it difficult to render an appropriate diagnosis. Conventionally, a 10:1 formalin volume to tissue volume ratio is recommended. If the “cold time”—the amount of time a tissue sample is out of formalin—is long enough (greater than a few hours), an appropriate assessment can be impossible.

Appropriate fixation and fixation times are important because molecular testing is being increasingly used to make pathological diagnoses.¹⁶ Additionally, aggressively manipulating a biopsy sample while extracting it or placing it in formalin can cause “crush” artifact, which can limit interpretability (FIGURE 5).

7. Properly photograph and document the biopsy location.

When performing a biopsy of a suspicious neoplasm, physicians often remove all of the lesion’s superficial components, which means that at the patient’s follow-up appointment and subsequent treatments, only a well-healed biopsy site will remain. The biopsy site may be so well healed that it blends seamlessly into the surrounding skin and is nearly impossible for the physician to identify. This problem is seen most often when patients present for surgical excision or Mohs micrographic surgery.¹⁷

To properly record the site of a biopsy for future dermatologic exams, take pictures of the lesion at the time of biopsy. The photographs should clearly document the lesion in question, and should be taken far enough from the site that surrounding lesions and/ or other anatomic landmarks are also visible. Biangulation or triangulation (taking a series of 2 or 3 measurements, respectively, from the site of the lesion to nearby anatomic landmarks) can be used in conjunction with photographs.

When using measurements, be as specific and accurate as possible with anatomic terms. For example, measuring the distance from the “ear” is not helpful. It would be more helpful to measure the distance from the “tragus” or the “root of the helix.” Without a properly photographed and documented biopsy site, surgical treatment may need to be delayed until the location can be confirmed.

8. Give the pathologist a pertinent history.

Providing the pathologist with a sufficient history, including the distribution and appearance of the lesion, and how long the patient has had it, can be essential in narrowing the diagnosis or making the differential diagnoses. Things like medication use or new exposures to perfumes, lotions, or plants can be especially helpful and are often overlooked when filling out the pathology requisition form.

When warranted, phone calls are helpful. You might, for example, call the pathologist and give him or her a more detailed physical examination description or additional pertinent history that was discovered after the requisition was filled out. Providing a good history can make the difference between a specific diagnosis and a broad differential.

9. Know when to refer.


There is no shame in asking for a second opinion when it comes to evaluating a skin issue, especially in regards to melanocytic neoplasms, where the stakes can be high, or skin eruptions that do not respond to conventional therapy. Remember, many cases are difficult, even for experts, and require a careful balance of clinical and histopathological judgment.¹⁸

CORRESPONDENCE
Jayson Miedema, MD, Department of Dermatology, University of North Carolina at Chapel Hill, 410 Market Street, Suite 400, Chapel Hill, NC 27516; [email protected]