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When Should You Biopsy?

When facing a skin condition or wound that can be challenging to identify, a biopsy can be an invaluable tool in illuminating a path for diagnosis and treatment. This author details the protocol for when to perform a biopsy and which technique to choose for which clinical presentation.

As many skin conditions are clinically difficult to differentiate, a biopsy provides a histopathologic diagnosis that ultimately helps to support the treatment plan. It can also clarify the skin disorder when a treatment plan is not yielding the appropriate results. Lastly, a biopsy can be curative or even life saving if one excises the lesion in toto or when the biopsy helps identify a treatable malignant diagnosis. Ultimately, a biopsy can both complement and confirm the diagnosis.

   Over the last few years, our profession has been exposed to biopsy workshops and lectures at numerous conferences. The techniques of performing shave, punch and incisional/excisional biopsies are fairly straightforward, but when you return to the office on Monday after that weekend conference, are you confident which lesions to choose and when to perform those techniques?

   Accordingly, I would like to present a basic guideline you can use in daily practice when confronting challenging wounds, rashes and pigmented lesions.

Biopsies For Wounds: What You Should Know

Understanding the etiology of a wound is imperative in its management. Besides establishing a diagnosis, one of the most important reasons for performing a wound biopsy is to rule out the presence of malignancy. Chronic wounds that are the site of longstanding inflammation, such as from a burn or a sinus tract, may transform into malignant lesions. A squamous cell carcinoma arising in an area of an old scar, burn or wound is termed a Marjolin’s ulcer and occurs more often in the lower extremity.1 This transformational process may take anywhere from one year to 25 years to develop.2 In addition, lesions that are malignant (both de novo and metastasis) may present as wounds and one can easily misdiagnose them as chronic wounds.

   When should you biopsy a wound?

• The treated area has been present for over three months and has not responded to standard treatment.
• The wound bed has become exophytic and hypergranular.
• In the absence of infection, the wound has become painful, malodorous and the amount of drainage has changed.3

   For the clinician who works in a wound care center, consider the scenario of a patient who presents with a painful medial leg ulcer that has been present for 25 years, has received treatment for a venous stasis ulcer and has not seen any changes with the ulcer. This is suggestive of performing a biopsy during the first visit. After performing a thorough history and physical, the clinician may perform a wound biopsy to rule out malignancy, but also to determine if the wound has an inflammatory basis. Painful leg wounds, such as pyoderma gangrenosum, arising in the presence of rheumatoid arthritis, inflammatory bowel disease or hematological disorders may not have specific histopathologic identifiers in their chronic state. In the case of pyoderma gangrenosum, this diagnosis of exclusion can be just as helpful to facilitate an appropriate treatment course for the patient.

   Other inflammatory based ulcers include those that occur with vasculitis, anticoagulant syndromes and drug reactions. In those cases, it might be helpful to do a second biopsy and send the sample for direct immunofluorescence, which will help in elucidating the underlying cause.

   When performing a biopsy for a suspected basal cell carcinoma or squamous cell carcinoma, one may perform a deep punch or incisional biopsy of the base and the wound edge.3 For pyoderma gangrenosum, two biopsies (punch or incisional) that include the wound edge (with partial ulcer bed) and the central base will be useful. When an ulcer is associated with vasculitis, the center of the lesion is best to biopsy but a punch of newly formed palpable purpura would also be diagnostic. One should send a specimen for direct immunofluorescence staining in a special media (Michel’s fixative) and the pathology lab of choice can assist the clinician in obtaining a kit for easy transport. Otherwise, one should send all other specimens for histopathology in 10% formalin solution.

   Overall, one should obtain a sample of a wound that has not decreased in size after several months of standard care, has changed in a negative manner, has a suspected etiology beyond the original diagnosis and has a potential for being malignant. Send this sample for a histopathologic review.

When Rashes Do Not Seem To Respond To Treatment

All of us have experienced a patient whose red, scaly rash has not responded to our prescription topical therapy. Not only is this challenging to us as practitioners but also to the patient. Failure to respond to conventional therapy warrants a skin biopsy.

   In these cases, a punch biopsy is an appropriate choice. I have also utilized this procedure in patients who have seen numerous practitioners prior to a visit with me, have a long list of failed medications and have not had a skin biopsy to define the skin condition. In these cases, I choose to perform the skin biopsy prior to initiating any further treatment in order to refine my management plan and reduce the patient’s frustration of purchasing yet another possible failed therapy.

   I do not recommend routine biopsy of all skin rashes. However, if a new onset rash does not correspond to the conventional presentations of psoriasis, eczema and lichen planus, a punch biopsy can be a useful diagnostic tool (see the table “A Closer Look At Biopsy Recommendations For Inflammatory Skin Conditions” above at right). In the case of a psoriatic-like plaque, differential diagnoses can range from plaque psoriasis to cutaneous T-cell lymphoma. Treatment plans for these two diagnoses vary in approach and prognosis.

When To Biopsy Suspicious Pigmented Lesions

Over the course of a career, the podiatric practitioner will face diagnosing benign lesions (nevi, dermatofibroma), pre-cancerous lesions (actinic keratosis), non-melanoma skin cancer (basal cell and squamous cell) and melanoma (see the table “A Guide To Biopsies For Pigmented Lesions” below at right).

   When facing a pigmented lesion, it is important first to establish if the lesion is melanocytic. Examples of melanocytic lesions are nevi, lentigines, atypical nevi and melanoma. Early detection of a melanoma is ideal but choosing which melanocytic lesion to biopsy can be difficult. A biopsy of every pigmented lesion on a patient would be “disfiguring and unnecessary.”4 The combination of clinical examination and choosing the appropriate biopsy type for the lesion can aid in diagnosis and management.

   After performing a thorough history and physical exam, and prior to the biopsy, one may consider adding dermoscopy and confocal microscopy to the exam when trying to determine if and where to biopsy. Dermoscopy requires special instrumentation and education, but it is a valuable technique in refining the decision of whether or not to biopsy. As with any technique, there are limitations and the dermoscopy exam can yield questionable and vague results.

   Therefore, the in vivo reflectance confocal microscope is a tool that physicians increasingly use to evaluate pigmented lesions. The microscope works in a similar principle to ultrasound but instead of sound waves, it uses laser optics to visualize melanocytic lesions. The confocal microscope is mainly in use in large academic medical centers and is a valuable resource for dermatologists specializing in identifying and managing pigmented lesions.

Key Questions To Ask For The Patient History

Beyond these advanced instruments available to specialists, it is still important to ask the patient pertinent questions regarding the lesion, look at the lesion carefully and then biopsy when appropriate to have the best overall outcome.

   What questions should the clinician ask of patients with a suspicious lesion?

• Has the lesion changed? If so, how has it changed?
• Did the lesion develop after the patient was over the age of 40?
• Is the lesion pruritic?
• Is the lesion in a previous (or current) site of a nevi, ulcer or scar?
• Has the lesion failed to heal?

   For lesions that have not healed despite conventional therapies, one should obtain a biopsy to rule out a malignant process.

Pertinent Insights On The ABCs Of Melanoma

Following the patient interview, the clinician should subsequently perform the exam utilizing the ABCs of melanoma and the “ugly duckling” sign. The ABCs of melanoma are a guide when investigating a suspicious melanocytic lesion.

A–Asymmetry. One side of the lesion is different from the other side.

B–Border. Notching and irregularity are uncommon in benign lesions.

C-Color. Shades of red, white and blue along with black may indicate a superficial spreading melanoma type.

D-Diameter. Lesions under 6 mm in diameter are more likely to be benign.

E–Evolving. Any changing mole warrants careful observation and probable biopsy.

F-Family or personal history of skin cancer.

   The ABCs of subungual melanoma are as follows:

A-Age (fifth to seventh decade is peak)

B-Brown to black discoloration with a breadth of 3 mm or greater

C-Change in the nail plate or lack of change with treatment

D-Digit most commonly affected (hallux)

E-Extension of pigment into proximal nail fold or lateral nail fold (Hutchinson’s sign)

F-Family or personal history of skin cancer

   The “ugly duckling” sign is also relevant. Most nevi in an individual tend to resemble each other. One should view with suspicion a melanocytic lesion that appears grossly different from the others. Both of these visual techniques are guides and are not perfect. However, they are solid places to begin the decision making process of whether or not to biopsy a lesion.

   If you have used the ABCs of melanoma and the “ugly duckling” sign as guidelines and still have doubts about a lesion, I recommend a referral to a dermatologist.

   After making the determination to sample a suspicious pigmented lesion, the clinician should determine the type of biopsy to occur. The American Academy of Dermatology and National Comprehensive Cancer Network have suggested, when possible, to perform a total excisional biopsy (see the table “What The National Comprehensive Cancer Network And The American Academy Of Dermatology Recommend For Biopsies” at right). Fully realizing that larger lesions and various anatomical areas (soles, digits, subungual) are not always amenable to a total excision with a 1 to 3 mm border, their recommendations then include incisional and punch biopsies. They reserve a deep shave technique for when the index of suspicion for melanoma is low to none.

   Throughout the years, clinicians have shared the concern of creating metastasis during the initial biopsy procedure of a melanocytic lesion. Various studies have been unable to show differences in survival and sentinel lymph node metastasis between those who had an excisional procedure versus those who had an incisional, punch or deep shave biopsy procedure.4 The major concern that the National Comprehensive Cancer Network and American Academy of Dermatology have regarding the non-excisional procedures is the possible lack of procuring the deep margin of the tumor. The deep margin helps to determine the Breslow’s depth, which allows for staging of the lesion and ultimately the prognosis. Ultimately, the guidelines recommend excision when possible and non-excisional biopsy of an area that best represents the lesion in difficult anatomic areas and large lesions.4

Final Words

In general, choosing when to biopsy can prove to be a challenge to the practitioner. After a thorough history and clinical examination, the clinician needs not only to choose which lesion to biopsy, but also what type of biopsy to perform. Overall, a wound, rash or lesion that does not meet general criteria should have a biopsy. Also, regard a lesion that hasn’t responded to standard therapy with suspicion and obtain a sample.

   In conclusion, biopsy of these aforementioned conditions is a valuable technique that allows the practitioner to refine a diagnosis and direct the further course of treatment.

   Dr. Vlahovic is an Associate Professor and J. Stanley and Pearl Landau Fellow at the Temple University School of Podiatric Medicine.

1. Cocchetto V, Magrin P, de Paula RA, et al. Squamous cell carcinoma in chronic wound: Marjolin ulcer. Dermatol Online J. 2013; 19(2):7.
2. Pavlovic S, Wiley E, Guzman G, et al. Marjolin ulcer: an overlooked entity. Int Wound J. 2011; 8(4):419-24.
3. Alavi A, Niakosari F, Sibbald RG. When and how to perform a biopsy on a chronic wound. Adv Skin Wound Care. 2010; 23(3):132.
4. Tran KT, Wright NA, Cockerell CJ. Biopsy of the pigmented lesion-When and how. J Am Acad Dermatol. 2008; 59(5):852-71.
5. Sina B, Kao G, Deng A, Gaspari A. Skin biopsy for inflammatory and common neoplastic skin diseases: optimum time, best location, and preferred techniques. A critical review. J Cutan Pathol. 2009; 36(5):505-10.

Tracey C. Vlahovic, DPM
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