Cutaneous malignancies and benign neoplasms simulating malignancy commonly affect the distal lower extremity, including the foot. One may see a variety of malignancy categories such as epithelial tumors, adnexal neoplasms, melanoytic neoplasms, vascular neoplasms and soft tissue tumors. Histologic confirmation of diagnosis is essentially mandatory, warranting the need to send all tissue specimens, including biopsy, incisional and excisional specimens, for pathology examination. In some cases, the pathologist may incorporate immunohistochemical stains to differentiate specific tumor types. Developing and maintaining a close working relationship with a pathologist who is board-certified or highly skilled in dermatopathology is very helpful in optimizing clinical and histologic correlation in order to maximize diagnostic accuracy. With this in mind, let’s take a closer look at three cases in which skin malignancy or clinical simulants affect the distal lower extremity. Case One Presentation: A Firm, Slow-Growing Exophytic Nodule A 46-year-old Caucasian male presented with a six-month history of a slowly growing, firm, well-defined, exophytic and asymptomatic nodule measuring 1.2 cm in diameter (see below photo). The lesion was on the proximal plantar surface. Approximately three months prior to presentation, the patient self-treated the lesion (which he thought was a wart) for two weeks with a topical salicylic acid 17% liquid. There was no response. The major neoplasms in this differential diagnosis include pyogenic granuloma, amelanotic melanoma, squamous cell carcinoma and eccrine poroma. In this case, obtaining an excisional biopsy is preferable. Unless you have a clinical suspicion of melanoma, you may also obtain a deep saucerization biopsy, which encompasses the breadth of the neoplasm and is respresentative of its deeper aspect. The histologic evaluation confirmed eccrine poroma. Eccrine poroma is a benign tumor which arises from eccrine glands, which are sweat glands naturally found in high concentration on the palms and soles.1,2 This type of tumor may simulate other malignant or benign tumors as mentioned above in the differential diagnosis. Eccrine poromas are typically solitary. They are usually slightly pedunculated or surrounded by a keratotic collarette. You will often see them on the plantar or lateral surface of the foot and they are usually less than 2 cm in diameter.1,2 The treatment of eccrine poroma is surgical excision with clear pathologic margins in order to reduce the risk of recurrence. The presence of multiple small eccrine poroma papules on the palms and soles (eccrine poromatosis) is an unusual and very rare presentation.3 Although relatively uncommon, malignant eccrine poroma (porocarcinoma), arising within a long-standing eccrine poroma, may remain localized or may metastasize, usually forming multiple cutaneous metastases with possible associated visceral metastases.4,5 Due to the absence of melanotic pigment, amelanotic melanoma may look similar to eccrine poroma, as may a nodular form of squamous cell carcinoma. Pyogenic granuloma, also referred to as lobular capillary hemangioma, is a benign proliferative angiomatous neoplasm, which tends to develop and grow rapidly over a period of a few weeks (see photo at right).6 The lesion may be pedunculated or associated with an epidermal collarette. Occurring anywhere on the cutaneous surface, including the feet, pyogenic granuloma usually has a red, vascular appearance and may be friable with easy bleeding. Case Two Presentation: Large Erythematous Plaques A 62-year-old female presented with two large, erythematous scaly asymptomatic plaques on the medial surface of her leg (see below photo at left). The lesions started smaller and slowly expanded in radial diameter over the course of at least eight years. Previous treatment with a topical antifungal (econazole) cream for approximately one month produced no change. Subsequent treatment with a high potency topical corticosteroid for three weeks also produced no response. The patient did not have any other similar lesions and there was no regional adenopathy upon palpation. Given the appearance of the lesion, clinical considerations include squamous cell carcinoma in situ (Bowen’s Disease), psoriasis vulgaris, nummular eczema, tinea corporis and superficial basal cell carcinoma. The complete lack of response to treatment suggests against nummular eczema and tinea corporis. A negative potassium hydroxide (KOH) preparation and fungal culture could also assist in excluding fungal infection. In addition, the lack of pruritus would seem to exclude, on clinical grounds, an eczematous process such as nummular (coin-shaped) eczema. The surface scaling is somewhat hyperkeratotic and doesn’t resemble the typical silver micaceous scaling of psoriasis. However, be aware that recent topical corticosteroid therapy may alter the clinical appearance of psoriasis. The clinical presentation favors squamous cell carcinoma in situ due to the sharply defined border, irregular outline of the plaques, the lack of symptomatology, pink erythema and scattered hyperkeratotic surface change. A histologic evaluation of a broad saucerization specimen confirmed this diagnosis. Also keep in mind that superficial basal cell carcinoma may present with a very similar clinical appearance to squamous cell carcinoma in situ (see below photo). Squamous cell carcinoma in situ is a superficial form of squamous cell carcinoma with histologic features limited to full-thickness epidermal involvement without violation of the basement membrane.7,8 The most common inciting factor is chronic ultraviolet radiation exposure, usually from sunlight. While this condition can develop on any area of skin, involvement of the legs is relatively common, especially in females. Lesions of squamous cell carcinoma-in-situ tend to grow very slowly. Progression to invasive squamous cell carcinoma occurs in up to 10 percent of cases, usually occurring after a delay of several years.9 Many cases arise from small precancerous foci called actinic keratoses. Weighing The Treatment Options Depending on the size and anatomic location of the lesion, one’s treatment options include curretage, temperature-monitored cryotherapy, surgical excision (including micrographic surgery to examine for margin clearance) and radiation therapy.10 Topical 5-fluorouracil has also been recommended. However, the consistency of this approach in terms of tumor clearance of squamous cell carcinoma in situ remains unconfirmed. Although topical imiquimod is not currently approved by the Food and Drug Administration (FDA) for this indication, multiple reports have shown it to be effective in treating squamous cell carcinoma in situ.11 In this patient, due to the large lesion size and its presence on the leg, radiation therapy is a very viable option. Case Three Presentation: Rapid Growth Of An Erythematous Nodule Within A Preexisting Mole A 56-year-old male presented with a 1cm erythematous nodule on the proximal dorsum of the left foot (see below photo). The nodule had grown rapidly over a period of six to eight weeks. The patient had difficulty expressing himself verbally due to a previous cerebral vascular accident. His wife related that the lesion grew within a preexisting dark brown “mole” which was present for several years. The wife indicated that the patient’s mother told her several years ago that the mole was present since birth. The lesion was not symptomatic. There was no regional adenopathy noted upon palpation. The clinical appearance is highly characteristic of a melanoma with a large central nodule, possibly arising within a congenital nevus. An excisional biopsy confirmed the diagnois. The reported histologic features were Clark’s Level IV, Breslow thickness 4.5 mm with surface ulceration, no evidence of regression and no microsatellites. The patient had a contiguous melanocytic nevus consistent with a pre-existing congenital nevus. When patients have lesions suggestive of melanoma, it is recommended that you obtain an excisional biopsy inclusive of a surrounding rim of 2 to 5 mm of normal tissue.12 With very large clinical lesions, one may consider a full-thickness fusiform incisional biopsy, inclusive of as large a specimen from the lesion as possible. When completing an incisional biopsy, it is important to include the thickest portion of the lesion based on palpation. Key Diagnostic Markers In order to help ensure the highest degree of accuracy in the histologic diagnosis of melanoma, make sure the entire breadth of the lesion is available for examination. Also be aware that additional treatment, work-up for staging and prognosis are dependent on the depth of invasion reported on the pathology report. The Clark’s level is an anatomic measurement while the Breslow thickness is a numerical measurement reported in millimeters.13 If the Breslow thickness is below 1 mm, the risk of metastasis is less than 5 percent after excisional surgery using 1 cm surgical margins. As a result, it is important to avoid partial thickness biopsy procedures (i.e. shave, saucerization) or small incisional biopsy procedures (i.e. punch biopsy) as they often do not provide enough tissue to establish a correct diagnosis or proper assessment of the depth of invasion. As the Breslow thickness increases, metastatic potential also increases. When there is a Breslow thickness beyond 4 mm, there is a reasonable likelihood that regional and/or systemic metastasis has occurred, even though it may not be clinically evident yet. In this case, additional surgical removal is warranted, preferably with surgical margins of 2 to 3 cm if it is clinically feasible.14 Essential Insights On Treatment And Follow-Up Overall, current evidence does not suggest definitive benefit from elective regional lymph node dissection. Sentinel lymph node lymphoscintigraphy with directed node biopsy may be helpful in determining whether regional lymph node metastasis has occurred.15 When it comes to melanoma, one should make the appropriate referral to specialists skilled in the treatment, nuances of patient evaluation, staging and use of adjunctive therapies for the condition. This is especially the case when patients have lesions demonstrating a Breslow thickness greater than 1 mm or other concerning histologic features (i.e. ulceration, regression, microscopic satellites, etc.). Long-term follow-up is indicated after treatment to evaluate for possible recurrence, metastasis or the development of a second primary melanoma. Clinical features of melanoma are asymmetry of a given lesion, border irregularity (i.e. notching), color variation within a given lesion, a greater than 6 mm diameter and a raised surface texture. These features are commonly referred to as the ABCDEs of melanoma, but remember that not all features need to be present to raise the index of suspicion. Patients should be encouraged to perform monthly self-examination of their skin and report any changes in preexisting lesions (“moles”) or newly developing “spots” or “growths” on their skin. Interestingly, acral melanoma (acral lentiginous melanoma) involving the palms, soles or periungual region represents up to 70 percent of melanomas in individuals with dark complexions (i.e. African-Americans) and up to 45 percent in Asian individuals.15 For example, one 38-year-old female presented with a melanoma on the lateral lower leg (see below photo). The melanoma presented as a slightly raised plaque measuring 1.1 cm in diameter with border irregularity. Upon careful inspection, one can note color variation with a lighter brown rim comprising the periphery of the lesion. The development of melanoma within congenital nevi has long been recognized. The potential risk is unknown and appears to be higher in larger congenital nevi greater than 20 cm.15 Overall, the development of melanoma within congenital nevi is believed to be uncommon. However, when one considers the total number of small and large congenital nevi, melanomas do occasionally arise within smaller congenital nevi. While the point in time when this may occur is variable and unpredictable, they most commonly develop at some point after puberty. Therefore, if you see a congenital nevus during the physical examination and the patient says the lesion has not changed, it is important to discuss the options, benefits and potential risks of prophylactic surgical excision as opposed to you and the patient watching the lesion over time for any visible or symptomatic changes. Dr. Del Rosso is a Clinical Assistant Professor within the Department of Dermatology at the University of Nevada School of Medicine in Las Vegas. CE Exam #112 Choose the single best response to each question listed below: 1. Eccrine poroma is most commonly located: a) at the base of the large toe b) at the free edge of the toenail (hyponychium) c) on the plantar of lateral surface of the foot d) none of the above 2. Pyogenic granuloma is also referred to as: a) epidermotropic hemangioma b) lobular capillary hemangioma c) granuloma infantum d) none of the above 3. Which of the following is not a treatment option for squamous cell carcinoma in situ? a) radiation therapy b) surgical excision c) topical tacrolimus d) topical imiquimod 4. Squamous cell carcinoma-in situ has been reported to progress to invasive squamous cell carcinoma in: a) up to 75 percent of cases b) up to 50 percent of cases c) up to 10 percent of cases d) none of the above 5. The most common etiologic factor associated with the development of Bowen’s disease is: a) exposure to topical nitrogen mustard b) ingestion of arsenic c) human papillomavirus infection d) chronic exposure to ultraviolet light 6. Which of the following is not true with regard to melanoma? a) they do not ever arise within congenital nevi b) they may have irregular borders c) they may be associated with a change in surface texture d) they may have color variation 7. Which of the following is an important histologic factor for prognosis in a patient with melanoma? a) Breslow thickness b) extent of color variation c) extent of visible asymmetry d) measurable width on the skin surface 8. Up to 45 percent of melanomas occurring in Asian patients are: a) nodular b) congenital c) acral lentiginous d) ulcerative 9. The best method of biopsy for a skin lesion suspicious for melanoma is: a) punch b) shave c) saucerization d) excisional 10. The greater the Breslow thickness: a) the greater the chance of tumor regression b) the greater the risk for metastasis c) the lesser the risk of regional lymph node metastasis d) the lesser the risk of a second primary melanoma developing Instructions for Submitting Exams Fill out the postage-paid card that appears on the following page or log on to www.podiatrytoday.com and respond electronically. Within 60 days, you will be advised that you have passed or failed the exam. A score of 70 percent or above will comprise a passing grade. A certificate will be awarded to participants who successfully complete the exam. Responses will be accepted up to 12 months from the publication date.
References 1. Hyman AB, Brownstein MH. Eccrine poroma: an analysis of 45 new cases. Dermatologica 1969;138:29. 2. Penneys NS, Ackerman AB, Indgin SN, et al. Eccrine poroma. Br J Dermatol 1970;82:613. 3. Goldner R. Eccrine poromatosis. Arch Dermatol 1970;101:606. 4. Urso C, Paglierani M, Bondi R. Histologic spectrum of carcinomas with eccrine ductal differentiation: sweat gland carcinomas. Am J Dermatopathol 1993;15:435. 5. Kolde G, Macher E, Grundmann E. Metastasizing eccrine porocarcinoma: report of two cases with fatal outcome. Pathol Res Pract 1991;187:477. 6. Patrice SJ, Wiss, Mulliken JB. Pyogenic granuloma (lobular capillary hemangioma): a clinicopathologic study of 178 cases. Pediatr Dermatol 1994;8:267. 7. Strayer DS, Santa Cruz DJ. Carcinoma in situ of the skin: a review of histopathology. J Cutan Pathol 1980;7:244. 8. Wade TR, Ackerman AB. The many faces of squamous cell carcinoma. J Dermatol Surg Oncol 1978;4:291. 9. Kao GF. Carcinoma arising within Bowen’s disease. Arch Dermatol 1986;122:1124. 10. Cox NH, Eedy DJ, Morton CA. Guidelines for the management of Bowen’s disease. Br J Dermatol 1999;141:633. 11. Del Rosso JQ. Therapy for cutaneous malignancy: a review of research, development, current status and practical use of topical imiquimod. Skin & Aging 2003;11(2):44. 12. Harris MN, Gumport SL. Biopsy technique for malignant melanoma. J Dermatol Surg 1975;1:24. 13. Breslow A. Tumor thickness, level of invasion and node dissection in Stage I cutaneous melanoma. Ann Surg 1975:182:572. 14. Sober AJ, Chuang TY, Duvic M, et al. Guidelines of care for primary cutaneous melanoma. J Am Acad Dermatol 2001;45:579. 15. Nestle F, Kerl H. Melanoma. In: Bologna JL, Jorizzo JL, Rappini RP (Eds), Dermatology, First Edition, Mosby, London, 2003, pp 1789-1815.