Spotting the Zebras: Rare skin cancers

When I was a first-year medical student, one of our professors asked us during the introductory lectures, “If you see hoofprints on the ground, would you think these were left by horses or zebras?” In terms of clinical reasoning, he further explained that we should always think of more common conditions first a.k.a. the “horses” as these would be more likely based on probability. Nevertheless, there are times that we also need to think and recognise the “zebras”.

Most clinicians are familiar with common skin cancers such as basal cell carcinoma, squamous cell carcinoma and melanoma. However, we also need to be aware of rare skin cancers that may present in our practice. In this article, we will look at these “zebras” and their characteristics.

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1. Atypical fibroxanthoma (AFX)

AFX is a rapidly growing, asymptomatic, solitary dome-shaped nodule (less than 2 cm) on sun-damaged skin such as the ears, cheeks, nose, scalp and hands. It often affects elderly males, particularly those with a history of organ transplantation or certain genetic conditions (xeroderma pigmentosum).

In terms of histopathology, AFX is a poorly circumscribed tumour with a mix of spindle cells, epithelioid and multinucleated giant cells.

AFX often has local invasion beyond obviously involved skin. Recurrence rates can be quite high (up to 10% over 5 years) but has less risk of metastasis. Close follow-up is required up to 2 years after the tumour is removed. Treatment is generally with surgery, whether with Mohs micrographic surgery or wide local excision with 2-cm margins.

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2. Sebaceous carcinoma

Sebaceous carcinoma usually presents as a painless, slow-growing nodule. There are 2 types: ocular (orbit, conjunctiva, eyelid) and extraocular (head and neck e.g. face, lip, ears). It affects elderly patients, especially in males. The ocular type tends to affect more females. Risk factors include ultraviolet radiation, increasing age, genetic susceptibility (Muir-Torre syndrome) and immunosuppression.

For histopathology, there are poorly differentiated basaloid cells in sheets with infiltrative growth pattern. For the ocular type, there can be epidermal involvement with pagetoid spread (which may require conjunctival map biopsies). Factor XIIIa is positive.

Survival rates are 92% over 5 years and 79% over 10 years. Metastasis is not common but can occur in the liver and lung. The doctor might also check for lymph node enlargement. Patients also need to be assessed for a personal or family history of genitourinary or gastrointestinal cancers. In terms of treatment, wide excision with 1 cm margins to the deep fascial plane or Mohs micrographic surgery may be performed. However, extensive ocular involvement may require exenteration. In certain cases, radiotherapy, lymph node surgery, cryotherapy, chemotherapy or pembrolizumab may be considered.

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3. Dermatofibrosarcoma protuberans (DFSP)

DFSP is the most common cutaneous sarcoma which mostly affects middle-aged adults. It can also occur in children or infants. DFSP can be caused by a reciprocal translocation t(17;22)(q22:13) or a supernumerary ring chromosome composed of hybrid material derived from t(17;22). The t(17;22) translocation fuses PDGFB gene on chromosome 22 with strongly expressed collagen 1 alpha 1 (COL1A1) gene on chromosome 17. DFSP can also arise in scars.

DFSP is usually a slow-growing and asymptomatic tumour on the trunk, proximal limbs, and less commonly on the head and neck. It usually presents as a firm, indurated, skin-coloured plaque with red-brown exophytic nodules but other variants include the atrophic type, pigmented variant (Bednar tumour) or giant cell fibroblastoma (juvenile variant). There is dermal proliferation of spindle cells with a “honeycomb” pattern and fibrosarcomatous dedifferentiation can occur. CD34, vimentin and P75 are positive. There can be scattered Factor XIIIa positive cells.

DFSP is a low-grade malignancy which infiltrates diffusely through the dermis and into subcutaneous fat. It seldom metastasises to the lung or the lymph nodes. Up to half the tumours recur locally after simple excision and 5% can transform to conventional fibrosarcoma.

Treatment options include slow Mohs surgery, standard excision with 1-3 cm margins, adjuvant radiotherapy, imatinib or nilotinib.

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4. Microcystic adnexal carcinoma (MAC)

MAC can affect adult patients of both sexes over a wide age range. There is a firm, ill-defined, smooth, indurated plaque, nodule or cystic lesion which is skin-coloured or yellow with telangiectasia and an average size of 2 cm. It usually affects the central face especially around the eyes and the mouth.

Factors associated with MAC include radiation, ultraviolet exposure and follicular differentiation. Histopathology shows infiltrative growth pattern of strands, cords or cysts of tumour cells in sclerotic stroma with perineural invasion. There is often zonation with keratocysts in the superficial dermis, strands and cords of tumour cells in the mid dermis and duct-like structures in the deep dermis and subcutis. EMA, CEA, CD15 and CK7 are positive.

MAC is usually slow-growing and locally aggressive. Metastasis is rare. Treatment options include surgical excision, Mohs micrographic surgery, radiation therapy and chemotherapy.

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5. Porocarcinoma

Porocarcinoma is a nodular or verrucous growth on the lower limbs, trunk and head mostly affecting older adult patients. They can present with recent ulceration or rapid growth from an existing lesion such as a benign poroma. There are malignant basaloid epithelial cells with variable ductal formation. CK19 is positive. In terms of prognosis, 20% can recur, 20% have regional lymph node metastases and 10% can develop distant metastases. Treatment is with surgical excision, whether with conventional excision or Mohs micrographic surgery.

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6. Cutaneous angiosarcoma

Cutaneous angiosarcoma is the most dangerous entity among these rarer skin cancers. It is a highly malignant vascular tumour in adult patients. More than half arise on the head and neck. There are 3 types:

(i) Primary angiosarcoma (elderly patients on the head, neck or face)

(ii) Angiosarcoma in areas of chronic lymphoedema (e.g. Stewart-Treves syndrome arising on the upper limb after lymph node dissection for breast cancer)

(iii) Postirradiation angiosarcoma

Primary angiosarcoma initially appears as a singular or multifocal “bruise”-like patches on the face, scalp or neck. It then progresses to become violaceous, ill-defined spongy nodular tumours which bleed easily. Horizontal spread can occur to involve large areas.

For the chronic lymphoedema or postirradiation types, patients have infiltrating haemorrhagic plaques or violaceous nodules.

In terms of histopathology, well-differentiated angiosarcoma presents with irregular vascular channels lined by atypical endothelial cells in the dermis while poorly differentiated tumours have increased cellularity, nuclear atypia and mitoses. CD31 and CD34 are positive.

Prognosis is poor with 15% survival over 5 years. Small tumours can be excised with wide margins but larger tumours require radiotherapy or chemotherapy.

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7. Cutaneous leiomyosarcoma

Cutaneous leiomyosarcoma presents as solitary, deep-seated, firm nodules with occasional ulceration. It arises on hair-bearing areas on the lower limbs (more than the scalp or trunk). There is a male predominance, mostly in the 5th to 7th decades. There are two types:

(i) Dermal (fixed to the epidermis, size > 3 cm)

(ii) Subcutaneous (rapidly develop to form larger, well-circumscribed tumour nodules)

Histopathology shows intersecting fascicles of atypical spindle cells with smooth muscle differentiation.

Cutaneous leiomyosarcoma can be cured with timely wide surgical excision, either wide surgical excision with 3 cm margins with careful histologic examination of surgical margins or Mohs micrographic surgery. Metastasis can occur in up to 30-40% of those with subcutaneous involvement and usually spreads to the lung and regional lymph nodes. With Mohs surgery, there can be a 14% recurrence rate.

https://drzhenli.com/2024/08/24/spotting-the-zebras-rare-skin-cancers/