Dermpath quiz.

A 62-year-old male patient presented with severe dyspnea and multiple nodules on the skin of the scalp, hands, and back. The patient had a long history of heavy smoking. His past medical history was significant for advanced squamous cell carcinoma (SCC) of the lung and he was undergoing radiation therapy. A scalp nodule was excised and submitted for histopathological diagnosis.

Dermatopathological examination showed sheets of highly atypical basaloid cells in the epidermis and dermis [Figures 1 and 2].

Figure 1

(a) Sheets of carcinoma cells in the dermis with foci of epidermotropic involvement, hematoxylin eosin, magnification ×100. (b) Infiltrative pattern of carcinoma cells in the dermis, hematoxylin eosin, magnification ×100

Figure 2

(a and b): Epidermotropic foci of highly abnormal carcinoma cells, hematoxylin eosin, magnification ×200

In some areas abnormal cells infiltrated the epidermis [Figure 2a and b].

Immunostains with p63 and pan-cytokeratin were diffusely positive, a pattern that has been associated with primary cutaneous malignancies [Figure 3a and b].

Figure 3

(a) Diffuse positivity of carcinoma with pan-CK immunostain, magnification ×200. (b) Diffuse positivity of carcinoma with p63 immunostain, magnification ×200

The tumor most likely represents:

Primary adnexal carcinoma

Bowen's disease with invasive carcinoma

Epidermotropic metastasis

Keratoacanthoma

Primary cutaneous adenosquamous carcinoma

DISCUSSION

Areas of necrosis were present within the tumor, and served as an important clue to the diagnosis of epidermotropic metastasis. Metastases to the skin are relatively uncommon with a reported incidence of 10% among all cancer patients.[1] Epidermotropic metastases represent a group of malignancies with epidermal involvement that may mimic primary cutaneous neoplasms. The most frequent tumors which produce epidermotropic metastases include breast, cervical, and visceral SCC. We describe a case of epidermotropic metastasis of SCC of the lung, mimicking a primary cutaneous neoplasm histologically.

The first case of epidermotropic metastasis was reported by Mehregan and Pinkus in a case of breast carcinoma with epidermal involvement by neoplastic cells.[2] Incidence of epidermotropic metastasis is unknown because the literature is limited to case reports and small case series. Winzer and Kutzner reported that among 180,000 biopsy samples, they diagnosed 9 cases of epidermotropic metastases (among them metastases from the colon - 2, rectum - 2, breast - 2, uterus - 1, vulva - 1 and skin – 1). The authors, though, do not report during what time frame all the specimens were collected.

Epidermotropic metastases are known to arise from SCC from distant skin sites,[3] melanoma, porocarcinoma,[4] and Merkel cell carcinoma.[5] Metastases with epidermotropism from the internal organs are very rare and appear as occasional case reports involving adenocarcinoma of the rectum and lung,[236] breast,[7] urethra,[8] vulva,[9] cervix,[45] larynx,[7] prostatic carcinoma,[10] and bladder.[11] Clinically, epidermotropic metastases have no specific features and usually present as nodules or plaques. The clinical presentation may resemble Paget's disease, Bowen's disease, or herpes zoster infection, creating potential for confusion with a primary cutaneous neoplasm.[1213] Histopathologically epidermotropic metastases show scattered cells in the epidermis or collections of malignant cells in the epidermis similar to the Borst-Jadassohn phenomenon.[346] Rare cases of epidermotropic metastases with malignant cells affecting full thickness of the epidermis, mimicking Bowen's disease, have been reported previously.[514]

In the report we describe an epidermotropic metastasis of SCC of the lung mimicking Bowen's disease with invasive carcinoma. Lung cancers rarely metastasize to skin, and among those that do, there is a higher frequency of adenocarcinomas and large cell carcinomas.[15] The incidence of metastasis of SCC of the lung does not exceed 1–2% among lung cancer metastases.[16] Several cases of SCC of the lung metastases to the skin have been reported in the literature,[1718] but none of them demonstrated epidermotropism. Studies have shown that SCC of the lung typically has an immunohistochemical profile that is TTF-1-negative and p63/CK-positive that could be misinterpreted as representing a primary cutaneous malignancy.

Epidermotropic metastases should be differentiated from primary cancers, as management and prognosis differ greatly. Cases that resemble Bowen's disease can be challenging as invasive carcinoma in the setting of Bowen's disease is frequently anaplastic with an aggressive infiltrative growth pattern.[19-22] Clinical correlation plays a definitive role in the final diagnosis. In our patient, a histological diagnosis of metastatic disease was suspected based on the predominantly dermal location of the tumor, necrosis and only focal epidermal involvement. The pathology requisition form did not indicate concern for metastatic disease, but this suspicion was confirmed by additional clinical data obtained from the physician.

Metastasis of SCC of the lung to the skin has a grave prognosis with survival rates of about 6 months; therefore, prompt diagnosis is critical to allow proper care and counseling.