Eccrine porocarcinoma, tricholemmal carcinoma and multiple squamous cell carcinomas in a single patient

ARTICLE

Multiple skin carcinomas are not uncommon and can be observed in patients with genetic defects, such as Gorlin syndrome or xeroderma pigmentosum, in patients who were exposed to arsenic, photochemotherapy, hydrocarbons or X ray therapy, in immunosuppressed patients [1] or for unknown reasons. We report the case of a 75-year old woman who successively developed a porocarcinoma, multiple squamous cell carcinomas and a tricholemmal carcinoma within a one-year period.

Case report

A 75-year old woman was first seen for a tumor located on her left leg. She had had a lesion for more than 4 months, that was first treated by various topical treatments, including neomycin. She developed an intense contact dermatitis of the left leg centered by an ulcerated tumor of 2.5 cm diameter. Clinical examination revealed multiple other tumors: a bluish nodule that seemed cystic and a keratotic tumor of the right leg, two keratotic papules of 1 cm diameter on her arm and thigh, and multiple actinic keratoses on her forehead.

Histopathological examination of the three small tumors showed typical Bowen's disease in two samples (thigh and arm) and a well differentiated squamous cell carcinoma (right leg). The lesion of the right leg was an intradermal epithelial tumor made of large pseudo-cystic structures (Fig. 1). The cavities were bordered by aggregations of round cells that showed crowded and atypical large nuclei with numerous mitotic figures (Fig. 2). Both basaloid and squamous cells were identified as well as dyskeratotic cells which allowed the diagnosis of pseudo-cystic squamous cell carcinoma. Staining for carninoembryonic antigen was negative.

The ulcerated tumor of the left leg invaded the whole dermis and hypodermis, and was made of nests and strands of small and regular basophilic poral cells. The tumor was sharply demarcated from the normal epidermis at each side (Fig. 3). Numerous atypical nuclei and mitoses were present. In the deep part of the dermis small nests of cells detached from the central tumor and were surrounded by clefts that made a sharp demarcation between the tumoral cells and the stroma. Immunohistochemical staining for carcinoembryonic antigen proved positive in the malignant cells, showing the presence of some lumina inside the deep nests of cells. All these features were those of trabecular eccrine porocarcinoma, without remnants of previous benign eccrine poroma. Because the tumor was incompletely removed, a surgical excision down to the underlying fascia was necessary. The same masses of malignant poral cells were observed in the dermis and sucutis. Six months after surgery, ulcerated nodules appeared in the center of the cicatricial area of the leg (Fig. 4). Histopathological examination revealed a recurrence of the eccrine porocarcinoma with intra-lymphatic nests of basophilic cells in the deep part of dermis on both sides of the tumor. A second large and deep excision was then performed. There were no lymph node enlargement or visceral metastases. This tumor did not recur during a 3 year-follow-up. Nevertheless, one year after the first surgery, the patient developed a large exophytic and ulcerated tumor of the forehead (Fig. 5) which showed a very rapid growth over 3 months, reaching 2.5 cm in diameter.

Histopathological examination showed large masses of clear atypical cells (Fig. 6) with a trabecular growth pattern and invasion of the deep dermis. Typical features of outer root sheath differentiation were found, especially palisading of clear cells with subnuclear vacuolization in the periphery of the tumor lobules. Areas of tricholemmal keratinization were noted in some of the tumoral strands. The nuclei were very large and the cell cytoplasm was strongly PAS-positive. Multiple mitotic figures were observed, most of them being atypical. All these features were typical of tricholemmal carcinoma. During a 2-year follow-up after excision, there was no recurrence of this facial tumor. This patient was carefully questioned about her past medical history. She had neither past visceral neoplasms nor lymphoma or leukaemia. She had never received immunosuppressive treatment, X-ray therapy or exposure to arsenic. There was no familial history of cancer. This patient was a native French woman and had not been overexposed to solar irradiation for occupational reasons, although she presented with numerous actinic keratoses.

Discussion

To our knowledge, this is the first report of a single patient presenting in a one-year period of time multiple carcinomas of unrelated histogenesis. Both eccrine porocarcinoma [2, 3] and tricholemmal carcinoma [4, 5] are very unusual neoplasms. Eccrine porocarcinoma of the trabecular type [3] is often very invasive and recurrences are frequent. Despite local recurrence, our patient did not develop metastatic disease, which seems to be more frequent in the epidermotropic type of this neoplasm [3, 6]. The main histopathological features that are important for the diagnosis were the trabecular pattern, intracytoplasmic ducts, poral basophilic cells with atypical nuclei and abnormal mitoses and clefts around the tumoral cells.

The tumor of the forehead was also very characteristic of a tricholemmal carcinoma [4, 5]. This neoplasm occurs in elderly patients, shows a rapid course and usually affects the face. In our patient, tumoral cells showed the very typical features of outer root sheath cells. Tricholemmal carcinoma has certainly malignant histological features, but recurrences or metastases are uncommon [4, 5].

The diagnosis of cystic squamous cell carcinoma can be difficult. As stated by Ackerman et al. [7], differentiating proliferating cystic follicular neoplasm [8, 9] and squamous cell carcinoma is "a vexing problem". The tumor illustrated in Figures 1 and 2 is very similar to the squamous cell carcinoma demonstrated by Ackerman et al. on p. 566 of their book [7]. It is likely that this neoplasm represents a rare variant of pseudo-cystic and poorly differentiated squamous cell carcinoma [7]. This tumor was obviously malignant by cytological criteria. Eosinophilic cells and keratinization were both consistent with an unusual form of squamous cell carcinoma. Because this tumor was not connected with the overlying epidermis, other carcinomas could be discussed. The diagnosis of sweat gland carcinoma is unlikely, because of the presence of numerous eosinophilic cells with features of keratinization, absence of ductal structure, and negative staining for carcinoembryonic antigen. A pilar origin cannot be totally ruled out, but we could not find clear cut evidence in favor of the hypothesis of pilar carcinoma.

The occurrence of multiple carcinomas in a single patient could be fortuitous, but five unrelated malignant cutaneous tumors were removed in a one-year period of time in this case. Multiple Bowen's diseases are not uncommon, but we did not find any similar case associated with adnexal and squamous cell carcinomas in the literature. Nevertheless, we could not detect a predisposing factor in this patient who remained in good general health during the follow-up. A genetic disease is unlikely, since the patient did not develop skin neoplasms before the age of 75 years. Multiple adnexal tumors are described in the Muir and Torre syndrome, but they are mainly of sebaceous origin. In this patient, no other internal malignancies could be found in association with the skin findings, and she is still alive more than 4 years after the first tumor occurred. External carcinogenic factors are not known to induce adnexal neoplasms and none of those factors previously described could be evidenced in our patient. The occurrence of tricholemmal carcinoma in a 39-year-old organ transplant-recipient has been reported [5]. Our patient had a normal lymphocyte count and had never been treated by immuno- suppressive drugs. One of the cases of tricholemmal carcinomas described by Swanson et al. was associated with past multiple basal cell carcinomas [10]. Since the majority of tricholemma carcinomas are located on sun-exposed areas, it can be hypothesized that actinic damage could play a role in this type of tumor. Eccrine porocarcinoma developed in a 12-year-old child with xeroderma pigmentosum and could have therefore been enhanced by abnormal DNA repair mechanism [3]. It is likely that carcinogenetic factors involved in the development of squamous ­ or basal ­ cell carcinomas could also play a role in some cases of adnexal carcinomas. Apart from sun exposure, no specific factor could be evidenced in our patient.

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