Proliferating trichilemmal tumor (PTT) is a benign tumor originating from the outer root sheath of a hair follicle, that are usually found on the scalps of women in their seventies and eighties. Although considered biologically benign, PTT may be locally aggressive [1]. It was first described by Wilson-Jones in 1966 as “proliferating epidermoid cyst” and since then, a number of terms have been used to describe this lesion [2], such as subepidermal acanthoma, invasive hair matrix tumor, invasive pilomatrixoma, trichochlamydocarcinoma, hydatidiform keratinous cyst, giant hair matrix tumor, trichochlamydoacanthoma, and pillar cyst [3].

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Figure 1. Ttrichilemmal cyst with an area of malignant proliferating trichilemmal tumor (Microphoto).

Tumors with an invasive growth pattern or cytologic atypia have an unpredictable course and may be locally aggressive or metastasize. Thus, it has been suggested that even the classical PTT should be considered as carcinoma [4]. Malignant transformation in case of PTT is very rare and unusual finding and less than 100 well-documented cases of malignant PPT have been reported so far in the literature. It is usually confused with squamous cell carcinoma both sharing many common features [5]. We report here a case of malignant PPT in a man, who presented to us with a swelling scalp lesion; histological findings with immunohistochemistry markers are presented in this observation.

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Figure 2. Peripheral palisading epitheilum with large keratinocytes and abrupt trichelemmal keratinization (HEx20).

A 53-year-old man, with no medical history, presented with a gradually enlarging lesion during last year, on the scalp that was otherwise asymptomatic. The lesion had evidently been growing in the last 4 months. He denied trauma or insect bite at this location. On physical examination a localized, non-painful skin colored nodule with a smooth surface, soft consistency, and was not fixed to the underlying bone, measuring 1.5 x 3.5 cm was observed. There were no palpable adenomegalies in the neck. Systemic examination was normal. An excisional biopsy was performed, removing the entire lesion followed by curettage and the tissue was sent for histopathological examination.

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Figure 3. Proliferating nests of squamoid cells with wide eosinophilic cytoplasm and features of anaplasia (Hex10).

Grossly, the specimen measured 3.5×1.5×1.0 cm. On cut surface, it was a cystic mass filled with yellow-tan fluid presenting focally as a gray-white solid tumor measuring 1×1×0.5 cm. Microscopic examination of the excised specimen revealed a cystic lesion, encapsulated and well circumscribed (Figure 1), showing area of ordinary trichilemmal cyst lined by peripheral palisading of small basaloid cells, differentiating towards large keratinocytes with ample eosinophilic cytoplasm and abrupt trichelemmal keratinization (Figure 2). We noticed focally, proliferating nests of squamoid cells with wide eosinophilic cytoplasm and features of anaplasia (increase in the nucleo-cytoplasmic ratio, nuclear hyperchromasia or nuclear polymorphism and mitotic figures) throughout separated by fibrous stroma. There were extensive dyskeratosis-forming masses of cells with areas of necrosis (Figure 3,4).

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Figure 4. Proliferation showing dyskeratosis-forming masses and well demarcation (Hex20).

The excision was large with no residual tumor. Immunohistochemical staining with ki67 observed in 40% tumor cells (Figure 5). The resected surgical margins of the mass were free of tumor. Based on the histopathological findings, the diagnosis of well-differentiated malignant PTT was made.

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Figure 5. Immunohistochemical staining with ki67 (HEx10).

Cutaneous tumors derived from the outer root sheath of hair follicles, which show trichilemmal keratinization, including trichilemmal cysts, proliferating trichilemmal cysts and malignant proliferating trichilemmal tumor. They are infrequent, comprising only 0.1% of skin biopsies with the malignant counterpart being even rarer [6].

Most patients are women (84%) who range in age from 27 to 83 years [10] and more than 90% of the lesions are localized on the scalp; face, nose, trunk, back, wrist, chest, abdomen, buttocks, elbow, pubis and vulva can also be affected [7]. This is an exceptionnal case involving a 53-year-old male with rapidly enlarging mass on his scalp. Etiopathogenesis remains unknown, but in most cases it appears to develop within the wall of a pre-existenting pilar cyst as a complication of trauma and/or inflammation. It has also been reported to develop in nevus sebaceous and human papillomavirus has also been implicated [8]. PTT can occur de novo, as in our report. Malignant proliferating trichilemmal tumor (MPTT) is the rarest of trichilemmal tumors. Malignant PTT (MPTT) is an uncommon cutaneous neoplasm that has been the subject of controversy in the dermatology literature [9]. The term MPTT was entered in literature by Saida et al [10], because of a PTT that showed infiltrative growth, marked cytological atypia, high mitotic activity including atypical forms, and lymph node metastases [9].

Malignant transformation can be manifested by sudden rapid growth, ulceration, itchy, red swelling nodule [9]. Histologically, malignant PTTs show severe nuclear atypia, marked cellular pleomorphism with atypical mitoses, dyskeratotic cells, infiltrating margins and metastasis [11]. Anaplasia, if found, is the hallmark of malignancy, but cellular atypia and anaplasia may be surprisingly absent in some cases [12]. Nevertheless, it is accepted that cytologic atypia may be present in PTT that ultimately have a benign behaviour. This issue remains controversial since tumors with little or no cytologic atypia may be aggressive, showing that their histologic appearance does not necessarily correlate with their biological behavior [4]. Therefore, as proposed by some authors, it is advisable to consider PTTs with those features as being at high risk of malignant transformation. It has been proposed that a nonscalp location, recent rapid growth, size larger than 5 cm, infiltrative growth and important cytologic atypia with mitotic activity should be regarded as malignancy [6].

The real incidence of a malignant proliferating trichilemmal cyst is unknown, due to its rarity and also to inconsistencies in nomenclature and misclassification as squamous cell carcinoma [13].

Unfortunately, distinctive histological or immunohistochemical markers of malignancy do not exist [11]. Proliferation markers like Ki67 and p53 can assist in the differential diagnosis. Recently, a clinicopathological study of 76 cases divided PPT into three groups based on the degree of stromal invasion and the level of cytological atypia – benign, low- and high-grade malignancy. According to the classification suggested by Ye et al, Ki 67 is only focally positive in <5% of the basal cells in trichilemmal cysts and benign PPT as compared with 30 to 40% in malignant PPT [14] [15] [16]. Our case showed Ki67 positivity in 60% of the cells . The differential diagnosis of MPTT includes squamous cell carcinoma and trichilemmal carcinoma. Features favoring the diagnosis of MPTT including the scalp location, the presence of trichilemmal type keratinization, and the lack of a precursor epidermal lesion such an actinic keratosis. Besides, there is always connection to the epidermis [6].

Due to its rarity there are no guidelines available for the management of these tumors. The therapeutic approach in malignant proliferating trichilemmal tumor consists of wide local excision with a 1cm margin of normal tissue and long-term follow-up. The patient should be followed closely after surgery. The efficacy of alternative treatments for malignant cases cannot be safely evaluated in view of the very small number of published cases [9]. Chemotherapy and radiotherapy have been used by some authors in addition to local excision to prevent recurrence [14]. Malignant proliferating trichilemmal tumor has greater malignant potential than histologically similar cutaneous squamous cell carcinoma [14], particularly the tumors greater than 5cm or with spindle cell components [3].

In our case, the excision was complete, and clinical exam and CT revealed no distant metastasis. The patient has been followed by dermatologists.

In summary, this is a case of a rare man’s tumor. The tumor poses a diagnostic dilemma for the pathologists with uncertain clinic behavior and prognosis. Additional studies will help to reinforce the prognostic value of ki67 immunostaining and other markers in PTCs.

Written informed consent was obtained from the patient for publication of this Case Report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.

The authors declare that they have no competing interests.

I.H was the principal author and major contributor in writing the manuscript. T.H reviewed the article and revised it critically.

All authors read and approved the final manuscript.

We are grateful to the department of Dermatology, UH Hassan II, for examining the patient, doing the excision biopsy and referring the specimen to our laboratory for histologic exam. Thanks for Dr H.T. for reviewing the manuscript, elaborating many productive ideas and being all along during the preparation of this manuscript.