Selected Sweat Gland Carcinomas

Summary: Porocarcinoma

•A rare sweat gland carcinoma that usually arises de novo, but can develop from malignant transformation of benign poroma.

•Potential for epidermotropic metastases.

•Patients developing metastatic disease have a high mortality.

•Histological factors that may predict behavior include mitoses per high power field greater than 14, lymphovascular invasion, and tumor depth greater than 7 mm.

H.A. Oriba (*)

Department of Mohs Surgery, The Skin Cancer Center, Sun City Center, FL, USA

e-mail: horiba@pol.net

S.N. Snow

Department of Dermatology,

University of Wisconsin School of Medicine & Public Health,

Madison, WI, USA

25.1Porocarcinoma

Porocarcinoma (PC) is an uncommon carcinoma originally described in 1963 as epidermotropic eccrine carcinoma [1]. Other terms used to describe this lesion include malignant eccrine poroma, malignant porosyringoma, malignant hidroacanthoma simplex, eccrine adenocarcinoma, and poroepithelioma. This tumor is of eccrine origin, arising from the acrosyringeum, which is the intraepidermal portion of the eccrine duct.

Fig. 25.1 Porocarcinoma. A 54-year-old man with a hyperpigmented, non-healing tumor of the right ankle. The central ulceration was the result of the biopsy (Courtesy of Thomas Rozum M.D., Berlin)

PC usually presents as a verrucous nodule, or plaque, mostly on acral areas of the lower extremities [2–6] (see Fig. 25.1). They appear moist and tend to bleed with minor trauma. Other reported sites included head and neck, trunk, vulva, breast, and upper extremity. In contrast, benign eccrine poromas occur mostly on palms and soles. Clinical lesion size is variable, ranging from less than 1 to 10 cm. Most patients are older than 50 years of age, but PC is known to present in all age groups. Interestingly, PC can arise in preexisting poroma that has clinically become symptomatic, suggesting that PC arise via malignant transformation which may be manifested by bleeding, ulceration, increase in size, or pain. Spontaneous cases are also known to exist as well [6, 7]. PC has also arisen in organoid nevus [8], and seborrheic keratosis [9–11]. There appears to be no sexual or ethnic predisposition.

Clinically, PC initially is a slow-growing lesion, and then enters a proliferative, vertical growth phase with propensity to metastasize to regional lymph nodes. Several large review series report a frequency of about 20% [5, 6]. However, other series have reported less-frequent lymph node metastasis [2, 3, 12]. Visceral metastases can occur in about 10–12% of the cases [5, 6], and invariably lead to fatal outcome [5, 13–16]. Parameters for sentinel lymph node biopsy of PC have not been defined; nevertheless, it is clear that dissemination to lymph node or visceral organs portends high morbidity and tends to lead to a fatal outcome.

The histopathology of PC can consist solely of an intraepidermal component or with dermal invasion. The intraepidermal tumor cells are small basaloid cells that are arranged in nests and islands that abruptly contrast with eosinophilic keratinocytes. Single pagetoid spread is not seen. Dermal invasion occurs with broad anastomosing columns of tumor cells to varying levels of the dermis (see Fig. 25.2). The cells appear clear because they contain varying amounts of glycogen, hence PAS positive, diastase labile. Cytologic atypia is manifested by hyperchromasia, atypical mitotic figures. Ductal structure can be present, helpful in the histological diagnosis, and can be highlighted with immunohistochemical staining with carcinoembryonic antigen and epithelial membrane antigen [17]. Other histological features that may be present include foci of squamous differentiation [18, 19] (see Fig. 25.3), clear cell areas [18], and melanin pigment [20]. Perineural involvement has been reported [6]. One study found features associated with aggressive clinical behavior and poor prognosis that included mitoses per high power field greater than 14, lymphovascular invasion, and tumor depth greater than 7 mm [5]. Tumors with an infiltrative or pushing border had increased risk of local recurrence [5].

An important distinction is warranted when PC presents as an in situ form [21]. This histological presentation can represent in situ PC, epidermotropic porocarcinoma, or a cutaneous metastasis of PC. Epidermotropic porocarcinoma is a pattern seen adjacent to PC and metastatic PC. Cutaneous metastasis of PC demonstrates small epidermotropic deposits of PC, and clinically appears as multiple cutaneous deposits in a lymphangitic pattern. Separating these similar histological presentations can be difficult and impossible without clinical correlation. The epidermotropic porocarcinoma presentation may represent a field effect in which the neoplasia is multifocal. Epidermotropism may not be an independent risk for aggressive clinical behavior [6]. The histological differential diagnosis of epidermotropic PC includes Bowen’s disease, extramammary Paget disease, and melanoma in situ. Special stains are needed to delineate these entities.

Surgical excision is the main therapeutic approach. The role of prophylactic lymphadenectomy is controversial. Sentinel lymph node biopsy has been used to stage PC [22], and should be considered for histologically aggressive lesions. PC does not respond primarily to radiotherapy [23] or chemotherapy. Chemotherapy may play a role in treating metastatic

eccrine porocarcinoma [24, 25]. Since there is limited experience with Mohs micrographic surgical treatment of PC, its role in treatment remains unresolved. A total of 15 cases have been reported in English literature with favorable outcomes [11, 26–30] (see Table 25.1). No signs of recurrence were noted with a mean follow-up period of 23 months. Due to potential metastatic spread of PC, early intervention with Mohs micrographic surgery maybe a suitable approach. Other indications could include treating in situ lesion, or PC in non-proliferative growth phase where metastasis have not occurred. Care must be taken when evaluating Mohs layer since pagetoid extension of PC cells may be in a noncontiguous, multifocal pattern. Extra Mohs layer may be indicated after initial clear layer is obtained. Toluidine blue stain may aid in some cases; however glycogen-containing cell in PC can be variable. Further studies are needed to validate this therapeutic approach.

Summary: Hidradenocarcinoma

•Is a highly aggressive neoplasm, which may metastasize widely, and is fatal.

•Can occur in a wide range of age group, and has been seen children.

•Most cases arise de novo.

•Tumor can have foci of bland-appearing histology; hence all areas of tumor need to be extirpated.

25.2Hidradenocarcinoma

Hidradenocarcinomas (HC) are an extremely rare form of sweat gland carcinomas that have an aggressive, potentially fatal course. It was originally described in 1949 [31], but the literature is strewn with synonyms

Fig. 25.4 Hidradenocarcinoma. A 45-year-old man with a biopsy-proven HAC of the scalp. When the patient presented for Mohs surgery, another subcutaneous tumor (purple circle) developed on the right postauricular scalp. Biopsy confirmed a metastatic lymph node metastasis [143]

such as malignant acrospiroma, malignant hidradenoma, clear cell eccrine carcinoma, malignant clear cell myopepithelioma, and clear cell papillary carcinoma. It may represent both apocrine and eccrine derivation [32].

HC can present in patients of any age, though favor older patients, but cases have been reported in children [33] and at birth [34]. They can present as a solitary flesh-colored nodule, erythematous or ulcerated nodule of variable size [35] (see Fig. 25.4). Most occur on the head and neck region, and less commonly on extremities or trunk [34, 36]. Other sites of presentation include hands, feet, eyelids, axilla, and vulva [3]. The natural history of this lesion is varied [34, 36]. Rarely, some lesions remain localized; however, most have an aggressive course, metastasizing to lymph nodes, bones, and other visceral organs. Malignant transformation has been reported [3, 37–39].

The histopathology of HC is distinguished from its benign counterpart by displaying features of infiltrative pattern, loss of circumscription, and asymmetry at low power magnification. Solid and cystic spaces are present; however, the cystic spaces and ducts may be irregularly shaped. Cytologically, the tumor cells are composed of round and polygonal cells with biphasic cytoplasmic content. One type of cells has a clear cytoplasm with eccentric nuclei, and the second cell type has eosinophilic cytoplasm with a round or oval vesicular nuclei (see Fig. 25.5).

As in the benign counterpart, the biphasic cellular population ratio can vary. The clear cells contain glycogen, some PAS-positive, diastase-resistant material as well. Lipid is not present. Mitotic figures are usually present; however, lack of them does not signify benignity. Both benign and malignant counterparts of hidradenoma can have mitoses in varying ratios. Cellular pleomorphism may be minimal or absent. Melanocytes can occasionally be found as well. Therefore, with diminished clear cell changes, bland appearance, a specimen can pose a challenging interpretation. At times, distinction from benign hidradenoma cannot be made. The histological differential diagnosis can include a benign hidradenoma, malignant eccrine spiradenoma, and malignant chondroid syringoma. Adequate tissue sampling is critical aspect to making the correct diagnosis. Immunohistochemical studies are not helpful in differentiating benign from malignant hidradenoma.

Surgery is treatment of choice. All patients should be staged prior to treatment. The literature advocates wide excision with consideration of prophylactic lymph node dissection [33, 40, 41]. Margins have not been defined. Sentinel lymph node biopsy could aid in staging due to HC’s potential to metastasize [42] There are reports that postoperative radiation may be helpful [43–45], and chemotherapy may play an adjunctive role [46, 47]. Adjunctive hormonal therapy may also be helpful, particularly targeting estrogen receptors [42, 48], and Her-2/neu protein [49].

The Mohs micrographic surgical experience is limited for this carcinoma. Seven cases have been treated to date with Mohs micrographic surgery [29, 50–53]. A review of the limited cases suggests adequate local control, but there was limited follow-up (see Table 25.2). No recurrences were observed with a mean follow-up time of 26 months. Patients should have a thorough physical examination and staging with imaging studies prior to treatment. Sentinel lymph node biopsy should also be considered. One should consider obtaining tumor marker studies such as estrogen and Her-2/neu.

If Mohs micrographic surgery is contemplated, a number of potential issues come to mind. First, frozen section artifacts may come into play. Clear cell changes and ducts may be difficult to visualize. Since this tumor can extend to the subcutis, one should consider taking a deeper layer, possibly into adipose. Complete removal of the tumor would

Table 25.2 Mohs surgery experience with hidradenocarcinoma

NA data not available, – none aRecurrent hidradenoma bMetastatic on presentation

cReceived postoperative radiotherapy

include bland-appearing areas, since HC can have bland areas and potential for malignant transformation if left behind. Perhaps, the last layer should include permanent H&E sections. The role of

immunohistochemistry in Mohs sections of HC has not been studied. At present it plays a limited role, but in the future, could help in evaluating Mohs sections.