Malignant cutaneous adnexal neoplasms are an uncommon group of low-grade carcinomas. Although most of these tumors have very limited ability to spread to distant sites, they are locally aggressive and must be treated with surgical excision to ensure tumor-free margins. Malignant cutaneous adnexal neoplasms have distinctive histopathologic characteristics, but their clinical characteristics are largely nonspecific. The type of differentiation present in each tumor is recognizable through histopathologic characteristics that resemble certain findings present in the corresponding normal adnexal structures. Generally speaking, as these tumors are malignant, they show few signs of differentiation. Investigation through serial cuts or immunohistochemical staining is therefore necessary to establish the type of differentiation in a given adnexal tumour. Many malignant cutaneous adnexal carcinomas display only ductal differentiation, and as eccrine and apocrine ducts are currently indistinguishable both immunohistochemically and ultrastructurally, all that can be clearly established in such cases is that the tumour is a ductal carcinoma. No further differentiation is possible. Although differentiation is minimal, however, certain histopathologic features, summarized in Table 1, can suggest malignancy. In this article, we review the malignant cutaneous adnexal neoplasms listed in Table 2.

Pilomatrix carcinoma presents as a solitary nodule on the upper body in the vast majority of cases.1 It is more common in middle-aged and elderly men. Most publications to date have described a largely nonaggressive biologic behavior, but there have been reports of metastasis to regional lymph nodes and internal organs with fatal outcomes.2

Histopathologically, pilomatrix carcinoma is seen as an asymmetric, poorly circumscribed tumor with frequent ulceration of the epidermal surface. It consists of a proliferation of immature basaloid cells, reminiscent of follicular matrical cells, that form either solid basaloid islands or cords of cells penetrating the deep dermis, subcutaneous tissue, and even the fascia and muscle (Fig. 1). The most common finding is the presence of islands of shadow cells indicating matrical differentiation.3

Figure 1.

Histopathologic characteristics of pilomatrix carcinoma. A, Panoramic view showing a lesion formed by numerous tumor islands invading the dermis. B, Islands of matricial cells containing shadow cells in the center. C, Detail of matricial and shadow cells. D, High-magnification view of neoplastic cells with matricial differentiation. (Hematoxylin-eosin, original magnification ×10 [A], ×40 [B], ×200 [C], ×400 [D]).

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Sebaceous carcinoma is classified as ocular or extraocular. The distinction is based not only on anatomic location but also on the greater metastatic potential of the ocular variant, although this has recently been questioned.10

Sebaceous carcinoma of the eyelid generally affects elderly patients and is frequently interpreted as an inflammatory lesion, resulting in a delayed diagnosis. Most cases of extraocular sebaceous carcinoma occur on the face and neck of elderly patients. Clinically, the lesion presents as a nodule or indurated plaque that may be ulcerated.

Histopathologically, sebaceous carcinoma presents as a poorly circumscribed tumor formed by islands of epithelial cells that invade the dermis or the chorion of the conjunctival mucosa in the case of eyelid involvement. Subcutaneous tissue involvement is also common (Fig. 2). Cytologic degree of sebaceous differentiation is variable. Some tumors show immature basaloid cells, while others show neoplastic cells with morphologic features of mature sebocytes, a cytoplasm containing numerous lipid vacuoles, and a retracted nucleus with spiculated borders due to the pressure exerted by the lipid vacuoles on the nuclear membrane. Detection of ducts with a similar morphology to that of sebaceous ducts, with a serrated cuticle, can aid diagnosis.11 Adipophilin is a very useful immunohistochemical marker for identifying sebaceous differentiation in formalin-fixed or even paraffin-based tumor specimens.12

Figure 2.

Histopathologic characteristics of sebaceous carcinoma. A, Panoramic view showing islands of neoplastic cells invading the full thickness of the dermis. B, Several neoplastic aggregates showing a tendency to converge. C, Detail of sebaceous differentiation in the form of sebocytes at different stages of maturation. D, Sebocytes at different stages of maturation. (Hematoxylin-eosin, original magnification ×10 [A], ×40 [B], ×200 [C], ×400 [D]).

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Most cases of syringocystadenocarcinoma papilliferum appear to arise from the malignant transformation of an existing syringocystadenoma papilliferum and almost always against the background of nevus sebaceous of Jadassohn.16 Syringocystadenocarcinoma papilliferum is more common in women and has a predilection for the scalp. Clinically, it presents as a plaque consisting of multiple confluent yellowish papules, some of which may be ulcerated or crusted.

Histopathologically, syringocystadenocarcinoma papilliferum is similar to its benign counterpart, as it is formed by large papillary structures. Unlike syringocystadenoma papilliferum, however, it appears as an asymmetric, poorly circumscribed tumor that invades the hypodermis and underlying tissues. Papillary structures penetrate cystic cavities, which are connected to the skin surface through pre-existing infundibular structures and are lined by an epithelium with clear signs of atypia and frequent mitotic figures (Fig. 3).17

Figure 3.

Histopathologic characteristics of syringocystadenocarcinoma papilliferum. A, Panoramic view showing neoplastic aggregates of varying shapes and sizes invading the dermis. B, Papillary structures connected to the epidermal surface. C, Note how these papillary structures are lined with a double layer of epithelial cells. D, Images of nuclear atypia and pleomorphism in the epithelial cells lining the papillae. (Hematoxylin-eosin, original magnification ×10 [A], ×40 [B], ×200 [C], ×400 [D]).

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Apocrine tubular carcinoma is more common in middle-aged women. It appears as a firm subcutaneous nodule sometimes fixed to the underlying tissue. It has a predilection for the axillae.

Histopathology shows multiple, closely packed ductal structures occupying the full thickness of the dermis and the subcutaneous tissue. As the lesion penetrates into the dermis, the glandular lumina and neoplastic aggregates become progressively smaller (Fig. 4). Before making a diagnosis of primary tubular carcinoma, it is necessary to rule out a cutaneous metastasis from a visceral adenocarcinoma or a tubular carcinoma in the axillary tail of the breast.

Figure 4.

Histopathologic characteristics of tubular carcinoma. A, Panoramic view showing tubular structures invading the dermis. B, Tubular structures immersed in a sclerotic stroma. C, Tubular structures of varying shapes and sizes. D, Signs of decapitation secretion in one of the tubules. (Hematoxylin-eosin, original magnification ×10 [A], ×40 [B], ×200 [C], ×400 [D]).

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Papillary carcinoma is more common in men and has a clear predilection for the fingers, where it presents as a firm, sometimes ulcerated, subcutaneous nodule.

Despite its name, papillary carcinoma is a predominantly solid tumor. The only predominant focal features are tubular structures containing papillae.25 Histopathologically, neoplastic cells appear as basaloid cells with a hyperchromatic nucleus that tend to form solid aggregates (Fig. 5).

Figure 5.

Histopathologic characteristics of papillary carcinoma. A, Panoramic view showing a tumor invading the full thickness of the dermis and extending into the subcutaneous tissue. B, Neoplastic aggregates of varying shapes and sizes. C, Traces of papillary structures in some of the neoplastic aggregates. D, Detail of the papillary structures. (Hematoxylin-eosin, original magnification ×10 [A], ×40 [B], ×200 [C], ×400 [D]).

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Hidradenocarcinoma papilliferum frequently arises in an existing hidradenoma papilliferum. Most cases to date have been described in the anogenital region of middle-aged women. The lesions present as protruding tumoral lesions or subcutaneous nodules, sometimes accompanied by an ulcer with a bloody exudate. In most cases, they are clinically interpreted as superinfected cysts.

When viewed under low-power magnification, hidradenocarcinoma papilliferum has a similar appearance to that of hidradenoma papilliferum, as it is formed by a cystic structure with papillary structures protruding into the cyst. Careful examination, however, shows an irregular architecture with invasion of adjacent tissue. The papillary structures are composed of a central core of fibrovascular tissue lined by a double layer of epithelial cells marked by nuclear pleomorphism and frequent mitotic figures.28

Apocrine hidradenocarcinoma is more common in men in their 50s. The tumor presents as an asymptomatic subcutaneous nodule with nonspecific clinical features.

Histopathologically, apocrine hidradenocarcinoma appears as a multilobulated tumor with solid islands of neoplastic cells of varying shapes and sizes that display deep, asymmetric invasion (Fig. 6). Tubular structures are evident in most tumors, and decapitation secretion at the luminal border is occasionally seen.29

Figure 6.

Histopathologic characteristics of papillary apocrine hidradenocarcinoma. A, Panoramic view of a tumor invading the full thickness of the dermis. B, Neoplastic aggregates of varying shapes and sizes. C, Note the cells with a pale cytoplasm in some of the neoplastic aggregates. D, Detail of a neoplastic aggregate with ductal differentiation. (Hematoxylin-eosin, original magnification ×10 [A], ×40 [B], ×200 [C], ×400 [D]).

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Malignant mixed tumor has no distinctive clinical characteristics and presents as a subcutaneous nodule with occasional epidermal ulceration. It sometimes invades the underlying tissues and appears fixed to the deep layers. Histopathologically, it displays an irregular architecture with a double epithelial and mesenchymal component. The epithelial component contains ducts and small tubules, while the mesenchymal component is typically myxoid (Fig. 7), although it may be chondroid or osteoid.31

Figure 7.

Histopathologic characteristics of malignant mixed tumor. A, Panoramic view showing a poorly circumscribed tumor. B, Aggregates of neoplastic epithelial cells immersed in a myxoid stroma. C, Neoplastic aggregates formed by cells with an atypical, pleomorphic nucleus. D, Signs of ductal differentiation in some of the aggregates. (Hematoxylin-eosin, original magnification ×10 [A], ×40 [B], ×200 [C], ×400 [D]).

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Malignant transformation of an existing cylindroma is more common than de novo malignant cylindroma and occurs more frequently in patients with multiple lesions. The lesions suddenly exhibit rapid growth and on occasions epidermal ulceration following years of stable disease. In many cases, the tumor will already have invaded the underlying cranial bone by the time the patient is seen.

Histopathologically, malignant cylindroma is seen as multiple islands of basaloid cells arranged in a jigsaw-like pattern (Fig. 8), similar to that seen in its benign counterpart. The benign and malignant variants can coexist in the same lesions and there may even be a gradual transition between the two. Architectural asymmetry and cellular atypia, combined with necrotic areas, are strongly diagnostic of malignant cylindroma.32

Figure 8.

Histopathologic characteristics of malignant cylindroma. A, Panoramic view showing a poorly circumscribed tumor invading the full thickness of the dermis. B, The tumor is formed by aggregates of neoplastic basaloid cells. C, Aggregates distributed in a jigsaw-like pattern. D. Detail of one of the neoplastic aggregates surrounded by a thick basement membrane. (Hematoxylin-eosin, original magnification ×10 [A], ×40 [B], ×200 [C], ×400 [D]).

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Spiradenocarcinoma typically arises in a long-standing spiradenoma that suddenly starts to grow. It is more common on the extremities, although it can affect any part of the body.

Histopathologically, spiradenocarcinoma is classified as poorly or well differentiated. Well-differentiated tumors have similar findings to spiradenoma, with epithelial aggregates of basaloid cells containing multiple ductal structures (Fig. 9). The lesions, however, are asymmetric and poorly circumscribed, and show islands of epithelial cells of greatly varying shapes and sizes, in addition to frequent necrotic areas and invasion of adjacent tissue. In the case of poorly differentiated spiradenocarcinoma, a definitive diagnosis can only be established if traces of spiradenoma are observed in the vicinity of an undifferentiated carcinoma. On occasions, this poorly differentiated tumor may contain spindle cells, leading to confusion with sarcoma.34

Figure 9.

Histopathologic characteristics of spiradenocarcinoma. A, Panoramic view showing a spiradenoma in the dermis and a spiradenocarcinoma nodule in the subcutaneous tissue. B, The nodule is formed by a sheet of neoplastic cells. C, Note the pleomorphic nuclei and frequent mitotic figures in the neoplastic cells. D. High-magnification view of neoplastic cells, several of which are in mitosis. (Hematoxylin-eosin, original magnification ×10 [A], ×40 [B], ×200 [C], ×400 [D]).

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Syringoid carcinoma is a slow-growing tumor with a predilection for the head. It presents as a subcutaneous nodule or plaque that is noticeably hard on palpation.

Histopathologically, it is characterized by multiple ductal structures and small cysts that occupy the full thickness of the dermis and frequently invade the subcutaneous tissue, destroying adjacent structures36 (Fig. 10).

Figure 10.

Histopathologic characteristics of syringoid carcinoma. A, Panoramic view showing a poorly circumscribed tumor invading the full thickness of the dermis. B, The neoplasm is formed by small ductal structures immersed in a sclerotic stroma. C, These ductal structures are lined with a layer of epithelial cells, some of which have an epithelial tadpole shape. D, High-magnification view of epithelial cells lining the ducts with no signs of cellular atypia. (Hematoxylin-eosin, original magnification ×10 [A], ×40 [B], ×200 [C], ×400 [D]).

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Porocarcinoma affects adults and elderly patients. Its most common presentation is a warty or sometimes ulcerated nodular or tumor lesion on the lower extremities (Fig. 9). Most porocarcinomas are de novo tumors, although there have been reports of malignant transformation of a long-standing poroma.

Histopathologically, porocarcinoma has typical architectural features of malignancy, with an asymmetric, poorly circumscribed tumor of varying shapes and sizes. The tumor is composed of 2 types of neoplastic cells: poroid and cuticular. Some of the neoplastic aggregates feature small ductal structures surrounded by cuticular cells (Fig. 11). On occasions, the tumor may be so poorly differentiated that it is impossible to distinguish between the 2 cell types. Epidermotropism is common and in some cases is so marked that it is very difficult to determine histologically whether the porocarcinoma is a primary lesion or an epidermotropic metastasis.42

Figure 11.

Histopathologic characteristics of porocarcinoma. A, Panoramic view showing an ulcerated tumor invading the full depth of the dermis. B, Neoplastic aggregates of varying shapes and sizes. C, Signs of ductal differentiation in some of the neoplastic aggregates. D, Detail of small ducts lined by cuticular cells. (Hematoxylin-eosin, original magnification ×10 [A], ×40 [B], ×200 [C], ×400 [D]).

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Microcystic adnexal carcinoma is a slow-growing tumor that preferentially affects the skin in the nasolabial and periorbital areas.45 It presents as a firm solitary nodule or plaque with a normal, atrophic, scaling, or on rare occasions, ulcerated surface.

Histopathologically, microcystic adnexal carcinoma penetrates into the deep dermis (Fig. 12) and frequently invades the subcutaneous tissue and sometimes even the underlying fascia and skeletal muscle. Perineural invasion is common in deep components of the lesion. Microcystic adnexal carcinoma has 3 distinct components arranged in horizontal layers. The surface areas contain cystic structures surrounded by squamous eosinophilic and/or pale cells, while the central layers contain solid islands of pale or eosinophilic cells of varying shapes and sizes interspersed with small, round ductal structures immersed in a sclerotic stroma. The deep layers, in turn, contain long tubular structures filled with homogeneous eosinophilic material. All these epithelial structures are immersed in a densely desmoplastic or sclerotic stroma.45

Figure 12.

Histopathologic characteristics of microcystic adnexal carcinoma. A, Panoramic view showing a tumor invading the full thickness of the dermis. B, Solid aggregates and small keratin-containing cysts. C, Note the tiny ductal structures in some of the neoplastic aggregates. D, Detail of small ductal structures in some of the neoplastic aggregates. (Hematoxylin-eosin, original magnification ×10 [A], ×40 [B], ×200 [C], ×400 [D]).

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Adenoid cystic carcinoma appears as a solitary dermal nodule or as multiple nodules that converge to form an indurated plaque that frequently invades the subcutaneous tissue and is fixed to the deep layers. Its most common location is the scalp, but it can occur in other parts of the body.

Histopathologically, primary adenoid cystic carcinoma appears as a poorly circumscribed tumor with aggregates of epithelial cells invading the deep layers. These aggregates, which are composed of basaloid cells, vary greatly in size and shape from one area to the next (Fig. 13) and almost always display perineural and/or endoneural invasion in the deep components of the tumor. The neoplastic cells form an alternating solid and cribriform pattern. Basement membrane deposits are frequently seen throughout the thickness of the tumor.49

Figure 13.

Histopathologic characteristics of adenoid cystic carcinoma. A, Panoramic view showing a poorly circumscribed tumor invading the subcutaneous facia, B, Higher-magnification view showing an adenoid cystic pattern in the neoplastic cells. C, Neoplastic aggregates of varying shapes and sizes with an adenoid cystic pattern. D, Higher-magnification view of neoplastic cells. (Hematoxylin-eosin, original magnification ×10 [A], ×40 [B], ×200 [C], ×400 [D]).

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Primary cutaneous mucinous carcinoma is somewhat more common in men and is almost always located on the head. It generally presents as a solitary nodule. The epidermal surface varies in appearance but ulcers are rare. Transillumination can be of considerable diagnostic aid as lesions with tumor stroma containing large amounts of mucin are seen as transparent.

Histopathologically, primary cutaneous mucinous carcinoma has a highly characteristic architecture formed by small islands of neoplastic basaloid cells surrounded by pools of mucin separated by thin connective septae causing compartmentalization of the tumor (Fig. 14). Occasional findings include neoplastic epithelial aggregates in the deep dermis or subcutaneous tissue located at some distance from the main tumor component. This separation explains why mucinous carcinoma tends to persist following incomplete surgical excision.

Figure 14.

Histopathologic characteristics of mucinous carcinoma. A, Panoramic view showing a tumor with abundant myxoid stroma. B, Thin walls of connective tissue compartmentalizing the tumor. C, The neoplastic cells are basaloid cells and are surrounded by myxoid stroma. D, Higher-magnification view of the neoplastic cells. (Hematoxylin-eosin, original magnification ×10 [A], ×40 [B], ×200 [C], ×400 [D]).

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Primary cutaneous mucinous carcinoma is rare, and most cases involving the skin are metastases from other sites. There are currently no histopathologic or immunohistochemical techniques for distinguishing a primary cutaneous mucinous carcinoma from a metastasis. This distinction, however, is very important as cutaneous metastases from mucinous carcinoma indicate a very poor prognosis, while primary cutaneous tumors generally have an indolent biologic behavior, although they can metastasize to the regional lymph nodes. All patients with cutaneous mucinous carcinoma must undergo full evaluation to rule out metastasis from a visceral mucinous carcinoma, in particular those involving the breast or colon. Recent studies have suggested that primary cutaneous mucinous carcinoma and cutaneous metastases may have a different cytokeratin pattern.52

Signet-ring cell carcinoma is a rare tumor that largely affects elderly patients. It occurs mainly on the eyelids but it can also affect the axillae. It presents as a nodule or as diffuse thickening of the skin, a sign that is often interpreted as an inflammatory process.

Signet-ring neoplastic cells are the most distinctive finding in this tumor (Fig. 15). The cells are relatively monomorphic and show no evident atypia. As a result, they may be misinterpreted as squamous histiocytes mimicking an inflammatory process.54 The tumor is formed by cords of cells, small solid islands, and even some neoplastic cells immersed in a sclerotic stroma.

Figure 15.

Histopathologic characteristics of signet-ring cell carcinoma of the eyelid. A, Panoramic view showing a poorly circumscribed tumor invading the full thickness of the dermis. B, The tumor is formed by isolated cells scattered through the dermis. C, Note the myxoid stroma in some areas of the tumor. D, High-magnification view of neoplastic cells with a signet-ring morphology. (Hematoxylin-eosin, original magnification ×10 [A], ×40 [B], ×200 [C], ×400 [D]).

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Before establishing a diagnosis of primary signet-ring cell carcinoma, it is necessary to rule out eyelid metastasis from a primary tumor in another location.

Extramammary Paget disease is more common in elderly women. It presents as an erythematous macule or plaque with clear borders and a scaling surface, and is preferentially located in the genital area.

Histopathologically, extramammary Paget disease is characterized by intraepithelial Paget cells, which are large cells with a wide, pale cytoplasm and a round, pleomorphic nucleus containing prominent nucleoli. The cells may show occasional signs of cytoplasmic vacuolization and even intraepidermal glandular formations. They have a characteristic distribution marked by small groups of isolated cells scattered through the layers of the epidermis and the adnexa, forming a pagetoid pattern (Fig. 16).

Figure 16.

Histopathologic characteristics of extramammary Paget disease. A, Panoramic view showing an intraepidermal lesion. B, The tumor is formed by isolated neoplastic cells scattered through the dermis. C, Note the pleomorphic nucleus and abundant pale cytoplasm in the neoplastic cells. D, Detail of neoplastic cells scattered through the epidermis. (Hematoxylin-eosin, original magnification ×10 [A], ×40 [B], ×200 [C], ×400 [D]).

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The authors declare that they have no conflicts of interest.