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Vulvar adnexal lesions: a 32-year, single-institution review from Massachusetts General Hospital.

The vulva consists of the labia majora, labia minora, clitoris, vestibule of the vagina, bulb of the vestibule, and a variety of glandular structures. The lateral aspect of the labia majora is covered by hair-bearing skin containing sweat glands, whereas the medial aspect is covered by keratinized or modified mucous membrane. The modified mucous membrane of the labia minor contains apocrine glands and ectopic sebaceous glands. Other glandular elements that are present in the vulva include the Skene glands (paraurethral glands), the Bartholin glands (mucus producing vestibular glands), and minor vestibular glands. (1) Mammary-type tissue in the vulva was first described by in 1892 by Hartung. (2) Previously thought to represent ectopic breast tissue, anogenital mammary-like glands are now regarded as normal structures at the anogenital site and are typically found in the sulcus between the labia minora and majora. (2,3) The superficial portion of the gland's excretory duct possesses an outer myoepithelial layer and luminal epithelial cells with apocrine features. (4) As the duct enters the epidermis, the myoepithelial layer is lost, and it is lined by squamous epithelium. (4) Toker cells (clear cells that may occur singly and in small clusters in the lower epidermis) may be apparent within the ductal epithelium at the site of insertion. (5) These Toker cells, also a normal constituent of the nipple and highlighted by cytokeratin 7, were first documented in the vulva by Willman et al. (6)

Because the vulva contains a high density of apocrine and anogenital mammary-like glands relative to eccrine glands and pilosebaceous units, we suspect that the spectrum of neoplasms identified in the vulvar region would reflect the relative frequency of these structures.


This study has been approved by the Massachusetts General Hospital institutional review board (No. 2011-P-2489). Archival materials of all benign and malignant adnexal lesions of the vulva diagnosed between 1978 and 2010 were retrieved from the pathology files of the Massachusetts General Hospital (Boston). Age, sex, tumor site, tumor size, and clinical follow-up information (such as local recurrence or metastasis) were extracted from the patients' medical records. All patient data were de-identified. The histologic sections of all cases were reexamined, and the diagnoses were confirmed.


A total of 189 vulvar adnexal lesions were identified (Tables 1 and 2). Benign lesions constituted 70% (133 of 189) of the cases (Table 1), with patient ages ranging from 12 to 80 years. Hidradenoma papilliferum was the most common (80 cases; 60%), followed by syringoma (29 cases; 22%), and various types of cysts (12 cases; 10%). These were followed in frequency by 3 cases (2%) of poroma, 2 cases (1.5%) of pilomatricoma, and 2 cases (1.5%) of spiradenoma; single cases of tubular adenoma, hidradenoma, cylindroma, sebaceoma, and trichoepithelioma (0.8% each) were identified. No cases (0%) of chondroid syringoma, steatocystoma, sebaceous hyperplasia, and sebaceous adenoma were found.

The remaining 30% (56 of 189) of cases were malignant lesions (Table 2), with the patient ages ranging from 36 to 92 years. Primary extramammary Paget disease (EMPD) was the most common (49 of 56 cases; 88%), and 29% (14 of 49) of EMPD cases were associated with an invasive component. Cases of secondary extramammary Paget disease were excluded in this series. Also identified were 2 cases (4%) of basal cell carcinoma (BCC), 2 cases (4%) of sebaceous carcinomas, and rare cases (n = 1 each) of apocrine carcinoma, spiradenocarcinoma, and adenoid cystic carcinoma (2% each). No cases (0%) of hidradenocarcinoma papilliferum, porocarcinoma, eccrine carcinoma, cylindrocarcinoma, hidradenocarcinoma, malignant chondroid syringoma, mucinous carcinoma, and adenocarcinoma of mammary-like glands were found.



Vulvar epithelial cysts are derived from a variety of resident structures. Those thought to arise from remnants of urogenital sinus include urogenital sinus cysts, major (Bartholin gland) and minor vestibular gland cysts, paraurethral (Skene gland) cysts, Wolffian-like duct cyst, and cysts of canal of Nuck. (7) Cysts derived from the overlying epidermis, hair follicles, and apocrine glands include epidermoid cysts, pilar or trichilemmal cysts, dermoid cysts, and hidrocystomas. Less-common entities include steatocystomas and cysts of anogenital mammary-like glands (previously reported as milk cysts of the supernumerary mammary glands). Chuang et al (8) reported multiple pigmented follicular cysts of the vulva, characterized by a stratified squamous epithelium with epidermoid keratinization containing multiple pigmented hair shafts and laminated keratin. Rare examples of apocrine cystadenoma and pigmented hidrocystoma derived from vulvar eccrine secretory coils have been reported by Glusac (9) and Kamishima, (10) respectively. We found cysts to be the third mostcommon type of benign vulvar adnexal lesions, consisting of rare cases of epidermoid cysts, pilar/trichilemmal cysts, dermoid cysts (Figure 1), and hidrocystomas.


Sebaceous Hyperplasia.--Sebaceous hyperplasia of the vulva is rare, with the literature comprising case reports. (11-17) This hyperplastic process is distinct from Fordyce spots, which are normally present on the labia minora. Unlike sebaceous hyperplasia, Fordyce spots involute after menopause and may be destroyed by inflammatory conditions, such as lichen sclerosus. Histopathologically, sebaceous hyperplasia is characterized as large, mature sebaceous lobules grouped around a central dilated duct, whereas Fordyce spots represent ectopic sebaceous glands without attached follicles. No cases of sebaceous hyperplasia were identified in this review.

Sebaceous Adenoma, Sebaceoma, and Sebaceous Carcinoma.--Extraocular sebaceous carcinoma most often occurs on the head and neck region and is less commonly seen at genital sites. Although sebaceous glands are abundant and may be prominent on the vulva, only a few cases of vulvar sebaceous carcinoma have been reported. (18-24) The case reported by Jacobs et al (19) was associated with colonic adenocarcinoma, likely in the setting of Muir-Torre syndrome. Two cases were associated with overlying Bowen disease. (19,22) We identified 2 additional cases (4% of the 56 malignant cases) of sebaceous carcinoma of the vulva, neither of which were associated with Muir-Torre syndrome. No cases of sebaceous adenomas were identified in this series.

Muir-Torre syndrome is an autosomal-dominant syndrome defined by the presence of at least one sebaceous gland tumor and the presence of an internal malignancy. (25) Although most patients have only one malignancy, 2 or 3 different malignancies can be seen in half of the cases. (26) The most-common visceral neoplasm is colorectal carcinoma (51%). Loss of immunoreactivity for MSH2, MLH1, and MSH6 gene products can serve as screening test for potential underlying genetic defect. (27) Recent research has shown that a screening panel should include at least MSH6 and PMS2. (28)

Histopathologically, sebaceous carcinoma is characterized by an infiltrative tumor composed of pleomorphic basaloid cells with focal sebaceous differentiation. Ductal structures with an eosinophilic cuticle, characteristic of sebaceous ducts, may be seen in well-differentiated sebaceous tumors. Vascular and perineural invasion can be identified. When a tumor exhibits multiple nests of basaloid cells with scattered mitoses but lacks the atypia sufficient for a diagnosis of sebaceous carcinoma, it is classified as a sebaceoma (Figure 2, A and B). Of 56 malignancies, we identified one case (2%) of sebaceoma, which has not been previously reported in the vulva, to our knowledge. Recently, adipophilin has been shown to be a sensitive marker for sebaceous carcinoma. (29) A panel of adipophilin and androgen receptor is helpful in the differential diagnosis of sebaceous carcinoma versus squamous cell carcinoma. (30,31) Nuclear p53 staining was found to be significantly associated with the diagnosis of sebaceous carcinoma compared with benign sebaceous lesions. (32)



Trichofolliculoma.--To date, vulvar trichofolliculoma in the literature is limited to a single series citing 3 cases. (33) All 3 were associated with vulvar intraepithelial neoplasia. The characteristic histopathologic findings include a central, cystically dilated follicle with radiating hair follicles. No cases of trichofolliculoma or its sebaceous variant were identified in this review. Recent studies of trichofolliculoma has shown that these lesions are characterized by a proliferation of cytokeratin-[15.sup.+] hair-follicle stem cells. (34)

Trichoepithelioma.--Trichoepithelioma, a benign hair follicle tumor, is often found on the head and neck region but only rarely found in the hair-bearing skin of the vulva with only 4 previously reported cases. (35-38) We identified one case of vulvar trichoepithelioma (1% of benign vulvar adnexal neoplasms; Table 1). Histopathologically, it can simulate a basal cell carcinoma (Figure 3). Many studies, often conflicting, have sought to distinguish trichoepithelioma from basal cell carcinoma with immunohistochemistry. Often, a panel composed of CD10, cytokeratin 15, cytokeratin 20, and D2-40 is required to differentiate trichoepithelioma from BCC. (39) Recently, Sellheyer et al (40) demonstrated the promise of PHLDA-1 (pleckstrin homology-like domain family A member 1), a follicular stem cell marker, in confirming the diagnosis of trichoepithelioma in small biopsies. However, subsequent study has shown the limitation of this stain. (41)

Basal Cell Carcinoma.--Basal cell carcinoma is the most-common cutaneous cancer in the United States. (42) However, only approximately 300 cases of anogenital BCC have been reported, (42-47) to our knowledge, accounting for less than 1% of all BCCs (45) and 3% of all vulvar cancer. (44) The median age appears to be the seventh decade. (44,47) Only rarely do the patients develop nodal metastases. The occurrence of BCC in non-sun-exposed areas raises the possibility of other etiologic agents, such as chronic irritation, chronic infection, trauma, irradiation, and arsenical compounds. (46) Human papilloma virus testing by in situ hybridization for serotypes 6, 11, 16, 18, 31, 33, 51 was reported negative in 5 tested cases. (47) This review identified 2 cases of vulvar BCC (4% of malignant vulvar adnexal neoplasms), both of which were nodular types, the most-common histopathologic subtype (Figure 4). (47)

Germline mutations in the patched or patched 1 (PTCH) gene, a tumor suppressor gene, and the human homolog of the Drosophila patched gene, on band 9q22.3 were demonstrated in BCCs of the basal cell nevus syndrome (60%-70%) as well as in sporadic BCCs. (48,49)

Pilomatricoma and Pilomatrical Carcinoma.--Pilomatricoma is a benign neoplasm composed of basaloid and shadow cells that characterize differentiation toward the hair matrix. In a review of 346 cases, pilomatricoma of the vulva was not documented. (50) Pilomatrical carcinoma, a malignant counterpart of pilomatricoma, is a rare entity, and a case has been reported involving the clitoris. (51) Mutations in exon 3 of the CTNNB1 ([beta]-catenin) gene have been documented in pilomatricoma, pilomatrical carcinoma, and BCC with matrical differentiation. (52,53) We identified 2 of the 56 malignant cases (4%) of pilomatricoma in our series.








Syringoma.--Syringomas are benign eccrine neoplasms that most commonly occur on the eyelid and malar region of women. (54,55) Originally described in 1874 by Kaposi, vulvar involvement was not reported until 1971 and has been regarded as a rare manifestation. (55) Since then, isolated cases and small case series of syringomas involving the genital region have been reported. (54-67) In a Taiwanese series of 18 cases of vulvar syringoma, lesions were most common in women during the third decade, most often (11 of 18; 61%) presenting as multiple, flesh-colored or brownish papules on the labia majora. (54) Three (17%) presented with discrete, whitish cystic papules. (54) Pruritus was the most common presenting symptom. (54)

Although some researchers have hypothesized the development of syringoma to be under hormonal influence, (56,57) no studies to date have demonstrated staining for estrogen receptor or progesterone receptor, to our knowledge. (54,58) Of interest, autoimmune acrosyringitis has been proposed as a cause of eruptive syringoma in a case report. (59) Reported effective treatment options for vulvar syringomas include carbon dioxide laser treatment, (54,60) cryotherapy, (61) electrosurgery, (62) and excision. (57)

We identified 29 of the 133 benign cases (22%) during a 32-year period (Table 1). Not infrequently, vulvar syringoma was seemingly an incidental finding (41%; 12 of 29 cases) and was a secondary diagnosis in 4 cases of melanocytic nevi (3 atypical, 1 congenital) (Figure 5), 4 cases of lichen sclerosus (Figure 6), 3 cases of lichen simplex chronicus, as well as single cases of squamous cell carcinoma, EMPD, condyloma, seborrheic keratosis, lymphangioma, and epidermoid cyst. None of the patients (0%) were identified as having extragenital involvement. In contrast to periorbital syringomas, none of these patients (0%) were known to have a family history of syringoma or Down syndrome; no exacerbation during menstruation, pregnancy, or warmer season was shown. Because most vulvar syringomas were asymptomatic, and given the frequency with which they were a seemingly incidental finding, either being detected during routine gynecologic examination or remaining unrecognized by patient and physician alike, the observations in this case series suggest that the prevalence of vulvar syringoma may be underestimated. Histopathologically, the deep and plaque types can be mistaken for microcystic adnexal carcinoma. (68,69) We did not identify any unusual variants of syringoma, such as giant, plaque-like, or clear cell variants.

Hidradenoma and Hidradenocarcinoma.--Clear cell hidradenoma, also known as eccrine acrospiroma, usually presents as a solid and cystic nodule with no site predilection, although it is only rarely reported to occur on the vulva. (70,71) Similarly, only one case of hidradenoma was identified in this review. Histopathologically, hidradenoma is characterized by multilobulated, circumscribed, yet unencapsulated, tumor. The tumor cells are diverse and can be clear, eosinophilic, squamoid/epidermoid, mucinous, oxyphilic/oncocytic, and transitional/intermediate. (72) When focal infiltrative architecture and increased mitotic figures are seen, it is classified as atypical hidradenoma. (73) Otherwise, hidradenocarcinomas are typically characterized by infiltrative growth pattern, deep extension, necrosis, nuclear pleomorphism, and greater than 4 mitoses per 10 high-power fields. (73) Although in some rare instances, metastasizing hidradenocarcinomas do not show these histopathologic features. (74) Only rarely has vulvar hidradenocarcinoma been reported; accordingly, no hidradenocarcinomas (0%) were identified in this series. (75,76)

Approximately 50% of hidradenomas possess the t(11;19) translocation. (74) ERBB2 (formerly Her2/neu) amplification has been reported in a case of metastasizing hidradenocarcinoma (77); however, that finding has not been confirmed by subsequent studies. (74,78,79) Although atypical and malignant hidradenomas express EGFR, only occasional cases with gene polysomy and no gene amplification were found. (79,80) In rare cases of hidradenocarcinomas mutations of TP53, (74,79,81) PIK3CA, (79) and AKT-1 (79) have been documented.

Poroma and Porocarcinoma.--Although eccrine poroma, a tumor derived from the acrosyringium, most often presents on plantar or palmar skin, it may occur at any site containing sweat glands. (82) In this review, we identified 3 cases of vulvar poroma (2% of benign vulvar adnexal neoplasms) (Figure 7). Despite rare cases of vulvar porocarcinomas reported in the literature, (83-86) its benign counterpart, the poroma, has not been previously documented as occurring on the vulva, to our knowledge. Vulvar porocarcinoma appears to most often affect women in the sixth decade, and, similar to porocarcinomas at other sites, vulvar porocarcinomas are associated with frequent nodal metastases. (83-86) The main histologic mimic is squamous cell carcinoma, and a panel of cytokeratin 19 and cytokeratin 7 is considered helpful. (87) Regarding molecular studies, TP53 and PIK3CA mutations and EGFR gene polysomy have been documented in rare cases of porocarcinomas. (78,79,81)

Eccrine Carcinoma.--The overlapping features of eccrine carcinoma and adenocarcinoma of mammary-like glands make this distinction challenging. (4,88) Furthermore, both entities can express estrogen receptor, progesterone receptor, or gross cystic disease fluid protein-15. (88,89) Although slow growing, eccrine carcinomas tend to recur and to exhibit regional or distant metastases. (90) Rare cases have been reported in the vulva. (91)

Hidradenoma Papilliferum, Tubular Adenoma, and Hidradenocarcinoma Papilliferum.--Hidradenoma papilliferum was first reported by Worth in 1878 and characteristically occurs in the vulvar and perianal regions. (92) Initially thought to be derived from the apocrine glands, (72) subsequent reports suggest hidradenoma papilliferum (and tubular adenoma) to be derived from anogenital mammary like glands. (93,94) Therefore, the term mammary-like gland adenoma of the vulva has been proposed. (95) The sites of involvement include labia minora (50%), labia majora (40%), fourchette (7%), and clitoris (3%). (95) This distribution mirrors that of anogenital mammary-like glands. Although human papillomavirus types 16, 31, 33, 53, and 56 have been identified within lesional tissue, the virus does not appear to play a causative role. (96)

In our series, hidradenoma papilliferum was the most-common benign vulvar adnexal neoplasm, accounting for 60% of the benign lesions and 42% of the total vulvar adnexal neoplasms (Table 1). Histopathologically, the tumor exhibits both a papillary and glandular architecture. The epithelial cells are typically columnar, with pale eosinophilic cytoplasm, and are surrounded by a thin myoepithelial layer (Figure 8). Oncocytic metaplasia, clear cell changes, predominantly solid-growth cystic changes, and others can be seen. (4,96)

The literature cites 5 cases of ductal carcinoma in situ arising in association with hidradenoma papilliferum. (97-100) Histopathologically, these tumors are described as possessing foci of pleomorphic epithelial cells with hyperchromatic nuclei and abnormal mitotic figures. However, the retention of a myoepithelial layer is indicative of its in situ nature. (98,100)

Spiradenoma and Spiradenocarcinoma.--Spiradenoma typically presents as a painful nodule on the head and neck, trunk, or extremities. (101) Although vulvar spiradenoma had not been reported, we identified 2 such cases (1% of benign vulvar adnexal neoplasms) (Table 1). Histologically, this well-circumscribed tumor is composed of 2 cell populations: a central cluster of page large cells surrounded by small, dark, basaloid cells, with hyperchromatic nuclei (Figure 9, A and B). First reported in 1971 by Dabsk, (102) spiradenocarcinoma is a rare tumor occurring in adults, with no gender predilection, and most often occurring on the ventral aspect of the upper body. (103,104) To date, approximately 53 cases have been reported, and only one case was documented as arising in the vulva. (105-107) The clinical course varies, but metastases to regional lymph nodes and distant organs, such as bones and lungs, have been reported. (103,104) This review identified one additional case of vulvar spiradenocarcinoma; at 6 years of follow-up, the patient has no evidence of recurrent or metastatic disease. Histopathologically, the malignant component is composed of nodules of tumor in the dermis and subcutaneous fat. The benign spiradenoma component is comprised of 2 cell types: small and dark cells at the periphery, and larger and paler cells in the center. There is often an abrupt transition to high-grade carcinoma composed of atypical epithelioid cells with prominent nucleoli, marked pleomorphism, and high mitotic rate (Figure 10). A second pattern is characterized by replacement by atypical basaloid cells with increased mitotic rate. (104) Histopathologic features of malignant transformation includes loss of the characteristic 2-cell population, a sheetlike growth pattern, nuclear hyperchromasia and pleomorphism, excessive mitotic activity, and an infiltrative border. (104)

Cylindroma and Cylindrocarcinoma.--Cylindromas are typically found on the head and neck region. (108) In the vulva, cylindroma has been documented in rare publications. (108) Similarly, we identified a single case in this review (1% of benign vulvar adnexal neoplasms; Table 1). Its malignant counterpart, cylindrocarcinoma, has been documented in one rare case at this site. (109) Histopathologically, it is characterized by a poorly circumscribed tumor composed of islands and cords of basaloid cells surrounded by eosinophilic hyaline materials.

Multiple cylindromas accompanied by spiradenomas or trichoepitheliomas or both are found in inherited syndromes, such as Brooke-Spiegler syndrome, familial cylindromatosis, and multiple familial trichoepithelioma syndrome. (110) The involved gene in all of these syndromes is the CYLD tumor suppressor gene located on band 16q12-13. (110) The TP53 mutation has been reported in 2 cases of Spiradenocarcinomas (81) and one case of malignant cylindroma. (79)

Chondroid Syringoma and Malignant Chondroid Syringoma.--Chondroid syringoma, also known as benign mixed tumor, is a rare tumor of the vulva, with only a few cases reported in the literature. (111-115) In the vulva, these lesions are thought to arise from underlying sweat glands or Bartholin glands. (111) Histopathologically, the tumor contains a mixture of epithelial and myoepithelial cells associated with a myxoid or cartilaginous stroma. (113) In the skin, there are 2 types of chondroid syringoma--apocrine and eccrine. (116) The malignant counterpart, malignant chondroid syringoma, is characterized by infiltrative growth, greater cellularity, nuclear pleomorphism, mitotic activity, and necrosis. (117) These neoplasms can recur and have the potential to metastasize to regional lymph nodes and distant sites. We did not identify any cases of benign or malignant vulvar chondroid syringomas in this review.

Apocrine Carcinoma.--Cutaneous apocrine carcinomas are rare, and only rare cases of vulvar apocrine carcinoma have been reported in the literature. (118-121) It has been postulated that some of these lesions originated from the anogenital mammary-like glands. We identified a single case, which also exhibited metastatic disease to regional lymph nodes as documented in previously reported vulvar cases. (119-121) Histopathologically, there is a mixture of patterns, including papillary, trabecular, and solid patterns. (118) The tumor cells are often polygonal and with eosinophilic cytoplasm (Figure 11). Studies have shown a strong correlation of androgen receptor expression in cutaneous apocrine carcinoma, raising the potential for antiandrogen therapy. (79,118)

Extramammary Paget Disease.--Extramammary Paget disease can be either primary or secondary. Primary EMPD can be either an intraepithelial neoplasm with or without an associated invasive component or a manifestation of an underlying primary adenocarcinoma. The implicated cells of origin for primary EMPD include apocrine glands, anogenital mammary-like glands, vulvar Toker cells, or possibly, pluripotential stem cells. (4,122,123) In contrast, secondary EMPD arises from an underlying carcinoma of genitourinary (bladder) or gastrointestinal origin (distal colon or rectum). Primary EMPD most often affects women in their seventh decade. (124) The vulva is the most frequently involved site, followed by labia majora, then labia minora, then the clitoris. (124) Primary EMPD is slowly progressive and rarely metastasizes, contrary to the secondary form. Noninvasive EMPD has an excellent prognosis. (125) The frequency of invasion in EMPD was reported as 0% to 48% of cases in one large meta-analysis. (126) Kodama et al (127) reported 30% (9 of their 30 cases) had invasion, similar to 29% (14 of 49 cases) observed in our series, whereas Shaco-Levy et al (124) reported 18% in their series (10 of 56 cases). Studies have shown conflicting data regarding the presence of invasion and prognosis. (127,128)

Forty-nine cases of EMPD were identified in this review (87.5% of the 56 cases of malignant vulvar adnexal neoplasms and 25.9% of the total 189 cases of vulvar adnexal neoplasms); 14 of these 49 cases (29%) were associated with an invasive component. All cases (100%) were interpreted to represent primary EMPD, and no patients (0%) were noted to have metastatic disease.






The histopathologic features of both primary and secondary forms of EMPD are similar, characterized by large, pale cells arranged singly or in clusters within the epidermis (Figure 12). Involvement of adnexa, most commonly hair follicles and eccrine ducts, is frequently seen in EMPD. In a recent study of 56 patients, Shaco-Levy et al (124) reported that a panel of pancytokeratin, CK7, CEA, and EMA labeled 100% of primary EMPD cases, whereas none of those cases stained with S100, HMB-45, and MART-1, thereby distinguishing EMPD from malignant melanoma. Because secondary EMPD is associated with a worse prognosis, it is important to distinguish the 2 forms. In a study of 98 specimens from 61 patients, Perrotto et al (129) demonstrated that CDX2 stained 100% of the cases associated with colorectal adenocarcinoma but only 33% of the primary cases. Other studies have shown CK20 to be useful in identifying secondary EMPD arising from a colorectal primary. (130) Similarly, uroplakin III has been shown to be of help in identif)ying secondary EMPD arising from a urothelial primary. (131)

Extramammary Paget disease expresses androgen receptor but often lacks expression of estrogen receptor and progesterone receptor. (132) A high proportion of cases (32%) have been found to demonstrate overexpression of ERBB2 (133); however, gene amplification was not seen on fluorescence in situ hybridization. (134)

Mammary-Like Anogenital Glands Adenocarcinoma of Mammary-Like Glands.--First

reported in 1936 by Greene, (135) there have been approximately 30 to 40 cases of adenocarcinoma of mammary-like glands reported in the literature to date. (4,88,89,136-138) The tumor exhibits an aggressive behavior, with 60% (12 of 20) of patients having regional lymph node metastasis at the time of presentation. (88) The presence of a transition zone between normal mammary-like glands and the carcinoma component is necessary to establish a diagnosis. The histopathology of these tumors varies from predominantly ductal to lobular, mixed ductal and lobular, tubulolobular, mucinous, and adenoid cysticlike. (88,136,137) No examples of adenocarcinoma of mammary-like glands were identified in this review.


Adenoid Cystic Carcinoma.--Although vulvar sweat gland carcinoma is very rare, accounting for less than 1% of all malignant vulvar tumors, adenoid cystic carcinoma accounts for approximately 20% to 25% of all Bartholin gland malignancies. (139-142) Complex chromosomal changes have been reported in one case of adenoid cystic carcinoma of the Bartholin gland. (141) Rarely, the tumor can arise from Skene glands. (143) Despite the tumor's tendency to be slow-growing, there is marked predilection for perineural invasion. A high rate of recurrence and metastasis to regional lymph nodes, lungs, and bones can occur. The 10year survival rate is 59%. (142) The type of histopathologic variant, whether classic, tubular, or mixed (cribriform, tubular, and solid) has not been found to be predictive for survival (Figure 13). (144)

Mucinous Adenocarcinoma.--Mucinous adenocarcinoma has a slow growth in contrast to other adnexal carcinomas, which has been postulated to be due to the pressure exerted by the extracellular mucin. (145) Mucinous adenocarcinoma of the vulva is very rare and is reported to occur as a pure mucinous carcinoma. (146,147) It can arise in association with EMPD. (148) The histopathologic differential diagnosis includes metastatic carcinoma to the vulva from various sites, including the genitourinary and gastrointestinal tracts. This review did not identify any cases of vulvar mucinous adenocarcinoma. Results of ERBB2 stain are negative in a few studied mucinous adenocarcinomas. (149)


The spectrum of various vulvar adnexal lesions appears to reflect the relative frequency of the underlying glandular elements. Hidradenoma papilliferum and EMPD were the most common benign and malignant adnexal neoplasms, respectively. In this review, we also identified several benign entities that have not been previously reported on the vulva, to our knowledge, namely, pilomatricoma, poroma, spiradenoma, and sebaceoma.

Caption: Figure 1. Dermoid cyst. Pilosebaceous units are shown inserting into the wall of a cyst lined by stratified, squamous epithelium and containing loosely packed, keratin fragments (hematoxylin-eosin, original magnification X100).

Caption: Figure 2. Sebaceoma. A, A well-circumscribed tumor is in the dermis. B, At higher magnification, nests of basaloid cells are shown admixed with sebaceous cells (hematoxylin-eosin, original magnifications X40 [A] and X100 [B]).

Caption: Figure 3. Trichoepithelioma. The tumor comprises basaloid cells and rudimentary follicular structures (hematoxylin-eosin, original magnification

Caption: Figure 4. Basal cell carcinoma. A nodular tumor composed of basaloid cells is shown, with peripheral palisade and extracellular mucin (hematoxylin-eosin, original magnification X40).

Caption: Figure 5. Syringoma and associated lichen sclerosus. Beneath superficial dermal sclerosis and a bandlike infiltrate, a proliferation of ductlike structures is noted (hematoxylin-eosin, original magnification X40).

Caption: Figure 6. Syringoma and associated lentiginous compound dysplastic nevus. Above a focus of syringoma, a proliferation of mildly atypical melanocytes is arranged in single cells, in small nests at the basal layer of epidermis, and in small nests in the dermis (hematoxylin-eosin, original magnification X100).

Caption: Figure 7. Poroma. Well-circumscribed nests of basaloid cells exhibiting ductal differentiation are shown within the epidermis (hematoxylin-eosin, original magnification X100).

Caption: Figure 8. Hidradenoma papilliferum. Both papillary and trabecular architecture are noted (hematoxylin-eosin, original magnification X100).

Caption: Figure 9. Spiradenoma. A, A well-circumscribed tumor is shown. B, At higher magnification, 2 cell types are noted--outer, darker cells and inner, lighter ones (hematoxylin-eosin, original magnifications X40 [A] andX200 [B]).

Caption: Figure 10. Spiradenocarcinoma. A proliferation of atypical epithelial cells associated with a large zone of necrosis is shown (hematoxylin-eosin, original magnification X100).

Caption: Figure 11. Apocrine carcinoma. Cribriform architecture and polygonal neoplastic cells with eosinophilic cytoplasm are characteristic features of apocrine carcinoma (hematoxylin-eosin, original magnification X200).

Caption: Figure 12. Extramammary Paget disease. An intraepidermal proliferation shows singly dispersed, epithelioid neoplastic cells containing cytoplasmic mucin (hematoxylin-eosin, original magnification X100).

Caption: Figure 13. Adenoid cystic carcinoma. Strandlike proliferation and cribriform architecture are noted (hematoxylin-eosin, original magnification X200).


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Gabrielle M. Baker, MD; M. Angelica Selim, MD; Mai P. Hoang, MD

Accepted for publication November 9, 2012.

From the Department of Pathology, Harvard Medical School and Massachusetts General Hospital, Boston (Drs Baker and Hoang); and the Department of Pathology, Duke University Medical Center, Durham, North Carolina (Dr Selim).

The authors have no relevant financial interest in the products or companies described in this article.

Reprints: Mai P. Hoang, MD, Department of Pathology, Massachusetts General Hospital, 55 Fruit St, Warren 820, Boston, MA 02114 (e-mail:
Table 1. Summary of 133 Benign Vulvar
Adnexal Neoplasms (70.4%; N = 189)

                             Cases, No.
                            (% of Benign;     Age Range
                             % of Total)     (Median), y

Hidradenoma papilliferum   80 (60.2;42.3)    24-80 (50)
Syringoma                  29 (21.8; 15.3)   12-74 (51)
Cysts                      12 (9.9;6.3)      20-73 (51)
  Epidermoid                6 (4.5; 3.2)
  Pilar/ trichilemmal       4 (3.0; 2.1)
  Hidrocystoma              1 (0.8; 0.5)
  Dermoid cyst              1 (0.8; 0.5)
Pilomatricoma               2 (1.5; 1.1)     11-16 (13)
Poroma                      3 (2.3; 1.6)     27-77 (56)
Spiradenoma                 2 (1.5; 1.1)     60-71 (65.5)
Hidradenoma                 1 (0.8; 0.5)          73
Apocrine tubular adenoma    1 (0.8; 0.5)          60
Cylindroma                  1 (0.8; 0.5)          71
Sebaceoma                   1 (0.8; 0.5)          46
Trichoepithelioma           1 (0.8; 0.5)          64

Table 2. Summary of 56 Malignant Vulvar
Adnexal Neoplasms (29.6%; N = 189)

                              Cases, No.
                           (% of Malignant;    Age Range
Type                         % of Total)      (Median), y

EMPD, all cases             49 (87.5;25.9)    53-92 (75)
  EMPD, with invasive
  component                 14 (29.0;7.4)
Basal cell carcinoma         2 (3.6; 1.1)     80-82 (81)
Sebaceous carcinoma          2 (3.6; 1.1)         71
Adenoid cystic carcinoma     1 (1.8; 0.5)         36
Apocrine carcinoma           1 (1.8; 0.5)         69
Spiradenocarcinoma           1 (1.8; 0.5)         50

Abbreviation: EMPD, extramammary Paget disease.
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Title Annotation:Original Articles
Author:Baker, Gabrielle M.; Selim, M. Angelica; Hoang, Mai P.
Publication:Archives of Pathology & Laboratory Medicine
Article Type:Report
Geographic Code:1U1MA
Date:Sep 1, 2013
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