Search

We report a patient with multiple trichoepitheliomas whose biopsy material also demonstrated a range of other neoplasms with follicular differentiation, including small nodular trichoblastoma, small nodular basal cell carcinoma (BCC), and areas resembling infundibulocystic BCC/basaloid follicular hamartoma. These were all intimately associated with otherwise typical trichoepitheliomas that dominated the microscopic appearances. Peripheral blood and tumor tissues of the patient and his 2 daughters, who apparently had a milder phenotype, were studied for alterations in the CYLD and PTCH genes, but mutations or loss of heterozygosity was not found in either gene. The occurrence of multiple follicular neoplasms within a single lesion adds evidence that, although in most cases BCC and trichoblastoma are distinct lesions, the 2 neoplasms do encompass a morphological spectrum of follicular differentiation, which is probably more overtly expressed in syndromic patients.

The authors present a series of 24 malignant neoplasms arising in preexisting benign spiradenoma (20), cylindroma (2), and spiradenocylindroma (2). Nineteen patients (12 females, 7 males; age range, 41 to 92 y) had a solitary neoplasm (size range, 2.2 to 17.5 cm; median 4 cm), whereas the remaining 5 (4 females, 1 male; age range, 66 to 72 y) manifested clinical features of Brooke-Spiegler syndrome (BSS), an autosomal dominantly inherited disease characterized by widespread, small, benign neoplasms on which background larger malignant lesions appeared. Microscopically, all cases showed the residuum of a preexisting benign neoplasm. The malignant components of the lesions were variable and could be classified into 4 main patterns, occurring alone or in combination: 1) salivary gland type basal cell adenocarcinoma-like pattern, low-grade (BCAC-LG); 2) salivary gland type basal cell adenocarcinoma-like pattern, high-grade (BCAC-HG); 3) invasive adenocarcinoma, not otherwise specified (IAC-NOS); and 4) sarcomatoid (metaplastic) carcinoma. In 1 case of IAC-NOS, an in situ adenocarcinoma was also found, presumed to have evolved from an adjacent adenomatous and atypical adenomatous component. Cases harboring a sarcomatoid carcinoma featured a malignant epithelial component composed of varying combinations of BCAC-HG, BCAC-LG, IAC-NOS, or squamous cell carcinoma, whereas the sarcomatoid component appeared as either a pleomorphic or spindle-cell sarcoma. Additionally, in 2 cases there were foci of heterologous chondrosarcomatous differentiation and in 1 case there was rhabomyosarcomatous differentiation. Of the 21 patients with available follow-up (range, 3 mo-15 y; average 4.8 y; median 3.5 y), 10 were without evidence of disease, 1 was alive with metastatic disease, 1 was alive with BSS, 3 developed local recurrences, 4 had died of disease, and 2 were dead of other causes. The histologic pattern of the malignant neoplasm correlated to some extent with the clinical course. BCAC-LG neoplasms showed a less aggressive course, with local recurrences but no distant metastases, whereas the BCAC-HG neoplasms typically followed a highly aggressive course resulting in the death 3 of 6 patients with BCAC-HG. Patients with sarcomatoid carcinoma had a relatively good survival. Molecular genetic investigations revealed no mutations in the CYLD gene in the 4 sporadic cases investigated. One patient with BSS revealed a novel missense germline mutation in exon 14 (c. 1961T>A, p. V654E), whereas a living descendant of another deceased patient demonstrated a recurrent nonsense germline mutation in exon 20 (c. 2806C>T, p. R936X). Given the morphologic diversity and complexity of the neoplasms in question, we propose using a more specific terminology with the precise description of the neoplasm components, rather than generic and less informative terms such as "spiradenocarcinoma" or "carcinoma ex cylindroma."

We describe 11 poroid neoplasms with sebaceous differentiation, including a metaplastic (sarcomatoid) carcinoma arising in association with an apocrine poroma. Six lesions had the silhouette of a classical poroma, 3 of poroid hidradenoma and 1 of dermal duct tumor. In all cases, sebaceous differentiation was identified as clustered or solitary, mature sebocytes occurring mainly at the periphery of intradermal cellular aggregations, accompanied by sebaceous ducts. In one poroma, clusters of sebocytes were seen within intradermal aggregates and intraepidermally. In 1 of the 3 poroid hidradenomas, the eosinophilic cuticle lining the cyst was crenulated in foci associated with sebocytes. In none of the cases were there signs of follicular differentiation. One poroma, in addition to sebaceous differentiation, showed decapitation secretion in some ductular structures. The single carcinoma was an ulcerated oval to spindle cell neoplasm surrounded laterally by the residuum of a poroma containing groups of sebocytes. The epithelial islands of the poroma were prominently keratinized and blended gradually with the pleomorphic cells of the metaplastic carcinoma that immunohistochemically stained focally for cytokeratins and simultaneously showed strong vimentin expression. Our study supports previous findings that sebaceous differentiation can be identified not only in classical poroma but also in the related lesions known as dermal duct tumor and poroid hidradenoma. Occurrence of metaplastic carcinoma in association with apocrine poroma is a rare event which indicates the existence of a malignant counterpart of the latter entity, which can be descriptively referred to as "sarcomatoid apocrine porocarcinoma."

Syringocystadenoma papilliferum is a benign tumor most commonly located on the scalp or face, and it often arises within a nevus sebaceus of Jadassohn. We describe a 61-year-old man with syringocystadenoma papilliferum developing within a nevus sebaceus with sebaceous differentiation in an intradermal tubular apocrine component of the syringocystadenoma papilliferum. Although some adnexal neoplasms that develop in association with a nevus sebaceus may exhibit conjoint sebaceous, follicular, or apocrine differentiation, reflecting close embryological relations of the folliculosebaceous-apocrine unit, the feature we report on has not previously been described to the best of our knowledge.

Tubular adenoma (TA) and syringocystadenoma papilliferum (SCAP) may show histopathological overlap, with some lesions having features of both neoplasms (SCAP + TA). TA has been recently suggested to represent a carcinoma. Four observers blindly assessed 67 cases of TA, SCAP, and their lookalikes (poroma, apocrine adenoma, apocrine carcinoma; all lesions focally featuring a pseudopapillary pattern), and classified the lesions into one of four categories: (1) TA, (2) SCAP, (3) SCAP + TA, and (4) others. Lesions were also classified as benign or malignant. In only 29 cases was there unanimous agreement among the four observers, who classified 22 lesions as TA, three as SCAP, and four cases as others. Of the 38 cases where there was interobserver diagnostic variation, in 30, the diagnosis varied between TA or SCAP or SCAP + TA; the remainder fell in the others category. Analysis of the factors leading to interobserver variability indicated that diagnostic problems occurred when there were any of the following: epidermal acanthosis, papillomatosis, connection of the neoplastic tubules to the overlying epidermis and/or follicular infundibula, and plasma cell infiltration. These features accounted for the morphological overlap between TA and SCAP. All observers agreed that the lesions were benign; the only apocrine carcinoma included was recognized as such by all observers. From the study, it was concluded that TA may arise in the deep dermis without any epidermal connection, or, in other cases, it may be more superficially located with or without an epidermal connection. It may be reasonably inferred that, possibly as a response to infection, there may be accompanying plasma cells and variable acanthosis and papillomatosis, such that the appearances are those of "pure" SCAP, or lesions may have features "intermediate" or overlapping between TA and SCAP.

The authors report a small series of sebaceous carcinoma developing in nevus sebaceus of Jadassohn (also known as organoid nevus) and analyze similar cases reported in the literature. All of our patients were females (age range 57-71 years; median 60 years) who had the organoid nevus on the scalp, face, or nuchal area, the rest of which was recognized clinically and/or histologically. All sebaceous carcinomas manifested unquestionable architectural (asymmetry, invasive growth) and cytological features of a carcinoma (cellular and nuclear pleomorphism, plentiful atypical mitoses, necroses en masse), demonstrated unambiguous sebaceous differentiation in the form of mature sebocytes, and lacked other differentiations. The sebaceous carcinoma was always accompanied by other benign or malignant adnexal lesions such as sebaceoma, syringocystadenoma papilliferum, syringocystadenocarcinoma papilliferum, trichoblastoma, tricholemmoma, desmoplastic tricholemmoma, or syringoma. In three cases, prominent mucinous metaplasia of sweat ducts and glands was seen. In two of these cases, sweat ducts exhibited hyperplastic changes. The analysis of the previously published material and our cases indicates that sebaceous carcinoma arising in organoid nevus has a female predilection and tends to occur in elderly patients. It may involve any site where nevus sebaceus typically occurs. Clinically, the tumor presents as a solitary nodule, ulcerated tumor, or mass, often with a recent history of rapid growth. It may arise alone, but it occurs more frequently as part of multiple benign and malignant adnexal tumors. The lesion does not seem to be associated with Muir-Torre syndrome. The rest of organoid nevus is usually recognized both clinically and microscopically, although large tumors may overgrow and mask the nevus. The tumor seems to be a low-grade carcinoma in terms of clinical behavior.

Brooke-Spiegler syndrome is an autosomal dominantly inherited disease with predisposition to cutaneous adnexal neoplasms, most commonly cylindromas and trichoepitheliomas. We report a patient in whom 11 lesions were removed from the scalp and face for various reasons over a period of 3 years. The histopathological survey revealed a plethora of benign adnexal neoplasms showing apocrine, follicular, and sebaceous differentiation occurring independently and conjointly. The histopathological spectrum in our patient included cylindromas, spiradenomas, trichoepitheliomas, small nodular trichoblastomas, and lymphadenomas. Many lesions had hybrid features of two or more neoplasms. By far the most common composite tumor was spiradenocylindroma. Some spiradenocylindromas demonstrated prominent sebaceous or trichoblastomatous differentiation or both. We suggest the terms "sebaceous spiradenocylindroma" and "trichospiradenocylindroma" for these lesions. The occurrence of sebaceous and trichoblastic differentiation in spiradenocylindromas is a further proof that spiradenoma and cylindroma are not eccrine tumors but neoplasms of the folliculosebaceousapocrine unit.

We present three cases of subcutaneous tumors with hybrid features of schwannoma-perineurioma (one case) and neurofibroma-perineurioma (two cases), which occurred in two women aged 50 and 52 years and one man aged 52. Locations included the scapular area, skin overlying breast and knee area. The tumors were 1.5, 4 and 5 cm in largest diameter. None of the patients had signs of neurofibromatosis. All tumors were surgically removed, and patients remained disease-free for 1 to 4 years. The classification of the lesion into schwannoma-perineurioma and neurofibroma-perineurioma rested on histopathological and immunohistochemical findings. An ultrastructural study was performed in one case of neurofibroma-perineurioma. All cases were studied for mutation of the NF2 gene, and in one case (neurofibroma-perineurioma) a point mutation was detected in exon 15 of the gene.

Three patients with Gardner's syndrome having benign fibrous proliferations in the soft tissues and the oral cavity are presented. Lesions in all three patients were morphologically different. Two excised lesions in Case 1 were histologically identical to nuchal-type fibroma (NTF) and one lesion in this patient was an epidermal cyst. Case 2 had a lesion located in the soft tissues of the shoulder, which was morphologically similar to NTF and, in addition, contained mildly atypical and multinucleated fibroblastic cells. The oral lesion in Case 3 looked like a fibroma and was morphologically different from all fibrous lesions that have ever been described in Gardner's syndrome. The cases in the present report show that the term Gardner's fibroma is just a descriptive name encompassing a spectrum of morphologically different benign fibrous proliferations associated with this syndrome. Therefore, the term Gardner's fibroma should not be used as a specific name for NTF arising in patients with Gardner's syndrome as suggested in the most recent WHO classification of soft tissue and bone tumors.

Twelve cases of spiradenocylindromas, which revealed features of both spiradenoma and cylindroma in the same tumor mass, are presented. Nine female patients had multiple neoplasms occurring mostly on the scalp, and two female and one male patient had a solitary cutaneous lesion. Three of the female patients with multiple cutaneous tumors had a familial history of similar cutaneous neoplasms. In one of the patient's family, the multiple cutaneous tumors were known to occur in multiple family members in four consecutive generations. One patient with multiple cutaneous lesions was known to have associated multiple kidney cysts as confirmed by computed tomography. Histologically, spiradenocylindromas are composed of intermixed areas that are either of typical spiradenoma in appearance or of typical cylindroma appearance. Apocrine and trichoepitheliomatous differentiation seen in two cases in the present series points to spiradenomas, as well as cylindromas, having complex hair follicle (folliculo-sebaceous apocrine) rather than eccrine differentiation. The presence of lymphoid tissue was a histological feature in the present series, which was prominent in all the spiradenomatous parts of the tumors and which was scanty or practically absent in all the cylindromatous parts. The selective presence of lymphocytes in spiradenoma and an absence in cylindroma suggest that spiradenomas have the unique property of attracting lymphocytes. The malignant tumors arising in three patients in the present series had the morphology of a poorly differentiated epithelioid neoplasm. Three patients died of the disease and the other patients were either free of disease or alive with disease 1-30 years on follow up.