Morphologic Diversity of Malignant Neoplasms Arising in Preexisting Spiradenoma, Cylindroma, and Spiradenocylindroma Based on the Study of 24 Cases, Sporadic or Occurring in the Setting of Brooke-Spiegler Syndrome

Abstract

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."

Morphologically low-grade spiradenocarcinoma: a clinicopathologic study of 19 cases with emphasis on outcome and MYB expression

“…They share many morphologic features, and occasionally hybrid tumors with spiradenomatous and cylindromatous components are encountered. 1,2 Although typically observed sporadically as solitary neoplasms, they may rarely be multiple in the setting of the Brooke-Spiegler syndrome. 3,4 Similar to adenoid cystic carcinoma of the breast and salivary glands, the MYB-NFIB gene fusion product, due to a t(6;9)(q22 ∼ 23; p23 ∼ 24) translocation, has recently been demonstrated in a subset of dermal cylindromas, resulting in overexpression of the MYB protein.…”

“…5,[11][12][13] Malignant transformation in eccrine spiradenoma, dermal cylindroma, and cylindroma-spiradenoma hybrid tumors is a rare event with only~150 cases documented in the literature. 1,2,14 The malignant component shows a wide morphological spectrum, ranging from outright invasive adenocarcinoma to more innocuous appearances, reminiscent of basal cell adenocarcinoma of the salivary gland. 2 The tumors have therefore been separated histologically into morphologically low-and high-grade.…”

“…1,2,14 The malignant component shows a wide morphological spectrum, ranging from outright invasive adenocarcinoma to more innocuous appearances, reminiscent of basal cell adenocarcinoma of the salivary gland. 2 The tumors have therefore been separated histologically into morphologically low-and high-grade. 2,14 Their diagnosis depends entirely on adequate sampling and recognition of a pre-existing benign component, most commonly a benign spiradenoma.…”

“…2 The tumors have therefore been separated histologically into morphologically low-and high-grade. 2,14 Their diagnosis depends entirely on adequate sampling and recognition of a pre-existing benign component, most commonly a benign spiradenoma. The morphologically low-grade malignant tumors pose a particular diagnostic challenge owing to their subtle histological changes, characterized by loss of a dual cell population, monotonous cellular growth, increased mitotic activity but only limited cytological atypia.…”

“…The morphologically low-grade malignant tumors pose a particular diagnostic challenge owing to their subtle histological changes, characterized by loss of a dual cell population, monotonous cellular growth, increased mitotic activity but only limited cytological atypia. 2,14 Although traditionally thought of as highgrade skin adnexal carcinomas with aggressive behavior and potential for metastatic spread and associated mortality, more recent studies have suggested a more indolent disease course with favorable outcome, at least for the morphologically low-grade tumors. 1,2,14,15 However, only 18 such cases have been reported with limited available follow-up.…”