title: 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."
authors.affiliation: Sikl's Department of Pathology, Charles University Medical Faculty Hospital, Pilsen, Czech Republic. kazakov@medima.cz
authors.forename: Dmitry V
authors.initials: DV
authors.lastname: Kazakov
authors.forename: Bernhard
authors.initials: B
authors.lastname: Zelger
authors.forename: Arno
authors.initials: A
authors.lastname: Rütten
authors.forename: Marina
authors.initials: M
authors.lastname: Vazmitel
authors.forename: Dominic V
authors.initials: DV
authors.lastname: Spagnolo
authors.forename: Denisa
authors.initials: D
authors.lastname: Kacerovska
authors.forename: Tomas
authors.initials: T
authors.lastname: Vanecek
authors.forename: Petr
authors.initials: P
authors.lastname: Grossmann
authors.forename: Radek
authors.initials: R
authors.lastname: Sima
authors.forename: Wayne
authors.initials: W
authors.lastname: Grayson
authors.forename: Eduardo
authors.initials: E
authors.lastname: Calonje
authors.forename: Jan
authors.initials: J
authors.lastname: Koren
authors.forename: Petr
authors.initials: P
authors.lastname: Mukensnabl
authors.forename: Dusan
authors.initials: D
authors.lastname: Danis
authors.forename: Michal
authors.initials: M
authors.lastname: Michal
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology; D000236:Adenoma / Q000235:genetics / Q000473:pathology* / Q000628:therapy; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001315:Australia; D002277:Carcinoma / Q000235:genetics / Q000473:pathology* / Q000628:therapy; D003528:Carcinoma, Adenoid Cystic / Q000235:genetics / Q000473:pathology* / Q000628:therapy; D018280:Carcinoma, Skin Appendage / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000473:pathology; D002454:Cell Differentiation; D002885:Chromosomes, Human, Pair 16; D000074749:Deubiquitinating Enzyme CYLD; D005060:Europe; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008679:Metaplasia; D008875:Middle Aged; D009154:Mutation; D009361:Neoplasm Invasiveness; D009378:Neoplasms, Multiple Primary / Q000235:genetics / Q000473:pathology* / Q000628:therapy; D012468:Salivary Gland Neoplasms / Q000235:genetics / Q000473:pathology* / Q000628:therapy; D012509:Sarcoma / Q000235:genetics / Q000473:pathology* / Q000628:therapy; D012983:Soft Tissue Neoplasms / Q000235:genetics / Q000473:pathology* / Q000628:therapy; D013019:South Africa; D013577:Syndrome; D016896:Treatment Outcome; D025521:Tumor Suppressor Proteins / Q000235:genetics
chemical_list: D025521:Tumor Suppressor Proteins; C409984:CYLD protein, human; D000074749:Deubiquitinating Enzyme CYLD