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

Am J Surg Pathol. 2009 May;33(5):705-19. doi: 10.1097/PAS.0b013e3181966762.


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."

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / pathology
  • Adenoma / genetics
  • Adenoma / pathology*
  • Adenoma / therapy
  • Adult
  • Aged
  • Aged, 80 and over
  • Australia
  • Carcinoma / genetics
  • Carcinoma / pathology*
  • Carcinoma / therapy
  • Carcinoma, Adenoid Cystic / genetics
  • Carcinoma, Adenoid Cystic / pathology*
  • Carcinoma, Adenoid Cystic / therapy
  • Carcinoma, Skin Appendage / pathology
  • Carcinoma, Squamous Cell / pathology
  • Cell Differentiation
  • Chromosomes, Human, Pair 16
  • Deubiquitinating Enzyme CYLD
  • Europe
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunohistochemistry
  • Male
  • Metaplasia
  • Middle Aged
  • Mutation
  • Neoplasm Invasiveness
  • Neoplasms, Multiple Primary / genetics
  • Neoplasms, Multiple Primary / pathology*
  • Neoplasms, Multiple Primary / therapy
  • Salivary Gland Neoplasms / genetics
  • Salivary Gland Neoplasms / pathology*
  • Salivary Gland Neoplasms / therapy
  • Sarcoma / genetics
  • Sarcoma / pathology*
  • Sarcoma / therapy
  • Soft Tissue Neoplasms / genetics
  • Soft Tissue Neoplasms / pathology*
  • Soft Tissue Neoplasms / therapy
  • South Africa
  • Syndrome
  • Treatment Outcome
  • Tumor Suppressor Proteins / genetics


  • Tumor Suppressor Proteins
  • CYLD protein, human
  • Deubiquitinating Enzyme CYLD