Lipid-rich variant of pancreatic endocrine neoplasms.

Department of Pathology, Harper Hospital and Karmanos Cancer Institute, Wayne State University, Detroit, MI 48201, USA.
American Journal of Surgical Pathology (Impact Factor: 4.59). 03/2006; 30(2):194-200. DOI: 10.1097/
Source: PubMed

ABSTRACT Most pancreatic endocrine neoplasms (PENs) show characteristic and well-recognized endocrine morphology; however, a lipid-rich pattern, which can present a diagnostic problem in biopsies, has been reported, mostly as individual cases. Some have been included in descriptions of the rare clear-cell variant associated with von Hippel-Lindau (VHL) syndrome. The histogenesis, clinicopathologic characteristics, and significance of this lipid-rich pattern have not been unraveled. In this study, 11 PENs exhibiting foamy, microvesicular cytoplasm were analyzed. In some cases, the nuclei were distorted by the vesicles, and the usual endocrine chromatin pattern was not evident. The growth pattern was relatively diffuse, with vague compartmentalization of the cells by a delicate vasculature; prominent nesting was noted in only 4 cases. Pathology reports indicated substantial diagnostic challenge in these cases; on biopsies, 1 case was originally diagnosed as adrenal cortical carcinoma, another as renal cell carcinoma, a third as solid-pseudopapillary tumor, and a fourth had a fine needle aspiration cytologic diagnosis of adenocarcinoma. All cases were chromogranin and synaptophysin positive. Electron microscopy in 3 cases confirmed the cytoplasmic vesicles to be lipid vacuoles. Neurosecretory granules were also evident. Clinically, as in conventional PENs, there appeared to be two distinct subsets: Two cases were familial or functional/syndromic (1 with VHL and the other with MEN-1 and glucagonoma syndrome) and occurred in younger adults (ages 41 and 47 years); the majority (n = 9) were nonfunctional/nonsyndromic and nonfamilial. The latter group was mostly represented by elderly males (mean age: 65 vs. 58 years in conventional sporadic PENs). Immunohistochemically, markers implicated in VHL-associated neoplasia, including HIF-1alpha, inhibin, and Melan-A (in clear-cell PENs) and MUC6 (in serous cystadenomas) were mostly negative in lipid-rich PENs (1 of 10, 1 of 10, 0 of 10 and 0 of 10, respectively). In conclusion, the lipid-rich pattern, reminiscent of adrenal cortical cells, represents a distinct subset of PENs. It presents a diagnostic challenge for surgical pathologists, especially in biopsies. EM supports the name lipid-rich for this variant. The findings suggest that the pathogenesis of lipid-rich tumors may be different from the VHL-associated clear-cell variants of PENs.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Solid-pseudopapillary neoplasm (SPN) of the pancreas is a rare neoplasm predominantly reported in young women. It classically presents as a large tumor with cystic and solid components. The major differential diagnosis includes pancreatic neuroendocrine tumor (PanNET). This study presents our experience with this tumor with emphasis on the morphologic features of the clear cell variant of SPN. Fifteen histologically confirmed SPN were identified in our files. Endoscopic ultrasound-guided fine needle aspirations (EUS-guided FNA) were performed in 8/15 cases. Patients' demographics, cytohistologic correlation and tumor characteristics were evaluated. Eleven of the 15 subjects were female and four were male with an age range of 17-73 years. Twelve SPN were located in the pancreatic body/tail, and three in the head. Tumor size ranged from 1.5 to 8.5 cm and 11 were solid. Of the eight EUS-guided FNA, four were diagnosed as SPN, two as SPN vs. PanNET, one as malignant with signet ring features, and one was nondiagnostic. Immunohistochemistry was performed on six/eight FNA cell blocks and 13/15 surgical specimens. Two of the 15 cases were classified as clear cell variants of SPN. Our study shows that SPN may occur in males and older adults, and present as a small or solid tumor. The clear cell variant of SPN, characterized by vacuolated cytoplasm and signet cell morphology, may pose a diagnostic challenge on FNA. Awareness of the wide spectrum of SPN clinical presentations, the morphology of its clear cell variant and the appropriate use of ancillary immunohistochemistry can prevent diagnostic errors. Diagn. Cytopathol. 2013. © 2013 Wiley Periodicals, Inc.
    Diagnostic Cytopathology 04/2013; 41(10). DOI:10.1002/dc.22989 · 1.52 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: von Hippel-Lindau (VHL) disease is a hereditary autosomal dominant disorder associated with deletions or mutations in the VHL tumor suppressor gene. Characteristically, up to 60 % of neuroendocrine tumors (NETs) associated with VHL disease display a spectrum of clear cell morphology including multivacuolated lipid-rich cell change. Unlike neurofibromatosis type 1 and multiple endocrine neoplasia type 1 syndromes, ampullary NETs have not been described in association with VHL disease. In this report, we discuss the features of an incidental ampullary clear cell NET occurring in a patient with pancreatic VHL disease including multiple pancreatic NETs. The ampullary lesion consisted of epithelial cells resembling lipoblasts or signet ring cells. In our case, all NETs showing clear cell change were positive for inhibin. While the underlying mechanism of this finding is largely unknown, it is of note that positivity for inhibin has not been observed in clear cell NETs associated with multiple endocrine neoplasia type 1 syndrome. Our case proves that NETs can develop in the ampullary region in patients with VHL; clear cell change can occur in these lesions and can mimic signet ring cell carcinoma. This issue is of clinical significance especially in small biopsy samples; thus, positivity for keratin alone should not be taken as evidence of an adenocarcinoma. Moreover, demonstration of inhibin expression in a NET with clear cell change along with other clinical stigmata should alert the diagnostician to the possibility of VHL disease. However, further larger series examining inhibin expression in both syndrome-related and sporadic clear cell NETs are needed to confirm our findings.
    Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 08/2013; 463(4). DOI:10.1007/s00428-013-1465-6 · 2.56 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Pancreatic endocrine tumor (PET) is an uncommon neoplasm of the pancreas with distinct cytomorphologic features. Lipid-rich PET, a rare variant, histologically deviates from that of a conventional PET. There is only one case report of the cytologic features of this rare entity in the literature. We report two cases of lipid-rich PETs diagnosed by endoscopic ultrasound-guided FNA biopsy. Case 1 showed large aggregates, small clusters, and single cells with plasmacytoid appearance, small uniform nuclei, coarse chromatin, and prominent nucleoli. Abundant distinct small cytoplasmic vacuoles were present in almost all tumor cells and the background was clean. Case 2 showed flat cohesive sheets of medium-sized uniform cells with indistinct plasmacytoid appearance, uniform nuclei, fine and evenly distributed chromatin, and inconspicuous nucleoli. Distinct small cytoplasmic vacuoles were seen only focally. Immunohistochemical stains in cell blocks of both cases confirmed the diagnosis of PET. Lipid-rich PET may be misinterpreted on cytology specimens if the pathologist is not aware of this rare entity since it mimics clear cell carcinoma of the kidney, adrenal cortical neoplasm, or adenocarcinoma of the pancreas. Diagn. Cytopathol. 2013. © 2013 Wiley Periodicals, Inc.
    Diagnostic Cytopathology 04/2014; 42(4). DOI:10.1002/dc.23009 · 1.52 Impact Factor

Full-text (2 Sources)

Available from
Aug 18, 2014