Although many of the common manifestations of Von Hippel-Lindau (VHL) disease are relatively well known, there is one particular entity which is quite rare, but which appears to show a specific predilection for VHL patients. This entity is clear cell neuroendocrine tumor (NET). It is a difficult diagnosis to make due to its cytomorphologic similarities to other entities, such as metastatic clear cell renal cell carcinoma and paraganglioma, amongst others. These tumors, however, are characteristically positive for neuroendocrine markers such as synaptophysin and chromogranin, as well as cytokeratins. Emerging evidence also suggests that clear cell NETs in VHL patients are specifically positive for inhibin, when compared to their counterparts in non-VHL patients, which may assist in the diagnosis in as yet undiagnosed patients with VHL disease. Herein, we present two cases of inhibin-positive clear cell NETs, one in a VHL patient, and the other in a non-VHL patient. These cases propose a potential warning to those relying on inhibin positivity to incite an expedition down a rabbit hole for a diagnosis of VHL. Diagn. Cytopathol. 2017;45:757-760. © 2017 Wiley Periodicals, Inc.

A 36-year-old woman with past medical history of neurofibromatosis-1 (NF1) presented to the emergency department with left breast pain and rapid enlargement her left breast. She noted history of a palpable left breast mass for the past 13 years. Physical examination revealed a firm, nonmobile mass that encompassed a majority of the breast with the left approximately five times the size of the right (Figure 1). She was referred for clinical evaluation and imaging. The

BackgroundErdheim Chester disease (ECD) is a rare, non-Langerhans cell histiocytosis characterized by widespread tissue infiltration by CD68-positive, CD1a-negative foamy histiocytes. ECD can be difficult to identify, and diagnosis relies on the presence of histiocytes with certain histologic and immunophenotypic features in an appropriate clinical and radiologic setting. Clinical signs and symptoms are variable depending on which organ systems are involved. Most patients have at least skeletal involvement with bone pain as well as fatigue. Other common manifestations include diabetes insipidus, cardiac, periaortic, or retro-orbital infiltration/fibrosis, kidney impairment, xanthelasmas, among others.Case presentationHerein, we describe a case of BRAF-mutation positive ECD in a patient with Burkitt lymphoma, and we review recent literature.ConclusionUnderlying BRAF and other MAPK pathway mutations are identified in approximately 50% of cases of ECD, which aids in diagnosis as well as enables novel targeted treatments. ECD patients have an increased risk of myeloid neoplasms; however, unlike other histiocytoses, an association with lymphoproliferative disorders has not been recognized.

When evaluating a Papanicolaou (Pap) smear, the cytology of the squamous epithelial cells is of utmost importance. This is what cytopathologists use to render a diagnosis, ranging from normal to atypical squamous cells of undetermined significance (ASCUS) to high grade squamous intraepithelial lesions, or even squamous cell carcinoma. However, occasionally the pathologist will run into microscopic noncellular material as in our case, such as corpora amylacea on the slides, or even uncommon viral inclusions such as Molluscum contagiosum (MCV). When these less common entities make their way on to a cervical Pap smear, it is important not only to correctly recognize them, but to understand their clinical implications as well. Diagn. Cytopathol. 2017;45:179-181. © 2016 Wiley Periodicals, Inc.

Desmoplastic small round cell tumor (DSRCT) is an aggressive pediatric round cell sarcoma containing a characteristic EWSR1-WT1 gene fusion. In the absence of genetic data, distinguishing DSRCT from other small round cell tumors of childhood can be problematic due to overlapping histologic and immunohistochemical features. We studied the utility of immunohistochemistry with antibodies targeting both the amino-terminal and carboxy-terminal regions of the Wilms tumor-1 (WT1) protein in differentiating these groups of tumors. The study cohort included 33 cases of genetically confirmed pediatric round cell tumors (10 DSRCTs, 12 Wilms tumors, 10 Ewing sarcomas, and 1 CIC-rearranged sarcoma). Immunoreactivities and immunolocalization of both the WT1 amino-terminus and carboxy-terminus were scored and documented. All DSRCTs displayed selective reactivity for only the WT1 carboxy-terminus (10/10), while dual immunoreactivity for both the WT1 carboxy-terminus (12/12) and amino-terminus antibodies (12/12) were characteristic of Wilms tumors. CIC-rearranged sarcoma showed variable WT1 nuclear immunopositivity (1/1, 1/1) and Ewing sarcomas were consistently WT1-negative for both the WT1 amino-terminus (0/10) and carboxy-terminus (0/10). Dual WT1 amino-terminus and carboxy-terminus immunohistochemistry remains a helpful diagnostic tool in discriminating intraabdominal small round cell tumors, which serves as an adjunct to the genetic information in preventing misdiagnosis.