Faculty Bibliography

Clear cell papillary renal cell carcinoma (CCPRCC) is a low-grade, indolent neoplasm with no reported cases of death from disease or metastasis. These lesions can show clinical, morphologic, and immunophenotypic overlap with several aggressive forms of renal cell carcinoma (RCC), including clear cell RCC, translocation RCC, and papillary RCC with cytoplasmic clearing. Given the difference in behavior, it is important to reliably separate these entities. We retrospectively reviewed 47 tumors from 45 patients with morphologic features of CCPRCC. All cases were stained against cytokeratin 7 (CK7), carbonic anhydrase IX (CAIX), and GATA3. Cases inconsistent with CCPRCC were reclassified. In addition, we stained tissue microarrays with 103 typical clear cell RCCs and 62 papillary RCCs, each in triplicate. Twenty-five cases were morphologically and immunophenotypically consistent with CCPRCC; all of them showed diffuse CK7 expression and cup-like reactivity with CAIX. Of these, 19 (76%) showed strong nuclear reactivity for GATA3. Although some non-CCPRCC neoplasms showed at least partial CK7/CAIX coexpression, none were immunopositive for GATA3. All background normal kidneys studied showed GATA3 expression in the distal tubules, collecting ducts, and retention cysts of the distal nephron. On follow-up, none of the patients with CCPRCC had recurrences or metastasis. Sensitivity and specificity for GATA3 staining in the diagnosis of CCPRCC were 76% and 100%, with positive and negative predictive values of 100% and 74%. In conclusion, GATA3 is specific and sensitive for CCPRCC and can be used for accurate distinction from its main mimickers. Coexpression of GATA3 and CK7 in most CCPRCC provides evidence of their origin from distal nephron.

RATIONALE AND OBJECTIVES:To improve resident oral case communication and preparatory skills by providing residents an opportunity to prepare for and conduct a new interdisciplinary Radiology-Pathology (Rad-Path) conference series. MATERIALS AND METHODS:To assess whether conference goals were being achieved, we surveyed trainees and attendings in the radiology and pathology departments. Percentages were examined for each variable. Mann-Whitney U test for ordinal variable significance was applied to determine statistical significance between radiology trainee and attending survey responses. RESULTS:Most surveyed radiology trainees (57.1%) strongly agreed or agreed with: "I wish I felt more comfortable with oral presentations." Sixty-five percent of radiology attendings (34 of 52) either agreed or strongly agreed that the residents should be more comfortable with oral case presentations. Of resident Rad-Path conference presenters, 69% (9 of 13) either agreed or strongly agreed that the conference improved their confidence and/or ability to present case information orally. Of responders who attended at least one Rad-Path conference in person, 83% of residents (19/23) and 61% (17/28) of attendings agreed or strongly agreed that the conference improved their ability to formulate a differential diagnosis. Using the Mann-Whitney U test, no significant difference was found between radiology trainees and attendings' responses. CONCLUSIONS:Our Rad-Path correlation conference was specifically designed and structured to provide residents with focused experience in formal oral case preparation and presentation. We consider our conference a success, with 69% of resident presenters reporting that the Rad-Path conference improved their confidence and/or ability to present case information orally.

Vascular lesions (VLs) of the breast present a diagnostic challenge on breast core biopsy (BCBx). We report on 27 VLs presenting on BCBx. The mean patient age was 60 years, and mean size was 7.5 mm (range, 1.6 to 16 mm). Presentation included palpable mass in 6 (22%), incidental in 6 (22%), and an imaging abnormality in 15 (56%) cases. Imaging impression included hematoma (24%), lymph node (10%), fat necrosis (10%), tortuous vessel (5%), and not provided in 52%. The lesions were classified on the basis of BCBx or BCBx and excision (available in 16 pts) as follows: 1 low-grade angiosarcoma, 8 angiolipomas, 6 capillary hemangiomas, 4 cavernous hemangiomas, 2 hemangiomas (not otherwise specified), 1 papillary endothelial hyperplasia, and 5 perilobular hemangiomas. The angiosarcoma was 9 mm, detected incidentally by magnetic resonance imaging, and showed dissection of stromal collagen, infiltration of glands, high cellularity, moderate cytologic atypia, scant mitotic activity, and Ki-67 reactivity of 10%. Among the 26 benign VLs, worrisome histologic features were noted in 14 on BCBx, including anastomosing vascular channels in 9, moderate cytologic atypia in 4, high cellularity in 2, Ki-67>10% in 2, mitotic activity in 1, and infiltration of glands in 1. Of the 12 VLs without worrisome features, the lesion extended to edge of core in 8, precluding complete evaluation. BCBx of VLs presents diagnostic challenges due to overlapping clinicopathologic and radiologic features with low-grade angiosarcoma. If completeness of removal is documented on BCBx, and cytoarchitectural changes are not worrisome, follow-up could be considered rather than excision. However, only 4 of these cases fulfilled those criteria.

Sinus histiocytosis with massive lymphadenopathy, also known as Rosai-Dorfman disease (RDD), is a rare benign non-Langerhans cell histiocytosis. Twenty-five to forty percent of the cases are extranodal and have been reported in virtually all anatomic locations. In this article, we report a highly unusual case of RDD which presented as multiple pulmonary nodules and associated hilar lymphadenopathy. On resection, extensive obliterative arteritis was noticed. This pathologic presentation of RDD has not been reported before in the English literature. Accurate recognition of this entity is crucial to prevent unnecessary aggressive treatment.

OBJECTIVES/OBJECTIVE:To describe the radiologic and clinicopathologic features of extranodal Rosai-Dorfman disease (RDD) in our patient population. METHODS:Via a data mining engine, we evaluated 13 cases of extranodal RDD in 10 patients treated at our institution from 2000 to 2014. RESULTS:There was a marked female predominance (90%) in our series. The most common clinical presentation was a palpable, painless mass, which often simulated a neoplasm. Only two cases occurred in children. Multicentric and recurrent disease were uncommon. Histologically, all cases showed large histiocytes with emperipolesis in a mixed inflammatory background, with areas of dense, storiform collagen fibrosis. Positive S-100 and CD68 with negative CD1a in histiocytes are characteristic. CONCLUSIONS:Extranodal RDD is rare and its manifestations varied. It may constitute a clinical and pathologic diagnostic challenge. Clinical suspicion and recognition of its histologic features are necessary for correct diagnosis and avoiding unnecessary treatment. Resection is curative in most cases.

Onboarding is a system frequently used in the corporate world as a means of orienting incoming employees to their duties and inculcating the workplace values. The program aims to facilitate transition into new work roles and improve employee retention rates. At Montefiore, we have instituted an onboarding curriculum that is given to new anatomic and clinical pathology residents about a month prior to the start of residency. The program includes an introductory video series of basic histology and a series of anatomic and clinical case studies illustrating basic laboratory principles. This didactic content is tagged to learning objectives and short self-assessment modules. In addition, content related to the work ethos at Montefiore and the role of the core competencies and milestones in residency education are included. Finally, a broader component of the onboarding gives the incoming residents a social welcome to our area, including key information about living in the area surrounding Montefiore. The program has been well received by our residents for whom the content has helped to boost confidence when starting. We feel that the program is helpful in ensuring that all incoming residents start having received the same baseline didactic content. Transmitting this didactic content via onboarding allows our residents to begin the work of learning pathology immediately, rather than spending the first weeks of residency covering remedial content such as basic histology. Such a program may be useful to other pathology residencies, most of whom have residents from a range of backgrounds and whose prior exposure to pathology may be limited.

AIM/OBJECTIVE:Peripheral blood-derived endothelial cells (pBD-ECs) are an attractive tool for cell therapies and tissue engineering, but have been limited by their low isolation yield. We increase pBD-EC yield via administration of the chemokine receptor type 4 antagonist AMD3100, as well as via a diluted whole blood incubation (DWBI). MATERIALS & METHODS/METHODS:Porcine pBD-ECs were isolated using AMD3100 and DWBI and tested for EC markers, acetylated LDL uptake, growth kinetics, metabolic activity, flow-mediated nitric oxide production and seeded onto titanium tubes implanted into vessels of pigs. RESULTS:DWBI increased the yield of porcine pBD-ECs 6.6-fold, and AMD3100 increased the yield 4.5-fold. AMD3100-mobilized ECs were phenotypically indistinguishable from nonmobilized ECs. In porcine implants, the cells expressed endothelial nitric oxide synthase, reduced thrombin-antithrombin complex systemically and prevented thrombosis. CONCLUSION/CONCLUSIONS:Administration of AMD3100 and the DWBI method both increase pBD-EC yield.

Heart failure is a common complication of doxorubicin (DOX) therapy. Previous studies have shown that DOX adversely impacts cardiac energy metabolism, and the ensuing energy deficiencies antedate clinical manifestations of cardiac toxicity. Brief exposure of cultured cardiomyocytes to DOX significantly decreases creatine transport, which is the cell's sole source of creatine. We present the results of a study performed to determine if physiological creatine supplementation (5 mmol/L) could protect cardiomyocytes in culture from cellular injury resulting from exposure to therapeutic levels of DOX. Creatine supplementation significantly decreased cytotoxicity, apoptosis, and reactive oxygen species production caused by DOX. The protective effect was specific to creatine and depended on its transport into the cell.