Browsing by Author "Hwang, Michael"

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    Endocrine cell micronests in an ovarian mucinous borderline tumor: a potential diagnostic pitfall for microinvasion
    (BMC, 2022-04-14) Collins, Katrina; Segura, Sheila; Hwang, Michael; Pathology and Laboratory Medicine, School of Medicine
    The occurrence of endocrine cell micronests in ovarian tumors is rarely reported. To our knowledge, there are only three prior cases reported to date: one occurring in an ovarian mucinous cystadenoma, one in an ovarian mucinous cystadenofibroma, and another in an ovarian mucinous carcinoma with a predominant borderline component. This is a 27-year-old woman that presented with a one-month history of abdominal pain and fullness. Imaging studies revealed a large multiloculated cystic and solid mass measuring 23 cm occupying the majority of the pelvis and abdomen concerning for a primary ovarian malignancy. The patient underwent a right salpingo-oophorectomy with appendectomy. Histologic sections from the ovary showed a multiloculated, cystic and focally solid mass lined by gastrointestinal-type mucinous epithelium with variable degrees of proliferation accounting for greater than 10% of the tumor. In addition to the mucinous epithelial component, there were several foci of bland, monotonous epithelioid cells arranged in solid nests with focal tubular/acinar formation within the fibrous septa and mucinous epithelium. Immunohistochemical studies showed that these cells were positive for cytokeratin, EMA, and synaptophysin, while negative for inhibin. The Ki-67 proliferation index was low (<1%). The presence of endocrine cell nests associated with an ovarian mucinous neoplasm is a rare phenomenon. Whether this represents preservation of endocrine cells in the context of epithelial degeneration or an independent neoplastic component is unclear. Progression related to this endocrine cell proliferation is unlikely and the recognition of this phenomenon holds more diagnostic value than prognostic significance, as it could be confused with microinvasion or sex cord stromal elements.
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    A generative adversarial approach to facilitate archival-quality histopathologic diagnoses from frozen tissue sections
    (Elsevier, 2022) Falahkheirkhah, Kianoush; Guo, Tao; Hwang, Michael; Tamboli, Pheroze; Wood, Christopher G.; Karam, Jose A.; Sircar, Kanishka; Bhargava, Rohit; Pathology and Laboratory Medicine, School of Medicine
    In clinical diagnostics and research involving histopathology, formalin-fixed paraffin-embedded (FFPE) tissue is almost universally favored for its superb image quality. However, tissue processing time (>24 h) can slow decision-making. In contrast, fresh frozen (FF) processing (<1 h) can yield rapid information but diagnostic accuracy is suboptimal due to lack of clearing, morphologic deformation and more frequent artifacts. Here, we bridge this gap using artificial intelligence. We synthesize FFPE-like images ("virtual FFPE") from FF images using a generative adversarial network (GAN) from 98 paired kidney samples derived from 40 patients. Five board-certified pathologists evaluated the results in a blinded test. Image quality of the virtual FFPE data was assessed to be high and showed a close resemblance to real FFPE images. Clinical assessments of disease on the virtual FFPE images showed a higher inter-observer agreement compared to FF images. The nearly instantaneously generated virtual FFPE images can not only reduce time to information but can facilitate more precise diagnosis from routine FF images without extraneous costs and effort.
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    Merlin immunohistochemistry is useful in diagnosis of tumours within the spectrum of biphasic hyalinizing psammomatous renal cell carcinoma
    (Wiley, 2022-11) Collins, Katrina; Hwang, Michael; Antic, Tatjana; Paintal, Ajit; Argani, Pedram; Matoso, Andres; Gopinath, Arun; Baskovich, Brett; Mehra, Rohit; Williamson, Sean R.; Idrees, Muhammad T.; Barletta, Justine A.; Anderson, William J.; Hirsch, Michelle S.; Hornick , Jason L.; Acosta, Andres M.; Pathology and Laboratory Medicine, School of Medicine
    Aims: Biphasic hyalinizing psammomatous (BHP) renal cell carcinoma (RCC) is a newly described emerging entity within the spectrum of papillary RCC in the WHO 2022 classification. Molecular analyses have discovered that BHP RCC consistently harbour somatic mutations in the neurofibromin 2 (NF2) gene. The NF2 gene product, merlin, is known to primarily function as a tumour suppressor. Merlin protein loss correlates closely with the presence of NF2 mutations in benign and malignant tumours arising in different sites. In the present study we explored the role of merlin immunohistochemistry (IHC) in tumours within the spectrum of BHP RCC to determine the diagnostic utility of this marker. Materials and methods: We performed merlin IHC in 13 BHP RCC, 18 papillary RCC, 10 TFE3-translocation RCC, 15 TFEB-altered RCC (including 13 TFEB-rearranged and 2 TFEB-amplified), and 10 mucinous tubular and spindle cell carcinomas of unknown mutational status. Results: Unequivocal loss of merlin expression in >90% of the tumour cells was observed in 12/13 BHP-RCC (92%), with the remaining tumour demonstrating weak focal cytoplasmic expression in ~10% of the tumour. In contrast, merlin was diffusely or multifocally expressed in all papillary RCC, TFE3-translocation RCC, and TFEB-altered RCC, as well as in 70% of mucinous tubular and spindle carcinomas. Conclusions: In this study, merlin IHC was ~92% sensitive and ~94% specific for BHP RCC. These data suggest that merlin IHC is a reliable surrogate marker for the presence of underlying NF2 gene inactivation, being diagnostically useful to identify BHP RCC.
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    Renal Replacement Lipomatosis Presenting in the Setting of Ureteral Stricture with Absence of Renal Calculus Disease
    (Hindawi, 2021-10-23) Collins, Katrina; Brocken, Eric; Warmke, Laura M.; Tirkes, Temel; Hwang, Michael; Pathology and Laboratory Medicine, School of Medicine
    Renal replacement lipomatosis of the kidney is a rare, benign entity in which extensive fibrofatty proliferation of the renal sinus is associated with marked atrophy of the renal parenchyma. It is often associated with calculi or long-standing inflammation. This entity may be confused with a fatty neoplasm of the kidney. A 51-year-old woman with a past medical history of pancreas transplant for type 1 diabetes subsequently developed ureteral stricture. This was initially managed by a nephrostomy tube and nephroureterostomy stenting with periodic exchanges to help restore urine flow; however, the renal function of the kidney progressively declined with recurrent and complicated urinary tract infections. She presented for kidney transplant with right native nephrectomy. Gross examination of the right kidney revealed a 12.8 cm renal sinus lipomatous mass replacing much of the kidney. Microscopically, the mass consisted of mature adipose tissue with fibrous septae and occasional thick-walled vessels with prominent smooth muscle bundles. A rare atypical stromal cell was present, otherwise no significant cytologic atypia or lipoblasts were identified. After excluding fat-predominant angiomyolipoma and well-differentiated liposarcoma, a diagnosis of renal replacement lipomatosis was made. Renal replacement lipomatosis is a benign condition typically associated with a nonfunctioning or poorly functioning kidney often linked to renal calculus disease or chronic renal infection. The presentation in our case was atypical given an absence of associated renal calculus disease. This case is intended to increase awareness of this less commonly encountered entity as it may be confused with a fatty neoplasm of the kidney, some with malignant potential.