Comparing Accuracy of Helicobacter pylori Identification Using Traditional Hematoxylin and Eosin-Stained Glass Slides With Digital Whole Slide Imaging.

With advancements in the field of digital pathology, there has been a growing need to compare the diagnostic abilities of pathologists using digitized whole slide images against those when using traditional hematoxylin and eosin (H&E)-stained glass slides for primary diagnosis. One of the most common specimens received in pathology practices is an endoscopic gastric biopsy with a request to rule out Helicobacter pylori (H. pylori) infection. The current standard of care is the identification of the organisms on H&E-stained slides. Immunohistochemical or histochemical stains are used selectively. However, due to their small size (2-4 µm in length by 0.5-1 µm in width), visualization of the organisms can present a diagnostic challenge. The goal of the study was to compare the ability of pathologists to identify H. pylori on H&E slides using a digital platform against the gold standard of H&E glass slides using routine light microscopy. Diagnostic accuracy rates using glass slides vs digital slides were 81% vs 72% (P = .0142) based on H&E slides alone. When H. pylori immunohistochemical slides were provided, the diagnostic accuracy was significantly improved to comparable rates (96% glass vs 99% digital, P = 0.2199). Furthermore, differences in practice settings (academic/subspecialized vs community/general) and the duration of sign-out experience did not significantly impact the accuracy of detecting H. pylori on digital slides. We concluded that digital whole slide images, although amenable in different practice settings and teaching environments, does present some shortcomings in accuracy and precision, especially in certain circumstances and thus is not yet fully capable of completely replacing glass slide review for identification of H. pylori. We specifically recommend reviewing glass slides and/or performing ancillary stains, especially when there is a discrepancy between the degree of inflammation and the presence of microorganisms on digital images.

Isolated arterial mucoid intimal thickening lesion in early post-transplant kidney allograft biopsies.

INTRODUCTION: Thrombotic microangiopathy (TMA) on kidney biopsy shows a variable combination of features: arterial mucoid intimal thickening, acellular closure of glomerular capillary loops, fragmented red blood cells, fibrin thrombi, and arterial fibrinoid necrosis. However, some early post-transplant kidney biopsies show only arterial mucoid intimal thickening. We aimed to elucidate the importance of this finding. METHODS: We identified 19 biopsies showing isolated arterial mucoid intimal thickening and compared them with 22 bona fide TMA biopsies identified based on the pathological findings (excluding rejection) (2011-2020). Additionally, delayed graft function (DGF) (n = 237), and no DGF (control, n = 1314) groups were included for survival analysis. RESULTS: Seven of 19 cases with isolated arterial mucoid intimal thickening showed peripheral blood schistocytes but no other systemic features of TMA. Eight patients underwent adjustments in maintenance immunosuppression (mainly calcineurin inhibitors). None of the cases progressed to full-blown TMA on consecutive biopsies. The overall and death-censored graft survival rates in this group were comparable to the DGF group, but significantly better than the TMA group (P = .005 and .04, respectively). CONCLUSIONS: Isolated arterial mucoid intimal thickening in early post-transplant biopsies may be an early/mild form of TMA, probably requiring adjustment in immunosuppressive regimen. Careful exclusion of known causes of TMA, and donor-derived arterial injury are important.

Wnt Family Member 9b (Wnt9b) Is a Sensitive and Specific Marker for Triple-negative Breast Carcinoma Including Metaplastic Carcinoma.

Wnt9b was recently identified as a highly sensitive and specific marker for breast carcinomas. Due to the limited number of triple-negative breast carcinomas (TNBCs) in previous study, we further explored Wnt9b's utility in breast carcinoma, especially in TNBCs including metaplastic carcinomas. We systematically evaluated Wnt9b expression on tissue microarrays (TMAs) from 413 breast carcinomas, 208 urothelial carcinomas, 102 endometrial carcinomas, 109 cholangiocarcinomas, 192 ovarian carcinomas, 48 lung adenocarcinomas, 69 colorectal adenocarcinomas, and 78 melanomas, and whole tissue section (WTS) from 20 human epidermal growth factor receptor 2-positive, 34 nonmetaplastic TNBCs, and 67 invasive metaplastic carcinomas. The results showed Wnt9b was highly expressed in breast carcinomas (91% on TMA and 98% on WTS) and in nonmetaplastic TNBCs (91% on TMA and 97% on WTS), but almost completely negative in other tested tumor types. Wnt9b was also highly expressed in metaplastic carcinomas (80%), significantly higher than GATA3 (56%) and SOX10 (48%), but slightly lower than TRPS1 (90%). In summary, our results demonstrate that Wnt9b is a highly sensitive marker for breast carcinomas, including TNBCs and metaplastic carcinomas. Further, we compared its utility with other breast markers including TRPS1, GATA3, and SOX10 in metaplastic carcinomas.

TRPS1 Expression in Breast Carcinomas: Focusing on Metaplastic Breast Carcinomas.

TRPS1 has been recently demonstrated as a highly sensitive and specific marker for breast carcinomas. To further explore TRPS1's utility in breast carcinoma, we systematically evaluated TRPS1 expression on tissue microarrays from 160 estrogen receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-positive, 94 ER-/HER2+, 117 triple-negative breast carcinomas, and 618 other primary carcinomas (cholangiocarcinoma, endometrial, colorectal, and hepatocellular carcinomas), and whole tissue sections from 64 HER2+, 76 triple-negative, and 67 metaplastic breast carcinomas. The results showed TRPS1 was highly expressed in breast carcinomas (100% of HER2+ and 97.4% of triple negative on whole tissue sections), but almost completely negative in other tested tumor types. TRPS1 was also highly expressed in metaplastic carcinoma (91%), significantly higher than GATA3 (55.2%). The different expression between TRPS1 and GATA3 was most prominent in chondroid/mesenchymal subtypes (100% vs. 36.4%), followed by spindle cell carcinoma (66.7% vs. 44.4%). In addition, TRPS1 was expressed in normal breast ductal epithelial cells with less staining than in carcinoma cells, and TRPS1 showed aberrant membranous staining in HER2+ breast carcinomas that suggests a potential cross-reactivity with HER2 protein.

The hospital autopsy: the importance in keeping autopsy an option.

Autopsy has been one of the most powerful diagnostic tools in medicine for over a century. Despite its importance in establishing cause of death and elucidating pathophysiology of disease, rates of hospital autopsies continue to decline. In this study we aim to determine if physicians believe autopsies are essential to patient care through discussion of autopsy with families. At the same time, we analyzed whether families are more willing to consent to autopsy if physicians are involved in autopsy discussion at the time of death, and what may be the reasons for not wanting an autopsy. Our results showed a doubling in autopsy consent when autopsy was discussed by the physician. Additionally, the biggest reason for families not consenting to autopsy was because they believed they already knew what caused death. The emergence of Coronavirus 2019 (COVID-19) has re-established the value of autopsy, as seen by increased autopsy rates in the past year. This study demonstrates that physician conversation with families on autopsy leads to an increased chance of autopsy consent.

Intraneural Nodular Fasciitis of the Femoral Nerve with A Unique CTNNB1::USP6 Gene Fusion: Apropos of a Case and Review of Literature.

Nodular fasciitis (NF) is a benign proliferation of fibroblasts and myofibroblasts occurring most commonly in the upper extremities that can mimic a variety of mesenchymal tumors including sarcoma. Although reported in almost all anatomic locations, only 7 cases of intraneural nodular fasciitis have been reported in English literature. The CTNNB1::USP6 gene fusion has not been previously reported in intraneural nodular fasciitis, although it has been reported in three entities including aneurysmal bone cyst, nodular fasciitis, and intravascular fasciitis. We report a case of a 29-year-old female with a 6-month history of left leg weakness, myalgia, and paresthesia of the left foot prompting a clinical diagnosis of a peripheral nerve sheath tumor. Surgical resection was performed, and histologic sections revealed a circumscribed lesion composed of banal spindle cells with variable interstitial collagen and occasional mitotic figures. By immunohistochemistry, the lesional cells were positive for smooth muscle actin, smooth muscle heavy chain myosin, p16, and H-caldesmon and negative for desmin, S-100, SOX10, HMB45, CD34, and beta-catenin. Fluorescence in Situ Hybridization for USP6 gene rearrangement was positive and consistent with the diagnosis of nodular fasciitis. Next-generation sequencing uncovered the presence of a CTNNB1::USP6 gene fusion involving CTNNB1 gene in exon 1 at the genomic position chr3:41241161 and the USP6 gene in exon 1 at the genomic position chr17:5033231. This gene fusion was confirmed by Sanger sequencing. Herein, we report a case that underscores the rare incidence of intraneural nodular fasciitis and highlights the pitfalls associated with the clinical differential diagnoses of intraneural tumors.

TRPS1, GATA3, and SOX10 expression in triple-negative breast carcinoma.

A diagnostic dilemma can be encountered when primary triple-negative breast carcinoma (TNBC) without an in situ component or metastatic TNBCs lose the currently used organ-specific marker such as GATA3, raising concerns about metastatic carcinoma from other sites. In the current study, we compared the newly identified breast marker TRPS1 with currently used breast markers GATA3 and SOX10 in whole-tissue sections from 315 cases of various subtypes of TNBC. TRPS1 was highly expressed in 100% of triple-negative primary and metastatic invasive lobular carcinomas, 99% of triple-negative primary and metastatic invasive breast carcinoma of no special type (IBC-NST), and 95% of metaplastic breast carcinomas. In contrast, GATA3 and SOX10 were expressed in 94% and 0% of invasive lobular carcinomas, 63% and 74% of IBC-NST, and 50% and 49% of metaplastic breast carcinomas, respectively. For special-type TNBCs, both TRPS1 and GATA3 were negative in acinic cell carcinomas, most cribriform adenoid cystic carcinomas, and neuroendocrine carcinomas, but positive in secretory carcinomas. Triple-negative apocrine carcinoma was the only subtype of TNBC with positive GATA3 but negative TRPS1. These data indicate that TRPS1 is a highly sensitive marker for TNBCs with positivity not only in GATA3/SOX10-positive TNBCs but also in almost all GATA3/SOX10-negative TNBCs.

The hospital autopsy: the importance in keeping autopsy an option

Autopsy has been one of the most powerful diagnostic tools in medicine for over a century. Despite its importance in establishing cause of death and elucidating pathophysiology of disease, rates of hospital autopsies continue to decline. In this study we aim to determine if physicians believe autopsies are essential to patient care through discussion of autopsy with families. At the same time, we analyzed whether families are more willing to consent to autopsy if physicians are involved in autopsy discussion at the time of death, and what may be the reasons for not wanting an autopsy. Our results showed a doubling in autopsy consent when autopsy was discussed by the physician. Additionally, the biggest reason for families not consenting to autopsy was because they believed they already knew what caused death. The emergence of Coronavirus 2019 (COVID-19) has re-established the value of autopsy, as seen by increased autopsy rates in the past year. This study demonstrates that physician conversation with families on autopsy leads to an increased chance of autopsy consent.