OBJECTIVES:We sought to investigate the diagnostic value of lymphocyte enhancer factor 1 (LEF1) expression in aggressive B-cell lymphomas (BCL) with MYC gene rearrangement (MYC-R). METHODS:Sixty-seven cases of BCL were studied and included Burkitt lymphoma (BL) (23 cases); diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS) with MYC-R (13 cases); and DLBCL/high-grade B-cell lymphoma with MYC, BCL2, and/or BCL6 rearrangements (double-hit [DH] or triple-hit [TH], 17 cases). Random DLBCL-NOS (14 cases) without MYC-R was recruited as a control group. By immunohistochemical stains, 3 patterns of LEF1 staining were recorded as pattern 0 (negative), pattern 1 (weak and heterogeneous staining, <80%), and pattern 2 (moderate/strong and uniform staining, ≥80%). RESULTS:Pattern 1 can be seen in all BCLs with MYC-R included in this study and more commonly seen in DLBCL without MYC-R (8/14 cases). Pattern 2 is characteristic (positive predictive value = 86%) for Epstein-Barr virus (EBV)-negative BL, while pattern 0 was seen in 22 (76%) of 29 cases of DLBCL-MYC-R/DH/TH (P < .001). Seven of 8 EBV-positive BL cases showed pattern 0, which was completely opposite to the common pattern 2 in EBV-negative BL (12/15 cases). Pattern 2 was not detected in all DH/TH cases. CONCLUSIONS:Weak and heterogeneous staining of LEF1 can be seen in all the BCLs with and without MYC-R. Strong and uniform staining of LEF1 is highly characteristic of EBV-negative BL among all aggressive BCLs with MYC-R, while the negative staining of LEF1 is mostly suggestive of DLBCL-MYC-R/DH/TH. Lymphocyte enhancer factor 1 provides additional diagnostic value in the differentiation of BL from other aggressive BCLs with MYC-R, especially in a limited specimen.

In the World Health Organization (WHO) 5th edition, prognosis of gastrointestinal (GI) well-differentiated neuroendocrine tumors (WDNET) depends on proliferation rate, commonly assessed by ki-67 immunohistochemical stain. In daily practice, the gold standard for WHO grade assessment by ki-67 staining, printing a photo of a tumor hotspot, counting the number of ki-67-positive cells out of 500 tumor cells, and calculating a percentage, is time-consuming and many cases are eyeballed. This study investigates the utility of a common tool, the manual cell counter used in hematology smear cell counting, for GI WDNET ki-67 counting. Of 59 resections, the number of cases with a WHO grade difference between gold standard print-and-count and the original report, eyeballing, and hematology counter method, was 23 (39 %), 14 (24 %) and 7 (12 %) cases, respectively. Of 37 biopsies, the number of cases with a WHO grade difference between gold standard print-and-count and the original report, eyeballing, and hematology counter method, was 10 (27 %), 12 (32 %) and 7 (19 %) cases, respectively. For resections, Chi square analysis comparing hematology counter method versus original report, where many cases were likely eyeballed, showed statistically significantly less cases with differing WHO grades from gold standard print-and-count for hematology counter-assessed cases (P = 0.0007), and the same Chi square analysis was marginally not significant (P = 0.09) for hematology counter versus eyeballing. Times taken to perform hematology counter method were statistically significantly lower than times taken for print-and-count. This study suggests the hematology cell counter could strike a reasonable balance between time and accuracy for WDNET resections.

T-cell acute lymphoblastic leukemia/lymphoma (T-ALL) is characterized by the combination of T-cell lineage and the presence of immaturity marker(s). Sometimes, the most common immaturity markers for initial flow cytometry screening in T-ALL may be negative, which can be a diagnostic pitfall. When a lack of common first-line immaturity markers is encountered in combination with gamma/delta T-cell receptor expression, a misdiagnosis of mature gamma-delta T-cell leukemia/lymphoma could be rendered. Here, we discuss two T-ALL cases with the absence of common flow cytometry immaturity markers and positive gamma/delta receptor expression.

While eosinophilic esophagitis (EOE) is defined by histologic presence of eosinophils, a few studies have established the presence of mast cells in EOE and even shown their correlation with symptom persistence despite resolution of eosinophils. Expression of aberrant mast cell markers CD25 and CD2 have not been studied in EOE. This study quantifies the number of hotspot cells per high power field expressing CKIT/CD117, tryptase, CD25, CD2 and CD3 by immunohistochemical stains in endoscopic esophageal biopsies of the following three cohorts: (1) established and histologically confirmed EOE, (2) suspected EOE with biopsies negative for eosinophils, and (3) no history of or suspicion for EOE with histologically unremarkable biopsies. In this study, mast cells were highlighted by CKIT and tryptase in EOE, and not seen in other clinically mimicking cases. There were also significantly higher densities of CD25 and pan-T-cell marker staining in EOE cases. These findings suggest an inflammatory cellular milieu in EOE, beyond just eosinophils, that can be demonstrated by immunohistochemistry, and that invite further study into the role that these cells may play in EOE.

Angiogenesis is a critical component of neoplastic progression, and inflammatory cells within the tumor microenvironment contribute to neoangiogenesis. Prostate-specific membrane antigen (PSMA) is expressed in the neovasculature of various solid tumors, including hepatocellular carcinoma (HCC). Also, CXCR2 + inflammatory cells, including CD15 + neutrophils, play crucial roles in HCC progression. We evaluated the associations between PSMA expression and CXCR2 + inflammatory cells in HCC by immunohistochemistry (IHC). CXCR2 expression and its correlation with PSMA, the PSMA/CD34 ratio, immune markers (CD3, CD15, CD68, and CD163), clinical parameters, and oncologic outcomes were evaluated in 76 HCC and background benign liver tissue. PSMA and the PSMA/CD34 ratio showed a positive correlation with intratumoral CXCR2, but not with intratumoral CD15. Intratumoral CXCR2 + cell count was positively associated with intratumoral CD3, CD15, CD68, and CD163 expression levels. In the benign compartment, CXCR2 was significantly associated with CD15. Metabolic dysfunction-associated steatotic liver disease (MASLD) risk factors and cirrhosis had an opposite effect on CXCR2 + cell count in benign liver tissue. Higher CD15 + cell count in the benign liver was associated with decreased overall survival (OS) and recurrence-free survival (RFS). In HCC, intratumoral CXCR2 + cell count is associated with PSMA expression. Intratumoral and benign compartments had different CXCR2 + inflammatory cell makeup. The immune microenvironment of HCC appears to differ depending on underlying risk factors. Further investigations are warranted to elucidate PSMA biology and assess the potential utility of CXCR2 IHC in PSMA-targeted theranostics.

Syphilis is a bacterial infection commonly transmitted by sexual contact. It has variable manifestations and can mimic other disease processes or infections. This report presents the case of a 48-year-old HIV-positive male who was referred to our head and neck clinic with complaints of tonsillar hypertrophy and ulceration accompanied by a one-month history of ipsilateral cervical lymphadenopathy and facial pain in the setting of recent unexplained weight loss and abnormal radiographic imaging of the neck. In-office tonsillar biopsy and fine-needle aspiration of a neck mass revealed a non-diagnostic atypical lymphoid proliferation. Surgical pathology following an open biopsy in the operating room showed Treponema pallidum infection, which was diagnostic for secondary syphilis.

Patients with rectal cancer undergo more repeat biopsies compared to those with nonrectal colon cancer prior to management. We investigated the factors driving the higher frequency of repeat biopsies in patients with rectal cancer. We compared clinicopathologic features of diagnostic and nondiagnostic (in regard to invasion) rectal (n = 64) and colonic (n = 57) biopsies from colorectal cancer patients and characterized corresponding resections. Despite similar diagnostic yield, repeat biopsy was more common in rectal carcinoma, especially in patients receiving neoadjuvant therapy (p < 0.05). The presence of desmoplasia (odds ratio 12.9, p < 0.05) was a strong predictor of making a diagnosis of invasion in both rectal and nonrectal colon cancer biopsies. Diagnostic biopsies had more desmoplasia, intramucosal carcinoma component and marked inflammation, and less low-grade dysplasia component (p < 0.05). Diagnostic yield of biopsy was higher for tumors with high-grade tumor budding, mucosal involvement by high-grade dysplasia/intramucosal carcinoma without low-grade dysplasia and diffuse surface desmoplasia irre-spective of tumor location. Sample size, amount of benign tissue, appearance, and T stage did not affect diagnostic yield. Repeat biopsy of rectal cancer is primarily driven by management implications. Diagnostic yield in colorectal cancer biopsies is multifactorial and is not due to differing pathologists' diagnostic approach per tumor site. For rectal tumors, a multidisciplinary strategic approach is warranted to avoid repeat biopsy when unnecessary.

Aging is associated with nonresolving inflammation and tissue dysfunction. Resolvin D2 (RvD2) is a proresolving ligand that acts through the G-protein–coupled receptor called GPR18. Unbiased RNA sequencing revealed increased Gpr18 expression in macrophages from old mice, and in livers from elderly humans, which was associated with increased steatosis and fibrosis in middle-aged (MA) and old mice. MA mice that lacked GPR18 on myeloid cells had exacerbated steatosis and hepatic fibrosis, which was associated with a decline in Mac2+ macrophages. Treatment of MA mice with RvD2 reduced steatosis and decreased hepatic fibrosis, correlating with increased Mac2+ macrophages, increased monocyte-derived macrophages, and elevated numbers of monocytes in the liver, blood, and bone marrow. RvD2 acted directly on the bone marrow to increase monocyte-macrophage progenitors. A transplantation assay further demonstrated that bone marrow from old mice facilitated hepatic collagen accumulation in young mice. Transient RvD2 treatment to mice transplanted with bone marrow from old mice prevented hepatic collagen accumulation. Together, this study demonstrates that RvD2-GPR18 signaling controls steatosis and fibrosis and provides a mechanistic-based therapy for promoting liver repair in aging.

Colorectal cancer is the third leading cause of cancer-related death, and its incidence is rising in the younger patient population. In the past decade, research has unveiled several processes (underlying tumorigenesis, many of which involve interactions between tumor cells and the surrounding tissue or tumor microenvironment (TME). Interactions between components of the TME are mediated at a sub-microscopic level. However, the endpoint of those interactions results in morphologic changes which can be readily assessed at microscopic examination of biopsy and resection specimens. Among these morphologic changes, alteration to the tumor stroma is a new, important determinant of colorectal cancer progression. Different methodologies to estimate the proportion of tumor stroma relative to tumor cells, or tumor stroma ratio (TSR), have been developed. Subsequent validation has supported the prognostic value, reproducibility and feasibility of TSR in various subgroups of colorectal cancer. In this manuscript, we review the literature surrounding TME in colorectal cancer, with a focus on tumor stroma ratio.

Primary hepatic large B-cell lymphoma (PHLBCL) is a non-Hodgkin large B-cell lymphoma, arising in the liver, without apparent evidence of extrahepatic involvement at diagnosis. Due to its rarity, and, in many cases, a lack of prior history of lymphoma, PHLBCL is not usually included in the initial differential diagnoses for large cell liver neoplasms with a poorly-differentiated appearance. If diagnosed, many patients with PHLBCL show favorable responses to chemotherapy. Although clinical features and oncologic outcome of primary hepatic large B-cell lymphoma are relatively well-described in the literature, histopathologic features are not well-documented. This review summarizes the clinical features, morphology, immunophenotype and available genetic data of PHLBCL. Significant features of PHLBCL from the literature include: female predilection, hepatomegaly, abdominal pain, elevated liver enzymes, a variable number of liver lesions, ki-67 proliferation index of at least 60% and no predominance of either the germinal center or non-germinal center subtypes of diffuse large B-cell lymphoma.

Background:The correlation of intra-operative frozen section diagnosis with the final diagnosis on permanent sections plays a significant role in evaluating liver biopsies for transplant evaluation.The purpose of this study is to investigate the discrepancy between the intraoperative frozen section and permanent section assessment of hepatic steatosis.We aim to reduce errors during frozen section interpretation as it could exclude an otherwise acceptable organ.Design: A retrospective analysis was performed on all frozen sections performed on liver specimens in our institution between April 2017 and July 2021.A total of 264 cases were received.Out of them, 61 cases were included in the study, while 203 cases were excluded due to the concern for malignancy.We then calculated the discrepancy rate between frozen and permanent sections.Results: Out of 61 cases, 20 (32%) cases showed discrepancies between the frozen and the permanent sections.13 (65%) cases showed discrepancies in macrovesicular steatosis, ranging from 1-25%.Four cases (6%) showed a major discrepancy of >10%.In all cases, the percentage of macrovesicular steatosis was described more during the intraoperative consultation than the permanent section.Sixteen (80%) cases showed discrepancies in microvesicular steatosis ranging from 3-30%, and 9 (15%) cases showed a major discrepancy of >10%.Contrary to macrovesicular steatosis, microvesicular steatosis was described more in the permanent section than the frozen section in some (2/20) cases. Conclusions:Our study found considerable discrepancies for both macrovesicular and microvesicular steatosis interpretation between frozen and permanent sections.The extent of steatosis can be misinterpreted during intraoperative consultation because of artifacts produced during frozen section due to multiple factors, including air drying quickly, water droplets freezing in the tissue during processing and much larger size of the hepatocytes with steatosis as compared to normal hepatocytes.Although a significant degree of microvesicular steatosis is not considered an absolute contraindication to transplantation, it is considered a risk factor for early hepatic dysfunction after orthotopic liver transplantation in patients with infections and other immunocompromised conditions.Awareness of these issues can help increase the diagnostic accuracy of donor liver biopsies during intraoperative frozen section interpretation.

Nodular histiocytic/mesothelial hyperplasia (NHMH) is a benign entity that can simulate malignancies histologically. NHMH was initially described in 13 hernia sacs in 1975. Since then, several cases and case series of NHMH have been reported in the literature with variable nomenclatures. It is always an incidental finding seen in a wide range of patient populations with no predilection for gender, age or race. It is most commonly found on mesothelium-lined surfaces such as peritoneum but can also be seen at other sites. It is hypothesized that NHMH occurs due to irritation of mesothelial surfaces and interaction of adhesion molecules. The histologic mimicry by NHMH of malignant processes can pose a diagnostic challenge. This review aims to highlight clinical and pathological aspects of NHMH and to cover common differential diagnoses with special attention to those pertaining to gastrointestinal tract pathology.