Bcl-2 Positivity Research Articles

A Rare Case of Signet Ring Cell Lymphoma and Review of the Literature

Signet ring cell lymphoma (SRCL) is a non-Hodgkin's lymphoma with a very rare variant. Although this morphology is frequently seen in follicular lymphoma, it can also be observed in the group of diffuse large B-cell lymphomas. A seventy-six year old woman with known diagnosis of gastric adenocarcinoma, tubular type, moderately differentiate presented with a mesenteric lymphadenopathy with high FDG uptake (SUVmax: 21.3) in PET/CT during follow-up. A tru-cut biopsy was performed for histopathological diagnosis. Diffuse infiltrative singet ring neoplastic cells showed negativity for PanCK, CK7, CK20, S100, SMA, calretinin and vimentin. The panel was then expanded to include SRCL, a rare variant of lymphoma. Additional immunohistochemical evaluation revealed positivity for CD20, CD19, PAX-5 and Bcl-2. Ki-67 proliferation index was about 80%. CD3, CD30, Myc, Bcl-6, ALK, Cyclin-D1, CD23, CD10, CD21, and MUM-1 were negative. EBER was also negative by chromogen in situ hybridization (CISH). Based on these data, diffuse large B-cell lymphoma (DLBCL) was considered. We herein reported a case of signet ring cell lymphoma discussed its clinical and morphological features with regard to the literature.

DICER1 Syndrome in a 25-Year-Old Female: Autopsy Case Report of Mixed Sex Cord-Stromal and Primitive Sarcoma Tumors with Diverse Differentiation Patterns

Abstract Introduction/Objective DICER-1 syndrome is a rare disorder characterized by germline mutations in the DICER1 gene, known to confer a lifetime risk of developing a variety of benign and malignant pathologies. This syndrome typically affects young individuals, though it exhibits exceedingly variable and relatively low penetrance of the neoplastic manifestations. Methods/Case Report We report on a 25-year-old woman with a history of metastatic DICER-1 related mixed pattern sex-cord stromal tumor of the ovary and primitive sarcoma of the liver. Her treatment involved extensive surgeries, including oophorectomy, salpingectomy, and partial hepatectomy, and multiple cycles of chemotherapy. Antemortem surgical pathological analyses revealed a poorly differentiated, primitive sarcoma in the liver and a sex cord-stromal tumor with Sertoli-Leydig and juvenile granulosa cell tumor-like features. The liver tumor exhibited a primitive spindle cell sarcoma with anaplastic features as well as chondrosarcomatous and rhabdomyosarcomatous patterns, suggesting a primary DICER1-related sarcoma. Immunohistochemistry confirmed the tumor’s complex multilineage differentiation, showing variable positivity for CD99, vimentin, CD10, BCL2, and Glypican-3. Positivity for Desmin and MyoD1 was focal, while the tumor was negative for inhibin, calretinin, AE1/3, AFP, and beta-catenin, overall supporting a DICER1-associated sarcoma diagnosis. She eventually died from terminal cardiac arrest secondary to complications from her metastatic cancer. An autopsy revealed a significant abdominopelvic mass leading to hemoperitoneum and extensive organ involvement, highlighting the aggressive nature of DICER1-associated malignancies. Results (if a Case Study enter NA) NA Conclusion This case underscores the importance of recognizing the broad manifestations of DICER-1 syndrome for accurate diagnosis, genetic counseling, and tailored management. Highlighting tumor morphology and immunohistochemical features enriches our understanding of DICER-1 pathology, advancing diagnosis and treatment prospects for affected individuals.

A Diagnostic Challenge in the Biopsy of a Mammographic Abnormality

Abstract Introduction/Objective Primary breast marginal zone lymphoma (MZL) is an uncommon subtype of extranodal lymphoma, and its diagnosis presents challenges, particularly in distinguishing it from lymphoplasmacytic lymphoma (LPL). MYD88 L265P mutation has been identified in a subset of marginal zone lymphomas, comprising 6-9% of cases. This genetic alteration further complicates the differentiation between MZL and LPL in breast tumors. We present a case highlighting the diagnostic complexities associated with primary breast MZL. Methods/Case Report A 71-year-old female patient underwent mammographic screening, which revealed a suspicious lesion in her left breast. Subsequent PET scan showed a hypermetabolic area consistent with a primary breast lesion. Biopsy histology exhibited a diffuse atypical lymphoid infiltration with varying proportions of neoplastic lymphocytes. Immunohistochemical analysis revealed positivity for CD20, PAX5, BCL2, CD138, MUM1, and negativity for CD3, CD5, Cyclin D1, CD10, CD23, CD34, BCL6, TDT, CD30, GATA3, and CK AE1/3. Additionally, there was lambda light chain restriction, and the Ki67 proliferation rate index was approximately 50%. Fish analysis indicated abnormal BCL6 gene rearrangement. Molecular genetic testing confirmed the presence of MYD88 mutation with c.794T>C p.L265P. Notably, bone marrow biopsy showed no abnormalities, with normal hematopoiesis. Serum electrophoresis and immunofixation detected an IgM monoclonal protein with lambda light chain specificity. Results (if a Case Study enter NA) NA Conclusion The diagnosis of primary breast MZL was favored over LPL due to the absence of common LPL- associated symptoms such as bone marrow involvement. However, the distinction between these entities remains challenging, underscoring the importance of comprehensive diagnostic approaches integrating histopathology, immunohistochemistry, and molecular genetics. Further research is warranted to enhance diagnostic certainty in such cases, particularly as the management of MZL and LPL becomes increasingly specific with the advent of novel therapeutic agents and ongoing clinical trials.

Navigating Uncharted Territory: High-Grade B-Cell Lymphoma Coexisting with Warthin Tumor – Lessons Learned from an Unusual Encounter

Abstract Introduction/Objective High-grade B-cell lymphomas (HGBCL) coexisting with Warthin tumors (WT) are infrequently encountered, yet each case offers valuable insights. This introduction sets the stage by highlighting the rarity of such occurrences and emphasizing the importance of thorough evaluation in diagnosing and managing salivary gland neoplasms. Methods/Case Report We present the case of a 78-year-old man with longstanding bilateral parotid gland masses, initially presumed to be benign WT based on prior biopsies. However, surgical intervention unmasked a surprising twist – concurrent presence of HGBCL within the WT. This rare juxtaposition posed a diagnostic and management conundrum, underscoring the importance of thorough evaluation and consideration of atypical presentations. Pathological examination revealed a landscape of large-sized cells with aberrant expression profiles, including CD20, Pax-5, BCL2, and MUM-1 positivity, along with a MYC rearrangement. Despite the rarity of this phenomenon, the case serves as a poignant reminder of the necessity for comprehensive assessment in seemingly benign conditions. Results (if a Case Study enter NA) N/A Conclusion By dissecting this unique encounter, we glean invaluable lessons in diagnostic vigilance, emphasizing the need for heightened awareness and multidisciplinary collaboration in the management of salivary gland neoplasms. This case underscores the significance of recognizing unusual presentations and leveraging them to refine diagnostic and therapeutic approaches, ultimately enhancing patient outcomes and guiding future clinical practice.

Protective Effects of Trimetazidine and Dexmedetomidine on Liver Injury in a Mesenteric Artery Ischemia-Reperfusion Rat Model via Endoplasmic Reticulum Stress.

Acute mesenteric ischemia can lead to severe liver damage due to ischemia-reperfusion (I/R) injury. This study investigated the protective effects of trimetazidine (TMZ) and dexmedetomidine (DEX) against liver damage induced by mesenteric artery I/R via endoplasmic reticulum stress (ERS) mechanisms. Twenty-four rats were divided into four groups: control, I/R, I/R+TMZ, and I/R+DEX. TMZ (20 mg/kg) was administered orally for seven days, and DEX (100 µg/kg) was given intraper-itoneally 30 min before I/R induction. Liver tissues were analyzed for creatinine, alanine ami-notransferase (ALT), aspartate aminotransferase (AST), thiobarbituric acid reactive substances (TBARS), and total thiol (TT) levels. Compared with the control group, the I/R group presented significantly increased AST, ALT, TBARS, and TT levels. TMZ notably reduced creatinine levels. I/R caused significant liver necrosis, inflammation, and congestion. TMZ and DEX treatments reduced this histopathological damage, with DEX resulting in a more significant reduction in infiltrative areas and vascular congestion. The increase in the expression of caspase-3, Bax, 8-OHdG, C/EBP homologous protein (CHOP), and glucose-regulated protein 78 (GRP78) decreased with the TMZ and DEX treatments. In addition, Bcl-2 positivity decreased both in the TMZ and DEX treatments. Both TMZ and DEX have protective effects against liver damage. These effects are likely mediated through the reduction in ERS and apoptosis, with DEX showing slightly superior protective effects compared with TMZ.

Analysis of Immunohistochemical Expression of Bcl-2 in Cases of Psoriasis and Psoriasiform Dermatitis.

Introduction Psoriasis involves rapid cell growth and abnormal differentiation of skin cells. Dysregulation of apoptosis has been proposed in the pathogenesis of psoriasis. The role of Bcl-2 as an anti-apoptotic proteinin pathogenesis has not been studied in detail in these cases.Our study aims to evaluate the expression of Bcl-2 in different skin compartments in psoriasis and psoriasiform dermatitis cases. Materials and methodology An analytical cross-sectional study was performed using paraffin blocks of psoriasis and psoriasiform dermatitis patients between 2022 and 2023. For light microscopy screening, sections were initially stained with hematoxylin and eosin stains. In further sections, a primary antibody against Bcl-2 was applied. The level of Bcl-2 expression in keratinocytes of supra-basal and basalepidermal layers and dermal lymphocytes was evaluated using a scoring system. Results Sixty patients, 30 with psoriasis and 30 with psoriasiform dermatitis were included. Among the histopathological features, parakeratosis (p - 0.038), Munro's microabscesses (p - 0.001), supra-papillary plate thinning (p - 0.004), and increased dermal vasculature (p - 0.001) were significantly associated with psoriasis when compared with psoriasiform dermatitis. Most psoriatic lesions had hypogranulosis whereas it was alternating hypo and hypergranulosis in psoriasiform dermatitis (p - 0.001). Acanthosis was regular in psoriasis lesions (p - 0.036). Bcl-2 expression was seen in dermal lymphocytes in all psoriasis and psoriasiform lesions with significantly stronger positive expression compared to basal and supra-basal layers. Psoriasis cases demonstrated more significant Bcl-2 positivity in dermal lymphocytes and basal layers than psoriasiform dermatitis cases. Conclusion Bcl-2 has stronger expression in dermal lymphocytes and basal layers than supra-basal layers, which comply with the proposed pathogenesis. Increased Bcl-2 expression in psoriasis cases compared with other psoriasiform dermatitis lesions implies the more chronic and recurrent nature of the disease.

High-grade B-cell lymphoma with 11q aberration in the HIV setting: a clinicopathological study of 10 cases and literature review

High-grade B-cell lymphoma with 11q aberration (HGBL-11q) is a distinct lymphoma entity according to the 5th edition of the WHO classification of hematolymphoid tumors. It lacks MYC translocation but carries proximal gains and/or telomeric losses of chromosome 11q. This rare type of B-cell lymphoma is less frequently reported in people living with HIV (PLWH), and its exact frequency remains unclear. Our goal was to retrospectively analyze its frequency in a cohort of aggressive B-cell lymphomas in PLWH, including Burkitt lymphoma (BL, n = 35), diffuse large B-cell lymphoma (DLBCL, n = 48), high-grade B-cell lymphoma, not otherwise specified (HGBL-NOS, n = 13), which was diagnosed as AIDS-related lymphoma (ARL) at our institution. In total, 10/96 (10.4%) cases harbored the typical 11q aberration pattern, predominantly those that had been classified as BL (6/35, 17.1%), DLBCL (2/48, 4.2%), and HGBL, NOS (2/13, 15.4%). We also evaluated 7 cases of AIDS-related HGBL-11q (AR-HGBL-11q) reported in the literature. The median age of our cohort was 35 years, and all the patients were male. Most cases (70%) had a history of HIV infection for over 1 year, and all were involved in lymph nodes (100%), frequently involved extranodal sites (60%), and Ann Arbor stage III/IV. In histomorphology, the cases exhibited diverse cytological features, reminiscent of BL (6 cases), DLBCL (2 cases), and HGBL (2 cases). A comparison of the combined cohort of 17 AR-HGBL-11q cases with 11 ARL cases that lacked both MYC rearrangement and 11q aberration at our institution showed that HGBL-11q cases were characterized by strikingly coarse apoptotic debris (P < 0.001), background rich in eosinophils (P = 0.002), higher expression of the germinal centre marker LMO2 (P = 0.080), lower expression of MUM1 (P = 0.004), BCL2 (P = 0.007), and LEF1 (P = 0.080), and lower positivity for EBER in situ hybridisation (P = 0.027). Notably, one case in our series was EBV-positive, a finding not previously reported in the literature. Furthermore, comparing the prognosis between these two groups, AR-HGBL-11q showed a relatively favorable prognosis (P = 0.15), although the difference was not statistically significant. We analyzed this rare lymphoma entity in the HIV setting and highlighted the importance of integrating histomorphological and immunophenotypic features in its diagnosis and classification.

EP110 - Chyloperitoneum in Follicular lymphoma – presenting as an inguinal hernia

Abstract Introduction Follicular lymphoma is one of the subtypes of slow growing Non-Hodgkin Lymphoma. Rarely, follicular lymphoma can present with chyloperitoneum or chylous ascites which is characterized by a milky-white coloured fluid with raised triglyceride levels. Case Report We present a case of a 60-year-old diabetic male, complaining of a right sided inguinal swelling for 1 year. Examination revealed a reducible right inguinal swelling with a positive cough impulse. The laboratory workup was unremarkable. Ultrasound scan of anterior abdominal wall showed a defect of 2.1 cm in right inguinal region with protrusion of abdominal contents and a positive cough impulse. A diagnosis of right sided reducible direct inguinal hernia was made. Patient was scheduled for Lichtenstein repair. Per-operatively, the hernial sac contained healthy omentum with milky-white ascitic fluid. Omentum was reduced and suture repair was performed. A drain was placed intra-peritoneally. The postoperative course of the patient was uneventful. Ascitic fluid analysis showed high triglyceride levels and no evidence of malignant cells, suggesting chylous ascites. Contrast enhanced CT scan of abdomen and pelvis revealed a large homogenous minimally enhancing soft tissue density retroperitoneal mass in peri aortic and paravertebral location with abdominal lymphadenopathy suggesting retroperitoneal lymphoma. Excisional biopsy of an enlarged inguinal lymph node confirmed follicular lymphoma with positive BCL2 and CD10 markers. Conclusion Follicular lymphoma presents in a variety of ways including chylous ascites in an inguinal hernia and a high index of suspicion is required to diagnose it.

Ameliorative effects of gallic acid on tebuconazole–induced adverse effects in the cerebellum of adult albino rats: histopathological and immunohistochemical evidence

ABSTRACT Tebuconazole (TEB) is a common triazole sterol demethylation inhibitor fungicide utilized to manage a variety of diseases in crops like cereals, fruits, and vegetables. The aim of this work was to assess the effects of TEB on the structure of the cerebellum in adult albino rats and possible protective impact of co-administration of Gallic acid (GA). Four groups of forty adult male albino rats were randomly selected, and the rats in group I received corn oil through daily gavage for 4 weeks. Group II received GA dissolved in the normal saline at a dose of 100 mg/kg through daily gavage for 4 weeks, group III administered with TEB dissolved in corn oil at its acceptable daily intake dose (0.02 mg/kg body weight) through daily gavage for 4 weeks, group IV rats received both TEB and GA. For light microscopic, ultrastructural, and immunohistochemical investigations, cerebellar specimens were prepared. TEB exposure led to neuronal damage in the form of degenerated Purkinje cells with vacuolated cytoplasm, areas of lost Purkinje cells, the basket cells appeared vacuolated with degenerated neuropil, the granule cells clumped with congested areas between them, dilated cerebellar islands, weak positive bcl2 immunoreactions in the Purkinje cells, and numerous GFAP-positive astrocytes. GA mitigated TEB-mediated histological changes in the cerebellar cortex. We concluded that TEB caused Purkinje neurons in the rat cerebellar cortex to degenerate and undergo apoptosis. GA had a neuroprotective benefit against TEB toxicity in the rat cerebellar cortex.

Evaluation of Immunohistochemical Marker Bcl-2 in Epithelial Dysplasia and Squamous Cell Carcinoma of the Oral Cavity.

Squamous cell carcinoma of the oral cavity is the most common malignancy noted globally.Pathogenesis of premalignant and malignant oral lesions is mainly attributed to the alteration in the molecular mechanisms that regulate apoptosis and cell proliferation. B-cell lymphoma gene 2 (Bcl-2) is the anti-apoptotic gene that prolongs cell survival by inhibiting apoptosis and is associated with the aggressive behaviour of malignant tumours. The aim of the study was to evaluate Bcl-2 expression in oral squamous cell carcinoma and dysplastic lesions of the oral cavity and to compare its expression with various grades of dysplasia and carcinoma. A hospital-based cross-sectional study was done on 80 clinically suspected cases of dysplastic and malignant oral cavity lesions received in the histopathology section of the Department of Pathology of Shri BM Patil Medical College Hospital and Research Center, Vijaypura, Karnataka. Out of 80 cases, 40 were squamous cell carcinoma, and 40 were dysplastic lesions of the oral cavity. For each case, two sections measuring 4 μm thickness were prepared. Hematoxylin and eosin staining was performed on one section, and Bcl-2 IHC staining was performed on another. Bcl-2 expression evaluation was done for each case of oral epithelial dysplasia and squamous cell carcinoma. Out of 40 cases of squamous cell carcinoma, 15 were well-differentiated, 22 were moderately differentiated, and three were poorly differentiated. In well-differentiated oral squamous cell carcinoma, Bcl-2 positivity was grade 0 in 66.7% of cases and grade 1 in 33.3% of cases. In moderately differentiated oral squamous cell carcinoma, Bcl-2 positivity was grade 1 in 63.6% of cases and grade 2 in 36.4% of cases. In poorly differentiated oral squamous cell carcinoma, Bcl-2 positivity was grade 1 in 33.3% and grade 2 in 66.7% of cases. Out of 40 cases of dysplastic lesions, 11 cases showed severe dysplasia, 11 cases showed moderate dysplasia and 18 cases showed mild dysplasia. grade 2 positivity was seen in 72.7% of cases of severe dysplasia and 63.6 % of cases of moderate dysplasia. In mild dysplasia, all of the cases showed grade 0 Bcl-2 expression. In poorly differentiated oral squamous cell carcinoma Bcl-2 positivity was high and low in well-differentiated oral squamous cell carcinoma. Bcl-2 expression was higher in severe dysplasia compared to moderate dysplasia, which may indicate aggressive behaviour of tumour in poorly differentiated oral squamous cell carcinoma and severe dysplasia.

Immunohistochemistry-based investigation of MYC, BCL2, and Ki-67 protein expression and their clinical impact in diffuse large B-cell lymphoma in upper Northern Thailand.

Diffuse large B-cell lymphoma (DLBCL) is an aggressive type of non-Hodgkin lymphoma (NHL) that accounts for approximately 25-40% of all NHL cases. The objective of this study was to investigate the protein expression, clinical impact, and prognostic role of MYC, BCL2, and Ki-67 in Thai DLBCL patients. A retrospective analysis was conducted on 100 DLBCL patients diagnosed between January 2018 and December 2019. Immunohistochemistry was used to assess the expression of MYC, BCL2, and Ki-67. The study revealed a significant association between extranodal involvement and positive cases of MYC and BCL2. MYC expressions were associated with Ki-67 expression, while BCL2 positivity was associated with the non-germinal center B-cell (non-GCB) subtype. However, there were no significant differences in the three-year overall survival (OS) and three-year progression-free survival (PFS) rates when using cut-off points of ≥ 40% for MYC, ≥ 50% for BCL2, and ≥ 70% for Ki-67. Notably, DLBCL cases with co-expression of MYC and BCL2 exhibited significantly inferior three-year OS compared to other cases (0% vs. 53%; p = 0.020). Multivariate analysis identified age ≥ 60 years and Eastern Cooperative Oncology Group (ECOG) performance status as independent prognostic factors. In conclusion, MYC, BCL2, and Ki-67 expression can serve as prognostic biomarkers; however, their prognostic value may vary based on the specific cut-off values used. Therefore, determining the appropriate threshold for each biomarker based on individual laboratory analyses and clinical outcomes is crucial.

Antioxidant and Anti-Apoptotic Neuroprotective Effects of Cinnamon in Imiquimod-Induced Lupus.

Despite accumulating evidence correlating oxidative stress with lupus disease activity, the brain redox pathways are still poorly investigated. Cinnamomum cassia, a widely used spice with powerful antioxidant properties, could be a novel therapeutic candidate in lupus. C57BL/6J female mice were divided into five groups: sham, sham-cinnamon, lupus, lupus-cinnamon starting from induction, and lupus-cinnamon starting two weeks before induction. Lupus was induced by skin application on the right ear with 1.25 mg of 5% imiquimod cream three times per week for six weeks. Cinnamomum cassia was given orally, five days per week, at 200 mg/kg. Concomitant to TLR7-MYD88 pathway activation, the p-NRF2/NRF2 and p-FOXO3/FOXO3 ratios were increased in the hippocampus and alleviated by cinnamon treatment. BCL-2 positivity was enhanced in hippocampal neurons and reversed only by preventive cinnamon administration. In vitro, exposure of hippocampal cells to the plasma of different groups induced a surge in oxidative stress. This was associated with an increased t-BID/BID ratio. Cinnamon treatment, particularly in the preventive arm, normalized these modifications. Our study shows a neuroprotective effect of cinnamon by rescuing brain redox and apoptosis homeostasis in lupus, paving the way for its use as a natural therapeutic compound in the clinical management of lupus.

The protective and antiapoptotic effects of Hypericum triquetrifolium Turra against cyclophosphamide-induced lung injury in rats: in vitro evaluation

Objectives: Hypericum triquetrifolium Turra (HTT) has been traditionally used in medical treatments due to its sedative, antiseptic, antiinflammatory, and anthelmintic properties. The present study aims to investigate the lung-protective and antiapoptotic effects of HTT against cyclophosphamide (CP)-induced lung injury in rats. Methods: Thirty-five Sprague Dawley rats were categorized into 5 groups, each consisting of seven members. Phenolic acid and flavonoid contents of this plant were determined. The lung tissue samples cultivated from the rats were examined in histopathological and immunohistochemically for the apoptosis markers of Caspase-3, Bax, and Bcl-2. Results: Histopathological results indicated that structural defects, bleeding areas, and edema had occurred in the lungs of the CP-Alone Group. Besides, Caspase-3 and Bax positivity of the lung cells had also increased while Bcl-2 positivity had decreased. On the other hand, in the HTT+CP Group, HTT was shown to have reversed the aforementioned changes positively. Conclusion: Based on in vivo results, HTT could be a strong protective candidate for CP-induced lung injury and apoptosis

Study of biomarkers p53, Ki-67, Bcl-2, and VEGF in pterygium.

To study the biomarkers present in primary pterygium samples of patients of Indian ethnicity and compare it with the samples obtained from the unaffected conjunctiva of the same eye. A prospective case-control study of 17 eyes in patients above 10 years of age with primary pterygium who underwent pterygium excision using limbal conjunctival autograft technique. The pterygium samples (cases) and conjunctival samples (controls) were sent for immunohistochemical (IHC) staining for the following biomarkers: p53, Bcl-2, Ki-67, and vascular endothelial growth factor (VEGF). The immunohistochemistry of the samples and the controls revealed p53 positivity in 47.05% of pterygium samples and 29.4% of controls ( P < 0.587). Nine cases each in pterygium and control samples were positive for Ki-67 expression. Differences in the staining pattern between the two groups were not statistically significant ( P < 1.000). Bcl-2 positivity was seen in 10 pterygium samples (58.8%) and 12 controls (70.5%), with no statistical difference between the two groups ( P < 0.455). VEGF expression was seen in both epithelial and endothelial cells of the samples and controls, with no statistical difference between the two groups, with P = 1.000 for the epithelial staining and P = 0.637 for endothelial staining. The expression of biomarkers was comparable in both groups. We conclude that pterygium, against common belief, might not be a localized disease process but a global ocular phenomenon where the apparently healthy tissue also has some ongoing disease process at a molecular level.

Unveiling the Rarity: A Case Report on Solitary Fibrous Tumor of the Thyroid Gland.

Solitary Fibrous Tumor (SFT) rarely manifests within the thyroid gland, an organ predominantly associated with epithelial carcinomas. This case report explores the clinical narrative of a 70-year-old patient presenting with a sizable SFT localized in the left lobe of the thyroid, posing diagnostic challenges uncommon in thyroid nodules. The report delves into the clinical history, radiological findings, pathological assessments, and therapeutic interventions, contributing to the limited literature on thyroidal SFTs.The patient's ultrasound revealed a substantial thyroid mass causing tracheal and vascular displacement, categorized as TIRADS 3. Fine needle aspiration indicated mesenchymal origin, prompting further investigation. Contrast-enhanced computed tomography depicted a well-defined lesion with varied enhancement, compressing surrounding structures. Histopathology confirmed a spindle cell proliferation, prompting immunohistochemistry revealing CD34, STAT6, and Bcl-2 positivity, aligning with SFT characteristics.The rarity of thyroidal SFTs poses diagnostic challenges, necessitating reliance on immunohistochemistry for accurate differentiation from other spindle cell neoplasms. Radiological investigations, including ultrasound and magnetic resonance imaging, contribute to preoperative planning. The case underscores the importance of meticulous pathological examination, emphasizing the utility of immunohistochemistry in confirming SFT diagnosis. The report enhances understanding among clinicians, pathologists, and researchers, guiding improved diagnostic accuracy and tailored treatment strategies for future occurrences of thyroidal SFTs.

Translating prognostic quantification of c-MYC and BCL2 from tissue microarrays to whole slide images in diffuse large B-cell lymphoma using deep learning

Backgroundc-MYC and BCL2 positivity are important prognostic factors for diffuse large B-cell lymphoma. However, manual quantification is subject to significant intra- and inter-observer variability. We developed an automated method for quantification in whole-slide images of tissue sections where manual quantification requires evaluating large areas of tissue with possibly heterogeneous staining. We train this method using annotations of tumor positivity in smaller tissue microarray cores where expression and staining are more homogeneous and then translate this model to whole-slide images.MethodsOur method applies a technique called attention-based multiple instance learning to regress the proportion of c-MYC-positive and BCL2-positive tumor cells from pathologist-scored tissue microarray cores. This technique does not require annotation of individual cell nuclei and is trained instead on core-level annotations of percent tumor positivity. We translate this model to scoring of whole-slide images by tessellating the slide into smaller core-sized tissue regions and calculating an aggregate score. Our method was trained on a public tissue microarray dataset from Stanford and applied to whole-slide images from a geographically diverse multi-center cohort produced by the Lymphoma Epidemiology of Outcomes study.ResultsIn tissue microarrays, the automated method had Pearson correlations of 0.843 and 0.919 with pathologist scores for c-MYC and BCL2, respectively. When utilizing standard clinical thresholds, the sensitivity/specificity of our method was 0.743 / 0.963 for c-MYC and 0.938 / 0.951 for BCL2. For double-expressors, sensitivity and specificity were 0.720 and 0.974. When translated to the external WSI dataset scored by two pathologists, Pearson correlation was 0.753 & 0.883 for c-MYC and 0.749 & 0.765 for BCL2, and sensitivity/specificity was 0.857/0.991 & 0.706/0.930 for c-MYC, 0.856/0.719 & 0.855/0.690 for BCL2, and 0.890/1.00 & 0.598/0.952 for double-expressors. Survival analysis demonstrates that for progression-free survival, model-predicted TMA scores significantly stratify double-expressors and non double-expressors (p = 0.0345), whereas pathologist scores do not (p = 0.128).ConclusionsWe conclude that proportion of positive stains can be regressed using attention-based multiple instance learning, that these models generalize well to whole slide images, and that our models can provide non-inferior stratification of progression-free survival outcomes.

Bcl-2 expression and image analysis of premalignant and malignant colonic lesions

Background/aim Colorectal cancer is the third malignancy worldwide with high mortality. The development of colorectal carcinoma is a multiple step process that turns normal cells into malignant ones. One of these steps is inhibiting apoptosis. Bcl-2 is the key regulators of apoptosis and thus inhibits programmed cell death. The relationship between cell death and cell proliferation is balanced through apoptosis. This study aimed to evaluate immunohistochemical bcl-2 expression, nuclear morphometric parameters, and cell cycle values in premalignant and malignant colon lesions. Material and methods Sixty colonic paraffin blocks (10 normal mucosa, 20 adenomas, and 30 carcinomas) from private laboratories and the Pathology Department, National Research Centre, Cairo, Egypt, were included in this study. Bcl-2 expression was evaluated by immunohistochemistry. Nuclear morphometric parameters and cell cycle values were studied using an image analysis system. Results Immunohistochemical results showed expression of bcl-2 in the lower half of normal colonic crypts. Bcl-2 positivity was detected in 53% of carcinomas and 85% of adenomas with significant difference. The percentage of bcl-2 positive cells in carcinomas was significantly decreased with increasing grades. In carcinomas, nuclear area showed significant increase with increasing grades. Nuclear area showed significant difference between high-grade dysplastic adenomas and carcinomas. Carcinomas showed high proportion of aneuploid cells with significant difference than adenomas. Inverse correlation was detected between aneuploidy and bcl-2 positivity. Conclusion Bcl-2 protein has a role in early event of colorectal carcinogenesis. The acceptable reliability of immunohistochemical, nuclear area, and cell cycle analysis may serve as diagnostic and prognostic indicators in benign and malignant colorectal lesions.

The urgency of Burkitt lymphoma diagnosis in fluid cytology-A tertiary care experience.

Burkitt lymphoma (BL) is an aggressive high-grade B-cell non-Hodgkin lymphoma commonly diagnosed in young age and is known to involve extra nodal sites. But the involvement of body fluids by BL is an uncommon presentation. Rapid diagnosis of BL is vital to prevent complications like tumour lysis syndrome. Cytological examination of body fluids continues to be an indispensable tool for rapid diagnosis of BL. In this study, we aim to study the clinical, cytomorphological and immunophenotypic characteristics of BL involving serous effusions and other fluids. In this retrospective study, 17 cases reported as BL in fluid cytology from 2016 to 2022 were collected and reviewed. We performed a comprehensive analysis of the clinical data, cytomorphological features, immunophenotyping data along with the haematological workup of these cases. We have also compared with the histopathological diagnosis for those cases where biopsy was available. BL more commonly involved ascitic fluid (52%), followed by pleural fluid (4 cases) and cerebrospinal fluid (CSF; 4 cases). Primary diagnosis of BL in fluid was done in 88% of the cases. Bone marrow involvement was noted in two cases. Cytological smears showed discrete monomorphous population of medium-sized atypical lymphoid cells with frequent apoptotic bodies. Classic cytoplasmic punched out vacuoles were observed in 88% of the cases. Immunophenotyping data was available for 12 cases in which tumour cells showed positivity for CD20 (100%), CD10 (4 of 7 cases), BCL6 (3 of 5 cases) and cMYC (7 of 7 cases-100%) and were negative for Terminal deoxynucleotidyl transferase (TdT) (11 of 11 cases). Mean Ki67 labelling index was 95%. Histopathological diagnosis was available for 9 cases, and there was 100% agreement between cytological and histopathological diagnosis in 7 cases. Precise diagnosis of BL can be rendered in body fluids by identification of classic cytomorphological features and by performing supportive ancillary tests in fluids for immunophenotyping.

Meta-Analysis of the Prognostic Significance of BCL6+/CD10+ Mantle Cell Lymphoma

Background: Mantle cell lymphoma (MCL) is a type of non-Hodgkin lymphoma (NHL), classically characterized by the translocation of t(11;14). MCL is typically CD10 negative, often attributed to its pre-germinal nature arising from naïve B cells. Increasing cases of CD10+ MCL suggest the possibility of germinal center-derived pathology. Moreover, a unique and rarer BCL6+/CD10+ immunophenotype has been reported in the literature and warrants investigation into its clinicopathologic significance. This meta-analysis was conducted to further investigate the relationship between MCL immunophenotypes and their clinical outcomes. Methods: A meta-analysis was conducted to investigate the relationship between MCL immunophenotypes and clinical outcomes. Endpoints collected included clinical features, overall survival (OS), morphology, immunophenotypes , Ki67%, and cytologic variants. OS data was pooled from multiple studies and assessed using the R programming package survival. A log-rank test was performed to compare OS. The mean differences in OS between BCL6+ and BCL6- MCL for individual studies were calculated and combined to minimize the batch effects. If individual Ki67 indexes were not available, the standard deviation (SD) of the mean difference was calculated based on normal distribution and the sample size of the particular study. The summary statistics across all studies was calculated by averaging all mean differences and pooling individual SDs. The correlations between CD10 &amp; BCL6, BCL6 &amp; blastoid morphology, and BCL6 &amp; SOX11 were tested using Fisher's exact test. Statistical significance was determined by setting the alpha (α) level at 0.05. Results: The meta-analysis included 537 patients (425 males and 112 females). The median age of diagnosis in CD10+ and CD10- MCL was 69 and 61.5 years old, respectively. There were 70 CD10+, 467 CD10-, and 22 BCL6+/CD10+ patients. BCL6 positivity had an odds ratio of 5.11 (95% CI [2.49, 10.46]; p=0.00002386) for CD10 positivity compared to CD10 negativity. The subgroup analysis showed a higher frequency of blastoid/pleomorphic/small morphology variants in BCL6+/CD10+ MCL. Correlation analysis between BCL6 positivity and blastoid/pleomorphic/small morphology did not demonstrate significant correlation (p=0.2423). However, positive correlation was seen between BCL6 and SOX11 (p=0.013). BCL6+ MCL was associated with an inferior median OS compared to BCL6- MCL (BCL6+: 14 months vs. BCL6-: 43 months; p=0.01). Furthermore, BCL6+/CD10+ co-expression was associated with an inferior median OS compared to BCL6-/CD10+ MCL (BCL6+/CD10+: 20 months vs. BCL6-/CD10+: 55 months; p&amp;lt;0.01). Conclusion: Based on the analysis, it was found that BCL6 expression positivity negatively impacts overall survival (OS) in MCL, regardless of CD10 expression. The higher Ki67% observed in BCL6 expression positivity compared to BCL6 negativity suggests the prognostic value of the BCL6 immunophenotype in MCL. Additionally, BCL6 expression was found to be correlated with CD10 and SOX11 expression, indicating the clinical significance of these variables when combined with BCL6 positivity. It is suggested that prognostic scoring systems adjusted for BCL6 could provide further insights into the prognostic categorization, management, classification, and future tailored treatment of MCL variants.

Consolidative Autotransplantation Achieves High Cure Rates in Adverse-Risk Large B Cell Lymphoma

There remains an unmet need to optimize the first-line treatment of patients with high-risk large B cell lymphoma (LBCL), particularly those with a high International Prognostic Index (IPI) score or a positive interim positron emission tomography (PET) scan who experience poor outcomes with R-CHOP. This study was conducted to evaluate the real-world effectiveness of consolidative autologous stem cell transplantation (ASCT) among patients with high-risk LBCL. This retrospective study included consecutive patients with LBCL and IPI score 4 or 5 who underwent consolidative ASCT as part of first-line therapy in Alberta, Canada. Progression-free survival (PFS), overall survival (OS), and disease-specific survival (DSS) were determined using the Kaplan-Meier method. The study cohort comprised 114 patients with median age of 60 years (range, 18 to 73 years), of whom 81 (71%) had an IPI score of 4 and 33 (29%) had an IPI score of 5. With a median follow-up of 5.6 years, the 5-year PFS was 72% (95% confidence interval [CI], 62% to 79%), 5-year OS was 74% (95% CI, 64% to 81%), and 5-year DSS was 80% (95% CI, 71% to 87%). There was no significant difference in PFS among patients with and patients without positive interim PET scans (n = 24), MYC and BCL2 and/or BCL6 rearrangements (n = 26), or central nervous system involvement (n = 15). Consolidative ASCT is associated with high cure rates and favorable survival outcomes in patients with high-risk LBCL and may overcome the adverse prognostic impact of a positive interim PET scan.