Immunohistochemical Correlation Research Articles

Histopathological Spectrum of Gliomas and Its Immunohistochemical Correlation in a Tertiary Care Setup.

Introduction Central nervous system (CNS) tumors pose significant diagnostic challenges due to their varied morphological and differentiating characteristics. Modern advancements in immunohistochemistry (IHC) and molecular pathology have greatly enhanced prognostication, screening, and therapeutic management. Gliomas, a type of tumor originating from glial cells in the CNS, can develop from astrocytes, oligodendrocytes, or ependymal cells. According to the 2021 update, the classification of diffuse gliomas is primarily based on the presence or absence of isocitrate dehydrogenase (IDH1/2) mutations. IDH-wildtype gliomas (glioblastomas) have a significantly poorer prognosis compared to IDH-mutant gliomas (astrocytomas and oligodendrogliomas). Gliomas are highly infiltrative and resistant to treatment, making them largely incurable regardless of their grade and prognosis. Objective This study aimed to determine the histopathological diversity of gliomas and its correlation with protein expressions of IDH, ATRX gene (α-thalassemia/mental retardation syndrome X-linked), Ki-67, and p53 mutations (tumor suppressor gene-53), according to the 2021 World Health Organization (WHO) Classification of CNS Tumors, Fifth Edition. Methods This descriptive cross-sectional study was carried out in the Department of Pathology at a tertiary care center, focusing on various types of gliomas received over a two-year period. A total of 54 specimens of gliomas received from the Department of Neurosurgery were subjected to histopathological examination. Sections were stained using hematoxylin and eosin (H&E), and IHC was performed using four markers (IDH, ATRX, p53, Ki-67) in each case. Results were analyzed according to the 2021 WHO Classification of CNS Tumors, Fifth Edition. Results The majority of individuals were between the age group of 40 and 60 years, showing a male predominance (65%). The most common site was the frontal lobe. Glioblastoma constituted the largest proportion (46.2%) of the total cases, followed by astrocytoma (20.3%), oligodendroglioma (18.5%), pilocytic astrocytoma (7.4%), and ependymoma (7.4%). All 11 cases of astrocytoma exhibited IDH mutation and ATRX loss, with p53 positive in the majority of cases. Strong nuclear p53 immunohistochemical positivity in >10% of tumor nuclei correlates with TP53 mutations. Among 25 cases of glioblastoma, IDH was negative, ATRX was retained in all cases, and 11 cases were positive for p53 mutation. For oligodendroglioma, out of 10 cases, IDH mutation was positive, and ATRX was retained in all cases. p53 mutation was not seen in any case. All cases of pilocytic astrocytoma were negative for IDH and p53 mutations, with ATRX retained in all cases. In all cases of ependymoma, IDH and p53 mutations were negative, and ATRX was retained in all cases. Glioblastomas exhibited the highest Ki-67 expression. Conclusion The 2021 WHO Classification of CNS Tumors, Fifth Edition, was updated, building on previously established concepts and continuing to evolve. The final diagnosis of gliomas relies on a comprehensive combination of clinical evaluation, neuroimaging, pathological examination, and molecular analysis. Nonetheless, histopathological examination, along with IHC, remains the cornerstone of diagnosis.

Clinical Pathological and Immunohistochemical Correlations in Gastric Cancer.

Due to its high aggressiveness and polyclonal tumor state, stomach cancer is considered a severe health problem. In this study, we analyzed Her2 and Ki67 in correlation with patient data for the possibility of prognostic factors. The study included 48 cases of gastric tumors that had been surgically treated in a period of five years. The percentage was statistically significant for intestinal-type adenocarcinomas located in the medio-gastric region (p = 0.05); in the diffuse subtype, there were no Her2 positive samples, and in the mixed subtype only one out of three samples was Her2 positive. Our results confirm the existing data, and we can conclude that this link can be considered a prognostic factor in the progression and treatment effectiveness.

Unusual Presentations of Plexiform Neurofibroma: A Series of Three Cases

Neurofibroma is a benign peripheral nerve sheath tumour, and Plexiform Neurofibroma (PN) is pathognomonic of Neurofibromatosis Type 1 (NF1). It occurs equally in males and females and presents at birth or a very early age. The incidence is 1 in 2500 births per year, with an estimated genital association of 1.8%, where clitoral involvement is very rare in the Indian population. In the present case series, three patients were diagnosed with PN through surgical histopathology and Immunohistochemical (IHC) stains like S-100 and Cluster Differentiation 34 (CD34) at a tertiary care hospital. All three patients were children who had painless, gradually increasing swellings that underwent surgical treatment. Among them, a five-year-old girl presented with painless clitoromegaly, multiple café- au-lait spots, and underwent plastic surgery. She was later clinically diagnosed with NF1 after histopathological and IHC correlation. A two-year-old boy with a firm swelling over his left leg showed hyperintensity and multilobulation on magnetic resonance imaging. A 10-year-old boy with a similar swelling in his right upper arm showed multiple hypoechoic masses on ultrasonography. Both of them were later diagnosed with PN using the same methodology. Although it is benign, there is a risk of malignant transformation in diffuse PNs, and they should be managed by wide excision with a safety margin to prevent recurrence.

Development and validation of radiomics nomograms for preoperative prediction of characteristics in non-small cell lung cancer and circulating tumor cells.

To develop and validate 3 radiomics nomograms for preoperative prediction of pathological and progression diagnosis in non-small cell lung cancer (NSCLC) as well as circulating tumor cells (CTCs). A total of 224 and 134 patients diagnosed with NSCLC were respectively gathered in 2018 and 2019 in this study. There were totally 1197 radiomics features that were extracted and quantified from the images produced by computed tomography. Then we selected the radiomics features with predictive value by least absolute shrinkage and selection operator and combined them into radiomics signature. Logistic regression models were built using radiomics signature as the only predictor, which were then converted to nomograms for individualized predictions. Finally, the performance of the nomograms was assessed on both cohorts. Additionally, immunohistochemical correlation analysis was also performed. As for discrimination, the area under the curve of pathological diagnosis nomogram and progression diagnosis nomogram in NSCLC were both higher than 90% in the training cohort and higher than 80% in the validation cohort. The performance of the CTC-diagnosis nomogram was somehow unexpected where the area under the curve were range from 60% to 70% in both cohorts. As for calibration, nonsignificant statistics (P > .05) yielded by Hosmer-Lemeshow tests suggested no departure between model prediction and perfect fit. Additionally, decision curve analyses demonstrated the clinically usefulness of the nomograms. We developed radiomics-based nomograms for pathological, progression and CTC diagnosis prediction in NSCLC respectively. Nomograms for pathological and progression diagnosis were demonstrated well-performed to facilitate the individualized preoperative prediction, while the nomogram for CTC-diagnosis prediction needed improvement.

Study of gastrointestinal neoplasms, histopathologic and immunohistochemical correlation using HER-2/NEU, CK-7 and CK-20

Study of gastrointestinal neoplasms, histopathologic and immunohistochemical correlation using HER-2/NEU, CK-7 and CK-20

Chromophobe-like carcinoma of the thymus: A clinicopathological and immunohistochemical correlation of 5 cases

Five cases of primary thymic carcinoma with distinct histopathological features resembling chromophobe carcinomas are presented. The patients were four men and one woman ranging in age between 43 and 72 years. Clinically, the patients presented with non-specific symptoms of dyspnea and chest pain. Diagnostic imaging revealed the presence of anterior mediastinal masses. All patients underwent complete surgical resection of their tumors via thoracotomy. Grossly, the tumors measured between 4.0 and 5.5 cm in greatest diameter and were ill-defined neoplasms with infiltrative borders; they were light brown in color and had a lobulated surface. Areas of hemorrhage and necrosis were not identified. Histologically, all tumors shared similar histopathological features, mainly the presence of infiltrative tumor islands separated by a fibrocollagenous stroma. At higher magnification, the neoplastic cellular proliferation was composed of medium-sized, round to polygonal cells with eosinophilic or granular cytoplasm and a clear perinuclear cytoplasmic halo, which imparted a chromophobe-like appearance. Nuclear atypia and mitotic activity were identified. Histochemical stains for colloidal iron were negative while immunohistochemical stains for pancytokeratin, cytokeratin 5/6, and p40 were positive in all cases, supporting squamous differentiation in these tumors. Clinical follow-up information was obtained in three patients all of whom died between 3 and 5 years after initial diagnosis, while two patients were lost to follow-up. The cellular characteristics of these tumors represent an unusual variant of thymic carcinoma that may pose a diagnostic challenge in small biopsies and that could be easily confused with other primary or metastatic tumors.

Inflammatory Conditions of the Pancreatobiliary Tree.

The Pancreatobiliary Pathology Society (PBPS) would like to thank Alain C. Borczuk, MD, and the Archives of Pathology & Laboratory Medicine for again highlighting our society by publishing 3 review articles based on the presentations at the PBPS companion society symposium, which was held at the 2021 United States and Canadian Academy of Pathology (USCAP) meeting. As always, PBPS's mission remains the education of surgical pathologists and cytopathologists about the importance of recent advances in this complex field, which will hopefully transform the way we practice pancreatobiliary pathology. The PBPS fosters excellence and international collaboration in education, research, and the global practice of pancreatobiliary pathology. PBPS became an official society in 2016 and a USCAP companion society in 2018. However, the sharing of knowledge, enthusiasm, and ideas in pancreatobiliary pathology actually began more than 20 years ago as an annual “Pancreas Club” luncheon, held during the annual USCAP meeting, which grew over the years and eventually became the PBPS. The first advisory council members of the Pancreas Club were Volkan Adsay, MD; Ralph Hruban, MD; David Klimstra, MD; Günter Klöppel, MD; and Giuseppe Zamboni, MD. Thanks to their continued dedication to pancreatobiliary pathology and contagious enthusiasm, many other pathologists interested in the field were attracted to join and motivated its transformation into the official 501c3 society that it is today (PBPath.org).Because of the COVID-19 pandemic, the 2021 annual USCAP meeting (and by extension the PBPS companion society meeting) was held virtually. The theme of the 2021 PBPS Companion Society Symposium was “Inflammatory Conditions of the Pancreatobiliary Tree.” It featured 1.5 hours of on-demand educational content provided by 4 invited speakers, as well as a live 30-minute question-and-answer session with the speakers and moderators, Michelle Reid, MD, MS, and Rondell Graham, MBBS. The theme of the 2021 meeting was updates on acute and chronic inflammatory conditions of the pancreatobiliary tree, and it featured 4 outstanding presentations by experts in the field (Barbara Centeno, MD, Vikram Deshpande, MD, Dr Klöppel, and Dr Zamboni) entitled (1) “Cytopathology of Inflammatory Lesions of the Pancreatobiliary Tree” (Centeno), (2) “IgG4-Related (Autoimmune) Pancreatitis” (Deshpande), (3) “Acute and Alcoholic Pancreatitis” (Klöppel), and (4) “Paraduodenal Pancreatitis” (Zamboni).All 4 presentations from the 2021 companion meeting have been converted into review articles and are featured in this issue of Archives of Pathology & Laboratory Medicine. In the first article, “Cytopathology of Inflammatory Lesions of the Pancreatobiliary Tree,” Dr Centeno reviews the cytopathology of inflammatory lesions of the pancreas and bile duct, including the different types of pancreatitis. The cytologic criteria useful for differentiating reactive ductal atypia from adenocarcinoma and other malignant mimics are also discussed, and the application of ancillary techniques for this differential diagnosis is emphasized. In addition, Dr Centeno reviews pertinent and best pathology practices in the application of ancillary immunohistochemical and molecular studies for the differential diagnosis of benign from malignant processes in the bile duct. The second article is entitled “Navigating the Challenges Associated With a Diagnosis of Autoimmune Pancreatitis and IgG4-Related Sclerosing Cholangitis” and is written by Dr Deshpande, along with his colleagues Osman Yilmaz, MD, and Karen Pinto, MBBS, DNB, FRCPath. In this article Drs Yilmaz, Pinto, and Deshpande examine the clinicopathologic features of type 1 and 2 autoimmune pancreatitis and immunoglobulin G4–related sclerosing cholangitis. They emphasize the use of a multimodal approach (clinical, radiographic, serologic, histopathologic, and immunohistochemical correlation) and highlight the distinctive overlapping qualities that can aid in diagnosing these entities and distinguishing them from other fibroinflammatory and/or neoplastic mimics. The authors also discuss diagnostic pitfalls and differential diagnoses and offer an approach to the interpretation of needle biopsies, including ampullary biopsies. The third article is entitled “Acute and Chronic Alcoholic Pancreatitis, Including Paraduodenal Pancreatitis.” It combines the talks of our third and fourth speakers, Dr Klöppel and Dr Zamboni. In this combined article, Drs Klöppel and Zamboni present the current state of pathology and pathogenesis of alcohol-associated pancreatitis, including paraduodenal pancreatitis. In the context of the most important epidemiologic, clinical, and radiologic features, the role of alcohol overconsumption and related macroscopic changes and histopathologic characteristics are addressed. Pathologic findings that distinguish mild from severe pancreatitis, as well as a histologic staging system for chronic pancreatitis, are emphasized. The morphologic features of paraduodenal pancreatitis as well as the anatomic peculiarities associated with it are also described.We are extremely proud of our society and the continued contributions of its members to the field of pancreatobiliary pathology. We hope that you will enjoy these review articles highlighting the experts' perspectives on inflammatory conditions of the pancreatobiliary tree.

The Role of P16, P53, KI-67 and PD-L1 Immunostaining in Primary Vaginal Cancer.

To analyze clinical, pathological and immunohistochemical correlates of survival in vaginal cancer patients. Retrospective analysis of primary vaginal cancer patients, treated at the Department of Gynecology and Gynecological Oncology of the University Hospital Bonn between 2007 and 2021. The study cohort comprised 22 patients. The median age was 63 years (range: 32-87 years). Squamous cell histology was present in 20 patients. Five-year OS in Stage I, II, III and IV was 100%, 56.25%, 0% and 41.67%, respectively (p = 0.147). Five-year DFS was 100%, 50%, 0% and 20.83%, respectively (p = 0.223). The 5-year OS was significantly reduced in the presence of nodal metastasis (p = 0.004), lymphangiosis (p = 0.009), hemangiosis (p = 0.002) and an age above 64 years (p = 0.029). Positive p 16 staining was associated with significantly improved OS (p = 0.010). Tumoral and immune cell PD-L1 staining was positive in 19 and in 16 patients, respectively, without significant impact on OS; 2 patients with metastastic disease are long-term survivors treated with either bevacizumab or pembrolizumab. P16 expression, absence of lymph- or hemangiosis, nodal negative disease and an age below 64 years show improved survival rates in PVC. Tumoral PD-L1 expression as well as PD-L1 expression on immune cells is frequent in PVC, without impacting survival. Within our study cohort, long-term survivors with recurrent PVC are treated with anti-VEGF and immunotherapy.

BRCA1 promoter methylation & its immunohistochemical correlation in sporadic breast cancer.

Studies have shown that apart from hereditary breast carcinomas, breast cancer susceptibility gene 1 (BRCA1) mutations conferring to its loss are seen in sporadic breast carcinomas (SBC) as well. The aim of the present study was to assess BRCA1 methylation in females presenting at King George's Medical University, Lucknow, with SBC by both immunohistochemistry (IHC) and methylation PCR with respect to hormonal profile and various morphological prognostic parameters. The primary objective was to look for the association between BRCA1 protein expression and DNA promoter methylation. 81 mastectomy specimens from SBC of invasive breast carcinoma (no special type) were included in this study. After a detailed morphological assessment, formalin fixed paraffin embedded tissue from a representative tumour area was selected for BRCA1 IHC by heat-mediated antigen retrieval under high pH and DNA extraction and further bisulphate treatment. BRCA1 was studied for methylation by methylated and unmethylated PCR-specific primers. BRCA1 promoter methylation was present in 42/81 (51.9%) participants, with significant BRCA1 protein loss (72.7%; P=0.002). A significant association between BRCA1 loss and hormonal profile was found (P=0.001); maximum in triple negative breast carcinoma (TNBC) (72%; 18/25). Most of the TNBC also harboured methylation (68%). Although not significant grade II and III tumours, lymph vascular invasion, ductal carcinoma in situ, and nodal metastasis (≥3) were seen in a higher percentage in methylated tumours. Mortality in SBC was significantly associated with BRCA1 loss (30.3%; P=0.024). Study results highlight the concept of "BRCAness" in SBC as well. Hence, we can confer that identification of BRCA1 loss in SBC can make it a perfect candidate for poly ADP-ribose polymerase inhibitors or cisplatin-based therapy like hereditary ones.

What's new in the WHO 2022 classification of kidney tumours?

The World Health Organization (WHO) 2022 classification of urinary and male genital tumours (5th edition) has significantly improved our understanding of the morphologic, immunohistochemical, and molecular characteristics of renal tumours. The aim of this review is to outline the most important changes and diagnostic updates in the WHO 2022 classification of kidney tumours. A major change in this edition is the grouping of renal tumours into broader categories that include "clear cell renal tumours", "papillary renal tumours", "oncocytic and chromophobe renal tumours", "collecting duct tumours" as well as adding two categories of "other renal tumours" and "molecularly defined renal carcinomas". Novel entities included in the WHO 2022 classification are eosinophilic solid and cystic renal cell carcinoma (ESC RCC), anaplastic lymphoma kinase (ALK)-rearranged RCC and ELOC (formerly TCEB1)-mutated RCC. The category of "other renal tumours" includes a group of diverse, unrelated renal tumours that do not fit into other categories. The group of "molecularly defined renal carcinomas" reflects recent discoveries in the renal tumour genomics. These molecularly-defined renal entities demonstrate a set of morphologic features reflecting genotype-phenotype relationships. Final diagnosis of such entities rests on phenotypic and immunohistochemical (IHC) correlation, usually associated with IHC surrogate makers that reflect specific genetic abnormalities.

Role of GDF-15 as an Immunohistochemical Marker in Follicular Neoplasms and Lesions of Thyroid

Introduction: A pre-therapeutic distinction between benign and malignant thyroid nodules is critical for deciding the therapeutic strategy, wherein fine-needle aspiration cytology plays a major role. However, there are grey-zone categories in the Bethesda system for reporting thyroid cytopathology, which is currently, the universally accepted pattern for reporting thyroid FNAC. Several immunomarkers studied in these ‘indeterminate’ lesions have proven to be of limited value. Recent molecular studies have shown the growth differentiation factor-15 (GDF-15) gene to be a promising marker in various malignancies; though, there is sparse literature regarding its use as a surrogate immunohistochemical marker, especially in thyroid neoplasms. The present (pilot) study explores its possible utility in the pre-therapeutic distinction of follicular-patterned lesions and neoplasms of the thyroid by testing it initially on histopathologic sections. Objective: To assess the utility of GDF-15 as an immunohistochemical marker in distinguishing common follicular-patterned thyroid neoplasms and lesions. Materials and Methods: GDF-15 immunohistochemistry was performed on 75 surgical specimens of thyroid lesions, comprising 19 adenomatous nodules or follicular hyperplasias, 10 nodular goitres, 17 follicular thyroid adenomas, 8 follicular thyroid carcinomas, 12 follicular variant of papillary thyroid carcinomas, and 9 conventional papillary thyroid carcinomas. All these cases were histologically proven, and their immunohistochemical interpretation was performed using the immunoreactive scoring system. Pearson’s analysis was performed for the immunohistochemical correlation among the study groups. Results: The findings were inconsistent; 16 follicular-patterned malignancies (5 follicular carcinomas and 11 cases of follicular variant of papillary carcinoma) and seven conventional papillary thyroid carcinomas revealed both cytoplasmic and membranous expression of GDF-15. All benign lesions were negative except one follicular adenoma and three follicular hyperplasias, which exhibited patchy or focal GDF-15 positivity. However, three follicular carcinomas, one follicular variant of papillary carcinoma, and two conventional papillary carcinomas were found to be GDF-15-negative. Conclusion: Though there is a literature backup supporting the use of GDF-15 gene analysis in differentiating various follicular-patterned neoplasms, the GDF-15 protein, as an immunohistochemical marker failed to distinguish not only between benign and malignant follicular-patterned neoplasms but also between follicular carcinoma and follicular variant of papillary carcinoma.

Molecular and immunohistochemical testing of bone tumours: review and update.

Primary bone tumours can pose diagnostic problems due to their overlapping radiologic and histologic features. Given the recent advancement in our understanding of the biology of bone tumours, multiple immunohistochemical and molecular markers have been devised to aid in their diagnosis. This review provides brief updates on select bone tumours, including chondrosarcomas, benign chondrogenic tumours, osteosarcomas, benign osteogenic tumours, fibroosseous lesions, vascular tumours, osteoclastic giant cell-rich or cystic tumours, chordoma, adamantinoma, small round blue cell sarcomas, and others. We discuss their salient molecular features and novel immunohistochemical correlates, along with some tips to avoid common diagnostic pitfalls.

The histopathological and molecular diagnosis of myocardial sarcocystosis in sheep, and the immunohistochemical correlation of parasitic lesions with MMP - 2 and MMP - 9

This study was aimed at the histopathological and immunohistochemical level investigate cardiac tissue lesions caused by Sarcocystis spp. in sheep, and thereby, to collect detailed information on the presence of these parasites and the pathogenesis of sarcocystosis in ovine animals. PCR, a molecular diagnostic method, was used for the identification of the parasite species. Microscopic examination revealed that out of the 45 ovine cardiac tissue samples examined 23 contained Sarcocystis spp. cysts. The PCR analysis results showed that out of the 23 cardiac tissue specimens infected with sarcocysts, 7 were determined to be infected with Sarcocystis gigantea and 16 with Sarcocystis tenella. Immunohistochemical examination demonstrated that, semiquantitatively, MMP - 9 staining was stronger than MMP - 2 staining in the periphery of the parasite cysts.

Navigating the Challenges Associated With a Diagnosis of Autoimmune Pancreatitis and IgG4-Related Sclerosing Cholangitis.

The pancreatobiliary tract exhibits a spectrum of heterogeneous fibroinflammatory conditions that may be the result of a primary immune-mediated mechanism, or a reaction to neoplasm. This often results in significant overlap regarding clinical presentation, symptoms, radiographic findings, serology, and histopathology between inflammatory and neoplastic lesions of the pancreas, which can lead to inadvertent surgical intervention. Among the multitude of primary fibroinflammatory pancreatic diseases, autoimmune pancreatitis, including type 1 and type 2 autoimmune pancreatitis, and immunoglobulin G4-related sclerosing cholangitis (IgG4-RSC) are particularly challenging and require a multidisciplinary perspective to reliably make a diagnosis. This is of particular significance because these diseases typically have a favorable prognosis and readily respond to steroid therapy. To present a multimodal approach to highlight distinctive and overlapping qualities that will aid in the diagnosis of these entities. The review and analysis of literature describing autoimmune pancreatitis types 1 and 2 and IgG4-RSC. Diagnosis of autoimmune pancreatitis types 1 and 2 and IgG4-RSC requires a multimodal approach that relies on clinical, radiographic, serologic, histopathologic, and immunohistochemical correlation.

Cytohistologic immunohistochemical correlation of epithelial tubo-ovarian neoplasms: Can cell blocks substitute for tissue?

Cytologic specimens often represent the initial diagnostic material for tubo-ovarian neoplasms resulting from therapeutic paracentesis for patients presenting with high-volume ascites. However, subtyping and immunohistochemical (IHC) characterization, which have implications in preoperative management and downstream ancillary testing, are not routinely performed in many institutions. This study aims to perform cytohistologic correlation of commonly used IHC stains to establish their reliability in peritoneal fluids/washing specimens. A retrospective search of the laboratory information systems was performed to identify peritoneal fluid/washing specimens involved by borderline or malignant epithelial tubo-ovarian neoplasms and concurrent/subsequent surgical resection specimens. Cell blocks and tissue were stained for PAX8, WT-1, p53, p16, Napsin-A, estrogen receptor, and progesterone receptor, and staining between cytological and surgical specimens was compared. A total of 56 case pairs were included, with the following final diagnoses on histological examination: 37 high-grade serous carcinomas, eight clear cell carcinomas, one endometrioid adenocarcinoma, two low-grade serous carcinomas, and eight serous borderline tumors. There was perfect cytohistologic correlation for PAX8 (Lin's concordance correlation coefficient [LINCCC]=1.00) and WT-1 (LINCCC=1.00), substantial/good correlation for p53 (LINCCC=0.96), p16 (LINCCC=0.93), napsin-A (LINCCC=0.91) and ER (LINCCC=0.77), and moderate correlation for PR (LINCCC=0.54). Immunohistochemical correlation between peritoneal fluid and surgical resection specimens for tubo-ovarian neoplasms is high. Common subtypes of tubo-ovarian carcinomas can be reliably distinguished on fluids using IHC.

Immunohistochemical correlation of mast cells and angiogenesis in oral lichen planus

ObjectiveThe study was conceived with an aim to correlate mast cell expression and angiogenesis in oral lichen planus (OLP) and inflamed oral mucosa. DesignAn observational study was performed on fifty tissue blocks of OLP and inflamed oral mucosa which were stained immunohistochemically using mast cell tryptase, CD34 and CD105. The data was analysed using Mann Whitney U-test and Spearman’s rank correlation coefficient test (p < 0.05). ResultsOLP showed significantly higher mast cell density for total and degranulated mast cells and higher microvessel density (CD105) compared to inflamed oral mucosa (p = 0.006, 0.000). Microvessel density, total and mean vascular area (CD34) were higher in inflamed oral mucosa with a non significant difference (p = 0.985, 0.977, 0.720). Mild negative association was observed between mast cells and angiogenesis in OLP (p = 0.879). A significant positive correlation was seen between degranulated mast cells and microvessel density (CD34) in inflamed oral mucosa (p = 0.009). ConclusionMast cells execute different roles in OLP depending upon stage of the disease. We found that although degranulation of mast cells is not the predominant pathway for angiogenesis in OLP, yet is one of the important precursor phenomena in inflamed tissues.

Immuno-histochemical correlation of fibrosis-related markers with the desmoplastic reaction of the mesentery in small intestine neuroendocrine neoplasms

IntroductionSmall intestine neuroendocrine neoplasms (siNENs) will attain more importance due to their increasing incidence. Moreover, siNENs might lead to a desmoplastic reaction (DR) of the mesentery causing severe complications and deteriorating prognosis. The expression of fibrosis-related proteins appears to be the key mechanisms for the development of this desmoplastic reaction. Therefore, this study aimed to investigate the association of the desmoplastic mesentery with specific fibrosis-related protein expression levels.Materials and methodsBy immunohistochemistry, the protein expression levels of four fibrosis-related markers (APLP2, BNIP3L, CD59, DKK3) were investigated in primary tumors of 128 siNENs. The expression levels were correlated with the presence of a desmoplastic reaction and clinico-pathological parameters.ResultsIn the primary tumor, APLP2, BNIP3L, CD59 and DKK3 were highly expressed in 29.7% (n = 38), 64.9% (n = 83), 92.2% (n = 118) and 80.5% (n = 103), respectively. There was no significant correlation of a single marker or the complete marker panel to the manifestation of a desmoplastic mesentery. The desmoplastic mesentery was significantly associated with clinical symptoms, such as flushing and diarrhea. However, neither the fibrosis-related marker panel nor single marker expressions were associated with clinical symptoms.DiscussionThe expression rates of four fibrosis-related markers in the primary tumor display a distinct pattern. However, the expression patterns are not associated with desmoplastic altered mesenteric lymph node metastases and the expression patterns did not correlate with prognosis. These findings suggest alternative mechanisms being responsible for the desmoplastic reaction.

Cytohistological and immunohistochemical correlation of cutaneous neoplastic lesions: Three year retrospective study

: Neoplastic lesions in cutaneous and subcutaneous region comprise a large group of benign and malignant entities of different lineage. Clinical, morphological features and prognosis of these lesions differ a lot. For diagnosis FNAC (Fine needle aspiration cytology) is the first technicque applied followed by histology, immunohistochemisty (IHC) and so on.: Cytological evaluation of cutaneous and subcutaneous neoplasms and correlate with histopathology and IHC. Study of all palpable cutaneous and subcutaneous swellings presenting to cytology OPD (Out patient department) with further histopathological correlation in the three-year duration.: FNA cytosmears of the cases stained with leishman stain in most of cases. Histopathological and IHC correlation done in available cases.: The data are expressed in descriptive statistics measures such as percentages and proportions. Out of 1032 total cases, most of the cases were benign (94.3%) with fewer malignant cases (5.7%). Lipomas 562(56.31 %) were the largest group among benign lesions followed by benign spindle cell lesions 286(28.65%). Metastatic (22, 64.7%) lesions were more in number than primary cutaneous malignancies (12,35.2%). Among adenocarcinomas, 4 metastatic cases (0.38%) from lung and breast each and among squamous cell carcinomas (SCC), 7(0.67%) primary SCC were seen. Biopsy correlation was available in 134(12.98%) cases and IHC done in 14(1.35%) cases.: Cutaneous neoplasms though benign in most of the cases, can be of critical aetiology with dismal prognosis. Hence they should not be taken lightly and diagnosed specifically with the help of imaging and cyohistological study whenever needed.

Vitamin D status in Dupuytren's disease: Association with clinical status and vitamin D receptor expression

Dupuytren's disease (DD) is a progressive fibroproliferative condition involving contractures of the fascia of the palm. Up to now, there are no relevant investigations on patients with DD in case of serum vitamin D deficiency. We hypothesized that transforming growth factor-β1 (TGF-β1) is increased in patients with DD in consequence of vitamin D deficiency, thereby leading to myofibroblast differentiation and subsequent progression of contractures. The aim of this study was to analyze serum vitamin D levels and explore possible clinical and immunohistochemical correlates with vitamin D concentrations in a group of patients with DD. Vitamin D levels were measured in all patients with DD and healthy controls. In the patient group, clinical characteristics were compared between vitamin D deficient and nondeficient subgroups. Diseased palmar fascia samples were obtained from 14 patients undergoing fasciectomy for DD. Correlations between vitamin D levels and vitamin D receptor(VDR), TGF-β1 expression levels in collected fascia samples were evaluated. Vitamin D concentrations were significantly lower in patients than in healthy controls. In addition, total extension deficit of involved fingers was higher in vitamin D deficient patients. Moreover, a positive correlation was found between vitamin D levels and expression of VDR in pathologic fascia in patients undergoing fasciectomy for contracture. Serum vitamin D levels were found to be low in patients with DD. Expression of VDR was lower in the vitamin D deficient group. The results suggest a potential link between vitamin D status and DD but causation is not yet established. The potential role of vitamin D and its interaction with VDR and the TGF-β1 signaling pathway in the pathogenesis of DD needs to be explored further.

Practical immunohistochemistry in the classification of salivary gland neoplasms.

Diagnosis of salivary gland neoplasms can be challenging for surgical pathologists due to low incidence of tumors as well as overlapping histologic features. On small biopsy, the most important information to be conveyed for clinical management is the distinction between a benign/low grade tumor and a high grade carcinoma. This review will discuss the differential diagnosis of salivary gland tumors based on four broad morphologic patterns: basaloid/tubular/cribriform, (micro)cystic/secretory/mucinous, solid-nested/clear-spindled, and oncocytic/oncocytoid. With the assistance of immunohistochemistry, demonstration of the number of cell types (mainly epithelial versus myoepithelial/basal) can further subclassify tumors within these morphologic categories. Additional tumor-specific immunomarkers are useful in some cases. Underlying tumor-specific genetic anomalies can be of value, however, immunohistochemical correlates are only available for some. When used judiciously, in the correct morphologic context, and with knowledge of their limitations, immunohistochemical stains can aid in differentiating tumors with similar morphology.