Epithelial to mesenchymal plasticity and differential response to therapies in pancreatic ductal adenocarcinoma.

Transcriptional profiling has defined pancreatic ductal adenocarcinoma (PDAC) into distinct subtypes with the majority being classical epithelial (E) or quasi-mesenchymal (QM). Despite clear differences in clinical behavior, growing evidence indicates these subtypes exist on a continuum with features of both subtypes present and suggestive of interconverting cell states. Here, we investigated the impact of different therapies being evaluated in PDAC on the phenotypic spectrum of the E/QM state. We demonstrate using RNA-sequencing and RNA-in situ hybridization (RNA-ISH) that FOLFIRINOX combination chemotherapy induces a common shift of both E and QM PDAC toward a more QM state in cell lines and patient tumors. In contrast, Vitamin D, another drug under clinical investigation in PDAC, induces distinct transcriptional responses in each PDAC subtype, with augmentation of the baseline E and QM state. Importantly, this translates to functional changes that increase metastatic propensity in QM PDAC, but decrease dissemination in E PDAC in vivo models. These data exemplify the importance of both the initial E/QM subtype and the plasticity of E/QM states in PDAC in influencing response to therapy, which highlights their relevance in guiding clinical trials.

Granulomatous Rosacea Versus Lupus Miliaris Disseminatus Faciei-2 Faces of Facial Granulomatous Disorder: A Clinicohistological and Molecular Study.

Granulomatous rosacea (GR) and lupus miliaris disseminatus faciei (LMDF) are 2 forms of facial granulomatous diseases. Although they show some morphological overlap, they have distinct clinical presentation. This study was performed to demonstrate the clinical and histological features of GR and LMDF and to establish their relationship to tuberculous etiology by molecular technique. All the cases of GR (n = 20) and LMDF (n = 10) diagnosed on skin biopsy over the past 6 years were reviewed along with their clinical detail. Polymerase chain reaction (PCR) was performed using primers specific for Mycobacterium tuberculosis. The mean age of patients with GR was 45 years 10 months (range 18-75 years) as compared to 33 years 5 months (range 18-57 years) in patients with LMDF. The GR cases comprised 13 men and 7 women patients, whereas all 10 LMDF cases were seen in men. GR cases had papular lesion over an erythematous base on face, whereas LMDF cases had papular/nodular/nodulocystic lesions on the face and neck. Histologically, GR cases showed small granulomas without necrosis in a background of variable lymphoid infiltrate and dilated capillaries, whereas LMDF showed large granulomas with caseous necrosis and minimal inflammation. Five cases (25%) of GR showed degenerating Demodex folliculorum mites. No case of GR or LMDF showed positivity for mycobacterial polymerase chain reaction. Despite some similarities, GR and LMDF show distinct clinical and histological features. Thus, LMDF is a distinct clinicopathological entity separate from the GR, with different etiopathogenesis. However, none of the conditions are related to a tuberculous etiology.

Granuloma Annulare-Like Granulomatous Reaction to Red Tattoo Pigment.

Cutaneous reactions to tattoos can be attributed either to trauma or to the exogenous pigment introduced into the skin. Red pigment is associated with a high sensitizing potential and is the most frequently implicated pigment inducing various types of histological reactions. Herein, we describe a patient with red tattoo pigment-induced granulomatous dermatitis that histologically revealed a very rare granuloma annulare-like reaction.

IgG4-related inflammatory pseudotumor: A systematic review of histopathological features of reported cases.

OBJECTIVES: There is marked inconsistency in reporting the key features of IgG4-related inflammatory pseudotumor (IPT) cases. We aimed to analyze the various aspects of IgG4-related IPTs and to test the performance of the consensus criteria for their diagnosis. METHODS: PubMed database was searched for IgG4-related IPT cases. The data regarding patient demographics, clinical presentation, laboratory findings, histopathological features, and treatment response are extracted and are presented here in a descriptive manner. RESULTS: The study included 40 papers describing the clinicopathological features of 83 IPTs in 80 patients. Seventeen cases were diagnosed on biopsies; while remaining were diagnosed on excision specimens. Among these, 50 cases were categorized as highly suggestive and 24 cases as probable for IgG4RD; while nine cases had insufficient histopathological evidence of IgG4RD. Two cases diagnosed on biopsies having insufficient evidence of IgG4RD showed partial or no response to steroids; while 12/14 cases (85.71%) diagnosed on biopsies that were histologically suggestive or probable for IgG4RD showed prompt response to steroids. CONCLUSION: Many reports have not specifically mentioned the full histopathological findings of IgG4-related IPTs that may hinder in refining the diagnostic criteria of IgG4RD. The IgG4-related IPTs diagnosed on biopsies with requisite features showed prompt response to steroids indicating specificity of histopathological findings in predicting treatment response.

Isolated benign primary cutaneous plasmacytosis in an adult Indian male.

Primary cutaneous plasmacytosis (PCP) is an uncommon reactive lymphoplasmacytic disorder of uncertain etiology. It has been mainly described in patients of Japanese descent, with only few reports in Caucasians and Chinese. We present a case of isolated benign PCP in a 45-year-old man, who clinically manifested with a localized ulcerated nodule overlying a hyperpigmented plaque on the upper back. To the best of our knowledge, PCP from India has not been described before.

Pulmonary Gangrene Due to Rhizopus spp., Staphylococcus aureus, Klebsiella pneumoniae and Probable Sarcina Organisms.

Pulmonary gangrene is a life-threatening condition, which represents the fulminant end of the infectious lung diseases usually caused by polymicrobial infection. Aerobic and anaerobic bacteria act synergistically to produce massive tissue necrosis which might be augmented by the angioinvasive nature of fungi like Mucor. We report a successfully treated case of pulmonary gangrene in a poorly controlled diabetic patient, which was associated with polymicrobial infection. It was caused by Rhizopus spp., Staphylococcus aureus, Klebsiella pneumoniae and unusual anaerobic organism Sarcina. This is the first report describing the presence of Sarcina organisms in a case of pulmonary gangrene. Adequate glycemic control, treatment of coexisting polymicrobial infection and prompt antifungal therapy along with surgical intervention were useful in the index patient. This case also highlights the effectiveness of combined medical and surgical intervention in a case of pulmonary gangrene.

Dysregulated Repeat Element Viral-like Immune Response in Hepatocellular Carcinoma.

Purpose: Dysregulation of viral-like repeat RNAs are a common feature across many malignancies that are linked with immunological response, but the characterization of these in hepatocellular carcinoma (HCC) is understudied. In this study, we performed RNA in situ hybridization (RNA-ISH) of different repeat RNAs, immunohistochemistry (IHC) for immune cell subpopulations, and spatial transcriptomics to understand the relationship of HCC repeat expression, immune response, and clinical outcomes. Experimental Design: RNA-ISH for LINE1, HERV-K, HERV-H, and HSATII repeats and IHC for T-cell, Treg, B-cell, macrophage, and immune checkpoint markers were performed on 43 resected HCC specimens. Spatial transcriptomics on tumor and vessel regions of interest was performed on 28 specimens from the same cohort. Results: High HERV-K and high LINE1 expression were both associated with worse overall survival. There was a positive correlation between LINE1 expression and FOXP3 T-regulatory cells (r = 0.51 p < 0.001) as well as expression of the TIM3 immune checkpoint (r = 0.34, p = 0.03). Spatial transcriptomic profiling of HERV-K high and LINE-1 high tumors identified elevated expression of multiple genes previously associated with epithelial mesenchymal transition, cellular proliferation, and worse overall prognosis in HCC including SSX1, MAGEC2, and SPINK1. Conclusion: Repeat RNAs may serve as useful prognostic biomarkers in HCC and may also serve as novel therapeutic targets. Additional study is needed to understand the mechanisms by which repeat RNAs impact HCC tumorigenesis.

Nodular regenerative hyperplasia - An under-recognized vascular disorder of liver.

INTRODUCTION: Nodular regenerative hyperplasia (NRH) is a rare hepatic vascular disorder which is often associated with wide variety of systemic diseases. Intrahepatic microvascular injury and subsequent altered perfusion state leads to development of non-cirrhotic portal hypertension in many of these patients. Diagnosis of NRH often remains unsuspected clinically and liver biopsy is essential for the diagnosis and exclusion of fibrosis. We herein, present clinicopathological features of 22 NRH cases. In addition we assessed CK7 and CD34 expression in hepatocytes and sinusoidal endothelial cells respectively. RESULTS: Most of the cases were associated with systemic disorders, predominantly immunological, inflammatory and drug-related injuries. Signs and symptoms of portal hypertension were found in 86.4 % patients. Majority of the patients showed a predominant mild cholestatic pattern of liver function tests. Nearly all the (21/22) cases showed CK7 positivity in centrizonal hepatocytes which ranged from <10 % cells to diffuse perivenular positivity extending into the midzonal areas. CD34 positivity in sinusoidal endothelial cells was seen in all the cases, which was prominent in periportal areas in all cases; while perivenular (n = 20) and midzonal (n = 14) areas also showed CD34 positive sinusoidal endothelial cells. CONCLUSION: This study highlights the role of pathologist in the diagnosis of NRH and stresses upon the need for awareness of NRH as a cause of unexplained portal hypertension in patients with underlying systemic diseases. The altered perfusion state in NRH leads to phenotypic shift in centrizonal atrophic hepatocytes and sinusoidal endothelial cells (as depicted by IHC) which may be responsible for development of portal hypertension.

Spindle and Round Cell Sarcoma With EWSR1-PATZ1 Gene Fusion: A Sarcoma With Polyphenotypic Differentiation.

The evolving classification of round cell sarcomas is driven by molecular alterations. EWSR1-PATZ1 fusion positive spindle and round cell sarcoma is one such new tumor entity. Herein, we report 2 EWSR1-PATZ1 fusion positive spindle and round cell sarcomas with overlapping histologic features and polyphenotypic differentiation. The intra-abdominal tumors affected female patients, 31-and 53-year old. Both tumors showed sheets and nests of round to spindle cells, fine chromatin, tiny conspicuous nucleoli, moderate cytoplasm, and thick bands of intratumoral fibrosis. On immunohistochemistry, both tumors showed positivity for CD99, desmin, myogenin, MyoD1, S100, Sox10, CD34, and GFAP and were negative for keratin. Fluorescence in situ hybridization revealed rearrangement at EWSR1 locus. Next-generation sequencing-based RNA fusion assay revealed EWSR1-PATZ1 fusion in both cases. EWSR1-PATZ1 fusion positive spindle and round cell sarcomas show abundant intratumoral fibrosis and polyphenotypic differentiation, thus mimicking a range of tumors including desmoplastic small round cell tumor. The precise classification of this spindle and round cell sarcoma and its relationship to the Ewing sarcoma family of tumors remains to be determined.

Morphologic Overlap Between Inflammatory Myofibroblastic Tumor and IgG4-related Disease: Lessons From Next-generation Sequencing.

Inflammatory myofibroblastic tumor (IMT), a locally aggressive neoplasm capable of metastasis, may show an immunoglobulin (Ig)G4-rich lymphoplasmacytic infiltrate. Prior reports suggest that storiform-fibrosis and obliterative phlebitis aid in the distinction of IMT from IgG4-related diseases. Herein, we highlight the morphologic overlap between the 2 diseases, and emphasize the importance of a multiplex fusion assay in the distinction of IgG4-related disease (IgG4-RD) from IMT. We identified 7 IMTs with morphologic and immunohistochemical features of IgG4-RD; 3 patients were originally diagnosed with IgG4-RD. Demographic, clinical and morphologic data was recorded. We also reevaluated 56 patients with IgG4-RD. We performed immunohistochemistry for IgG4, IgG, ALK, and ROS1. In situ hybridization for IgG4 and IgG was performed in selected cases. A multiplex next-generation sequencing-based RNA assay for gene fusions was performed to detect all known IMT-related gene fusions. All 7 IMTs showed a dense lymphoplasmacytic infiltrate and storiform-type fibrosis, with obliterative phlebitis noted in 3 cases. The neoplastic stromal cells constituted <5% of overall cellularity and stromal atypia was either absent or focal and mild. Elevated numbers of IgG4 positive cells and increased IgG4 to IgG ratio was identified in all cases. Four cases showed ALK related abnormalities: 3 fusions and one alternative transcription initiation; while 2 patients showed ROS1 and NTRK3 fusions. One tumor was negative for known IMT-related gene fusions. All 56 IgG4-RD cases were negative for ALK and ROS1 on immunohistochemistry; 6 cases were negative on the fusion assay. Highly inflamed IMTs are indistinguishable from IgG4-RD both histologically and on immunohistochemistry for IgG4. We advocate scrutinizing patients with presumptive single organ IgG4-RD for IMT and the diagnostic algorithm should include ALK and ROS1 immunohistochemistry and, in selected cases, a next-generation sequencing-based fusion assay that covers known IMT-associated gene fusions.

MDM2 RNA In Situ Hybridization for the Diagnosis of Atypical Lipomatous Tumor: A Study Evaluating DNA, RNA, and Protein Expression.

The distinction of atypical lipomatous tumor/well-differentiated liposarcoma (ALT/WDL) from its benign counterpart, lipoma, may represent a challenge. MDM2 DNA amplification is used as the gold standard as MDM2 immunohistochemistry lacks specificity and sensitivity. Herein, we investigate the diagnostic utility of MDM2 RNA in situ hybridization (RNA-ISH) and compare the test with MDM2 immunohistochemistry and MDM2 DNA fluorescence in situ hybridization (FISH) in benign and malignant lipomatous neoplasms. We evaluated 109 neoplasms including 27 lipomas, 25 spindle cell lipomas, 32 ALTs/WDLs, and 25 dedifferentiated liposarcomas (DDL). The validation cohort included 14 lipoma-like neoplasms that lacked unequivocal features of ALT/WDL and in which MDM2 immunohistochemistry was either equivocal, negative or falsely positive. Immunohistochemistry, automated RNA-ISH and DNA-FISH for MDM2 were performed. Tumors with diffuse nuclear staining or >50 dots per cell on RNA-ISH were considered positive. All lipomas and lipoma variants were negative for RNA-ISH while all ALTs/WDLs and DDLs were positive. Eighty percent (24/30) and 92% (22/24) of ALTs/WDLs and DDLs were positive for MDM2 immunohistochemistry. Lipomas and its variants were negative for MDM2 amplification; 92% and 100% of ALTs/WDLs and DDLs showed MDM2 DNA amplification. The mean percentage of ALT/WDL tumor cells showing MDM2 RNA-ISH positivity was 73% compared with 24% on MDM2 immunohistochemistry. RNA-ISH correctly classified all 10 ALTs/WDLs and all 4 lipomas in the validation cohort. The performance of MDM2 RNA-ISH and MDM2 DNA-FISH are equivalent. MDM2 RNA-ISH can be of diagnostic value in histologically challenging lipomatous neoplasms. The automated MDM2 RNA-ISH assay should allow for more widespread use of MDM2 testing and for a more sensitive and specific diagnosis of ALT/WDL.

Autoimmune Pancreatitis Type 2: Diagnostic Utility of PD-L1 Immunohistochemistry.

BACKGROUND: Autoimmune pancreatitis (AIP) encompasses a heterogenous disease group that includes IgG4-related type 1 AIP and non-IgG4-related type 2 AIP. Clinically and on imaging, type 2 AIP mimics type 1 AIP, other forms of chronic pancreatitis and pancreatic ductal adenocarcinoma (PDAC); therefore, discriminatory markers may aid proper diagnosis. Herein, we examine the expression of PD-L1 and indoleamine 2,3-dioxygenase (IDO1) as a diagnostic tool to distinguish type 2 AIP from other forms of pancreatitis and PDAC. DESIGN: We evaluated 35 pancreatectomy specimens diagnosed with type 2 AIP and potential mimics of this disease including type 1 AIP (n=14), chronic pancreatitis-not otherwise specified (n=10), groove pancreatitis (n=14), and PDAC (n=278). We scored inflammatory infiltrates, fibrosis and atrophy and performed immunohistochemical staining for PD-L1 and IDO1. We validated our findings on a series of endoscopic ultrasound-guided biopsies from patients with suspected type 2 AIP and inflammatory and neoplastic mimics of this disease (n=37). RESULTS: The mean age of patients with type 2 AIP was 50 years with a F:M ratio of 1.2:1. Patients with type 2 AIP showed pancreatic ductal staining for PD-L1 and IDO1 in 69% (24/35) and 60% (15/25) of cases, respectively. PD-L1 reactivity was noted in 3% of patients with other forms of chronic pancreatitis and 3% of PDACs; notably, peritumoral ducts and acini were negative. Eight of 9 endoscopic ultrasound-guided biopsies with pancreatic ductal epithelium from patients with type 2 AIP were positive for PD-L1, while the inflammatory and neoplastic mimics were negative. Collectively, the sensitivity and specificity of PD-L1 as a marker of type 2 AIP was 70% and 99%, respectively. CONCLUSIONS: Ductal PD-L1 reactivity has the potential to distinguish type 2 AIP from other forms of pancreatitis and PDAC.

Spectrum of histopathological changes in patients with non-cirrhotic portal fibrosis.

BACKGROUND AND AIMS: Non-cirrhotic portal fibrosis (NCPF) is a clinical disorder characterized by features of portal hypertension in the absence of significant fibrosis. It is one of the commonest causes of portal hypertension in India. This study aimed to analyze histomorphological spectrum of NCPF in detail. METHODS AND RESULTS: There were 67 specimens from 66 patients which included 43 (65.2%) male and 23 (34.8%) female patients with a mean age of 31 years (range: 7-61 years). The liver function tests showed only a mild derangement. The average length of biopsy was 1.4 cm (median: 1.2 cm, range: 0.8-3.4 cm) and the mean number of portal tracts per biopsy was 11.1 (median: 10, range: 5-30). Most cases showed a combination of histological features; the mean number of histological features per biopsy was 7.4 (median: 7, range: 3-12). Obliterative portal venopathy was seen in 47.8% cases. Portal angiomatosis (61.2%), paraportal shunt vessels (61.2%), portal vein dilatation (74.6%), hypoplastic portal tracts (56.7%), megasinusoids (64.1%), and abnormally dilated central veins (64.1%) were other prevalent features. Portal/periportal fibrosis and perisinusoidal fibrosis were seen in 77.6% and 61.2% cases; none showed bridging fibrosis or cirrhosis. The median hepatic venous pressure gradient (HVPG) and liver stiffness (LS) values were 8 mm of Hg (range: 5-20 mm of Hg) and 9.2 kPa (range: 4.4-26.3 kPa). There was no correlation of HVPG or LS with either portal/periportal fibrosis or perisinusoidal fibrosis. CONCLUSION: Due to relatively non-specific and non-pathognomonic nature, a combination of different histological features in the absence of significant fibrosis and appropriate clinico-radiological background is needed for diagnosing NCPF.

In phyllodes tumour of the breast expression of c-kit but not of ALDH1A1 is associated with adverse clinico-pathological features.

Attempts at identification of an ideal prognostic/predictive biomarker in phyllodes tumour (PT) have not been fruitful so far. Studies evaluating c-kit expression in PT have shown contradictory results. Recently aldehyde dehydrogenase 1A1 (ALDH1A1) was proposed as a stem cell marker for malignant PT but its expression has not been studied in benign and borderline tumours. We aimed to evaluate expression and prognostic significance of c-kit and ALDH1A1 in different grades of PT. Epithelial and stromal c-kit and ALDH1A1 expression were studied in 104 PT cases (86 primary and 18 recurrent tumours) and compared with different clinico-pathological features and recurrence rates. Stromal c-kit expression at 1 % cutoff correlated with increasing tumour grade, larger tumour size, hypercellularity, nuclear atypia, stromal overgrowth, infiltrative margins and mitotic count. These associations, however, were lost with higher (5 or 10 %) cutoffs. Conversely, decreased c-kit expression in the epithelial component correlated with increasing tumour grade, regardless of the cutoffs used. Stromal ALDH1A1 expression did not have significant associations with tumour grade or other adverse clinico-pathological features, regardless of different cutoffs. None of the cases showed significant epithelial ALDH1A1 expression. Expression of c-kit was associated with poorer overall survival (p = 0.011), while ALDH1A1 expression was associated with shorter recurrence-free survival (p = 0.036). In conclusion, c-kit expression was associated with higher tumour grade and adverse clinico-pathological features. However, these associations are cutoff dependent, partly explaining the variability in previously reported studies. ALDH1A1 expression did not have significant correlations with tumour grade and adverse clinico-pathological variables.

A Comparative Study of Inflammatory Myofibroblastic Tumors and Tumefactive IgG4-related Inflammatory Lesions: the Relevance of IgG4 Plasma Cells.

IgG4-related disease is a recently recognized systemic condition characterized by tumefactive lesions at various sites. Inflammatory pseudotumor (IPT), a tumefactive mass lesion with an unknown etiology, belongs to the spectrum of IgG4-related disease. Inflammatory myofibroblastic tumor (IMT), previously considered under the umbrella of IPT, is now classified as a clonal neoplasm. Previously, both the terms were used interchangeably, because of overlapping morphologic features. This study was carried out to compare the morphologic and the immunohistochemical features of these entities and to study the role of IgG4 in their pathogenesis. Thirty-nine cases comprising of IMT (n=18) and IPT (n=21) were retrieved, and their clinical, morphologic, and immunohistochemical features were studied. IMT was more common in children as compared with IPT. IMT cases showed the proliferation of myofibroblastic cells accompanied by a variable inflammatory infiltrate, whereas IPT cases showed predominantly stromal fibrosis and a lymphoplasmacytic infiltrate with a subset of cases showing a storiform fibrosis and obliterative phlebitis. Anaplastic lymphoma kinase-1 (ALK-1) was positive in 12 of the 18 (66.7%) IMT cases, whereas none of the IPT cases showed ALK-1 immunoreactivity. IPT cases showed significantly increased IgG4+ plasma cells (mean, 127.8/high-power fields vs. 17.8/high-power fields) and a higher IgG4/IgG ratio (mean, 48.2% vs. 10.7%) as compared with IMT. Fluorescence in situ hybridization analysis was positive for ALK rearrangement in 6 of the 9 IMT cases tested. In conclusion, most of the IPT cases can be considered as IgG4 related on the basis of their histopathologic features and immunohistochemistry criteria. However, IMT represents a myofibroblastic neoplasm with ALK-1 overexpression and is clearly not IgG4 related.

Coagulation factor VIII, IX and XI levels in north Indian patients with venous thromboembolism: first study from India.

Studies have shown elevated levels of certain coagulation factors as risk factors for venous thromboembolism (VTE). In this study, we investigated the levels of coagulation factor VIII (FVIII), FIX and FXI in north Indian patients with VTE. A total of 123 patients with VTE were screened prospectively for FVIII, FIX and FXI levels and the conventional risk factors - deficiencies of protein C, S and antithrombin, positivity for antiphospholipid antibodies and the factor V Leiden mutation. Age-matched and sex-matched controls were included. VTE was secondary to known circumstantial and thrombophilic risk factors in 66 (53.7%) patients. In 46.3% (idiopathic VTE) patients, no cause was identified. The mean FVIII levels in idiopathic (187 IU/dl) and secondary VTE patients (185.4 IU/dl) were significantly higher compared with controls (129.6 IU/dl; P < 0.001). However, there was no statistically significant difference in the levels of FIX and FXI between patients and controls (P = 0.214 and 0.198, respectively). Patients with elevated FVIII levels had increased risk of VTE compared with controls (odds ratio: 9.4, 95% confidence interval: 4.7-18.79). On logistic regression analysis after adjusting for surgery and presence of antiphospholipid antibodies, this risk remained unchanged (odds ratio: 9.54, 95% confidence interval: 4.68-19.44). A dose-response relationship was observed with progressive increase in FVIII levels. Elevated FVIII levels constitute an independent risk factor for VTE in the north Indian population. Elevated levels of FIX and FXI were not associated with increased risk of VTE.

Recurrent phyllodes tumor in the male breast in a background of gynaecomastia.

Phyllodes tumor of the male breast is an extremely rare entity with only a few reports available in the literature. Though exact etiology for development of phyllodes tumor in the male breast is unknown, hormonal imbalance with excess of estrogen action relative to androgen appears to have significant association. This report describes recurrence of phyllodes tumor with malignant features developing in the background of gynaecomastia in a male breast.

IgG4 related sclerosing mastitis: expanding the morphological spectrum of IgG4 related diseases.

IgG4 related disease (IgG4RD) is a recently recognised condition characterised by mass forming lesions associated with storiform fibrosis, obliterative phlebitis, lymphoplasmacytic infiltrate rich in IgG4 positive plasma cells and elevated serum IgG4 levels. Although rare, mammary involvement has been reported as IgG4 related sclerosing mastitis, the morphological counterpart of a growing family of IgG4 related diseases. A total of 17 cases belonging to mass forming benign inflammatory breast lesions such as plasma cell mastitis, granulomatous lobular mastitis, non-specific mastitis and inflammatory pseudotumour were investigated as a possible member of IgG4 related sclerosing mastitis. Clinical, radiological, histopathological and immunohistochemistry findings were noted in all cases. Cases diagnosed as inflammatory pseudotumour showed all the histopathological features of IgG4RD along with increased number of IgG4 positive plasma cells and IgG4/IgG ratio >40%. However, only a few IgG4 positive cells were seen in plasma cell mastitis, granulomatous lobular mastitis and non-specific mastitis cases. These cases also did not fulfill the morphological criteria for the diagnosis of IgG4 related diseases. IgG4RD should be excluded in plasma cell rich lesions diagnosed on core biopsies by IgG4 immunostaining. This can avoid unnecessary surgery as IgG4 related diseases respond to simple and effective steroid treatment.