S100 Immunohistochemistry Research Articles

Microsecretory Adenocarcinoma of Salivary Glands: An Expanded Series of 24 Cases.

Microsecretory adenocarcinoma (MSA) is a recently described salivary gland tumor with a characteristic histologic and immunophenotypic profile and recurrent MEF2C-SS18 fusions. Because only six cases of MSA have been published, its complete clinicopathologic spectrum is unclear, and its biologic behavior has not been documented. Here, we present an updated and expanded experience of 24 MSA cases. All cases of MSA were obtained from the authors' files. Immunohistochemistry for S100, SOX10, p63, p40, SMA, calponin, and mammaglobin was performed. Molecular analysis was performed by targeted RNA sequencing, SS18 break apart fluorescence in situ hybridization, and/or reverse transcriptase polymerase chain reaction for MEF2C-SS18 fusion. Clinical follow-up was obtained from medical records. A total of 24 MSA cases were collected, from 13 women and 11 men, ranging from 17 to 83 years (mean 49.5 years). The vast majority (23 of 24) arose in the oral cavity, with the palate (n = 14) and buccal mucosa (n = 6) as the most frequent subsites. Tumors showed consistent histologic features including: (1) microcystic tubules, (2) flattened intercalated duct-like cells, (3) monotonous oval hyperchromatic nuclei, (4) abundant basophilic luminal secretions, (5) fibromyxoid stroma, and (6) circumscribed borders with subtle infiltration. The tumors were very consistently positive for S100 (24 of 24), p63 (24 of 24), and SOX10 (14 of 14) and negative for p40 (0 of 21), calponin (0 of 12) and mammaglobin (0 of 16), while SMA (4 of 20) was variable. MEF2C-SS18 fusion was demonstrated in 21 of 24 cases; in the remaining 3 cases with insufficient RNA, SS18 break apart FISH was positive. Treatment information was available in 17 cases, all of which were managed with surgery only. In 14 cases with follow-up (1-216 months, mean 30), no cases recurred or metastasized. MSA is a distinct salivary gland neoplasm with remarkably consistent clinical, histologic, immunophenotypic, and genetic features that generally behaves in an indolent manner following surgery alone. These observations solidify MSA as a unique, low-grade salivary gland carcinoma that warrants inclusion in the next version of the WHO classification of head and neck tumors.

Does repeated gold-nanoparticles administration affect pars distalis hormonal and folliculo-stellate cells in adult male albino rats?

Worldwide, nanoparticles especially gold-nanoparticles (Au-NPs) are widely used in medicine, cancer treatment and cosmetic industry. They are easily conjugated with different biomedical and biological agents and effortlessly absorbed with few side effects. The pars distalis of the pituitary gland is considered as the maestro of the endocrine peripheral glands since it secrets trophic hormones that controls their functions. 5-10% of the non-granular pars distalis cells are folliculo-stellate cells (FSCs) that support the granular cells' functions. The aim of the study was to explore the histological and the biochemical effects of repeated exposure to Au-NPs on the pars distalis in adult male albino rats with highlighting the impact on FSCs. Thirty-six adult male albino rats were divided equally into control group and Au-NPs group (received 40 μg/kg/day of 11 ± 2 nm spherical Au-NPs orally for 2 weeks). Then, rats were euthanized and deposition of Au-NPs in pars distalis was investigated. Biochemical investigations and histological studies including hematoxylin and eosin staining, periodic acid Schiff's reaction, immunohistochemistry (IHC) for S-100, connexin 43 (Cx43) and Cytochrome-C (Cyt-C) as well as electron-microscopic and morphometric studies were carried out. The Au-NPs group demonstrated structural disorganization in the pars distalis, inflammation, congestion and increased extracellular PAS-positive colloid deposition due to the accumulation of Au-NPs. A significant increase in the immunoreactivity of S-100, Cx43 and Cyt-c, along with a significant increase in TNF-a, MDA, and bFGF content in the pituitary homogenates, was noted as compared to the control group. Ultrastructurally, degenerative changes were observed in the secretory cells. FSCs showed proliferation and increased phagocytic activity. Repetitive exposure of adult male albino rats to Au-NPs prompted the accumulation of these nanoparticles in the pars distalis that was accompanied by cellular degeneration and dysfunction of the secretory cell and proliferation of FSCs. Thus, monitoring of the pars distalis hormonal levels might be useful for early detection of some hazardous effects possibly associated with the use of gold-nanoparticles.

Relationship of nerve diameter using S-100 immunohistochemistry with Hirschsprung-associated enterocolitis degrees

IntroductionHirschsprung-associated enterocolitis (HAEC) is a complication with a multifactorial etiology that can cause morbidity and mortality in patients with Hirschsprung disease (HSCR). The histopathological degree of HAEC according to Teitelbaum's criteria can be used to predict the clinical development of HAEC. S-100 immunohistochemistry identifies enteric ganglion cells and nerve cell proliferation, the absence of ganglion cells, and hypertrophy of nerve fibers – all features of HSCR. MethodsPatients were children with HSCR who underwent leveling colostomy or a pull-through procedure; this sample came from the ganglionic segment of dilatation in the distal zone. The histopathological grade of HAEC was examined, and the size of the nerve diameter was measured by immunohistochemical S-100. Data were analyzed with the Spearman rank test and the Fisher's exact test. ResultsThis study had 26 samples, dominated by boys (73.1%) and the age group 2–3 years (38.5%). The histopathological class distribution was reasonably fair except for class V, where no sample was found in this group. Measurement of the dominant nerve diameter was a size of ≥40μm (84.6%). Statistically, the p-value was not significant to confirm the relationship between histopathological class size and size of nerve diameter (r=0.067). ConclusionIf the diameter of the nerve experiencing hypertrophy is higher, the risk of HAEC is greater, but this relationship is not statistically significant.

Tumor innervation and clinical outcome in pancreatic cancer

Pancreatic cancer is a highly aggressive malignancy characterized by poor survival, recurrence after surgery and resistance to therapy. Nerves infiltrate the microenvironment of pancreatic cancers and contribute to tumor progression, however the clinicopathological significance of tumor innervation is unclear. In this study, the presence of nerves and their cross-sectional size were quantified by immunohistochemistry for the neuronal markers S-100, PGP9.5 and GAP-43 in a series of 99 pancreatic cancer cases versus 71 normal adjacent pancreatic tissues. A trend was observed between the presence of nerves in the tumor microenvironment of pancreatic cancer and worse overall patient survival (HR = 1.8, 95% CI 0.77–4.28, p = 0.08). The size of nerves, as measured by cross-sectional area, were significantly higher in pancreatic cancer than in the normal adjacent tissue (p = 0.002) and larger nerves were directly associated with worse patient survival (HR = 0.41, 95% CI 0.19–0.87, p = 0.04). In conclusion, this study suggests that the presence and size of nerves within the pancreatic cancer microenvironment are associated with tumor aggressiveness.

Atypical Pleomorphic Lipomatous Tumor: Expanding Our Current Understanding in a Clinicopathologic Analysis of 64 Cases.

Atypical pleomorphic lipomatous tumor (APLT) is a recently recognized adipocytic neoplasm that lies on a spectrum with atypical spindle cell lipomatous tumor (ASCLT). APLT/ASCLT are included together in the fifth edition World Health Organization Classification of Soft Tissue and Bone Tumours; however limited data on APLT have emerged since its first description in 2017. This study aims to further define the clinicopathologic features of APLT in a large series of 64 cases. Histologic features and ancillary studies were reviewed, and clinical and follow-up data were obtained from referring institutions. Immunohistochemistry for MDM2, CDK4, CD34, Rb, S100, and desmin was performed in cases with available material. Patients were 24 females and 40 males, and the median age was 61 years (range, 20 to 89 y). Tumors arose in upper limb (33%), lower limb (31%), trunk (23%), head and neck (8%), breast (3%), and inguinal region (2%), with a median size of 5.4 cm (range, 1.5 to 14.5 cm). Tumor depth was mostly subcutaneous or deep/subfascial. Microscopically, APLTs were variably composed of atypical spindle and pleomorphic cells, adipocytes, and lipoblasts, often showing infiltrative growth, myxoid or collagenous stroma, and multinucleate floret cells. Mitoses were infrequent and necrosis was consistently absent. By immunohistochemistry, tumors expressed CD34 (63%), S100 (19%), and desmin (28%). APLT showed frequent loss of Rb (79%; 46/58). Rare cases showed staining for MDM2 (2%) or CDK4 (12%); however, fluorescence in situ hybridization was negative for MDM2 amplification in all cases tested (0/22). Follow-up in 28 patients (median duration: 21 mo) revealed a single patient with local recurrence (4%); no patient developed metastatic disease. Despite its frequently infiltrative growth, nuclear pleomorphism, and hypercellularity which can mimic sarcoma, APLT behaves in an indolent manner and should be distinguished from its more aggressive mimics, including atypical lipomatous tumor/well-differentiated liposarcoma and pleomorphic liposarcoma. Immunohistochemistry for CD34, S100, desmin, and Rb (demonstrating loss), as well as exclusion of MDM2 amplification, can support the diagnosis.

Clinicopathological and immunohistochemical behavior of ductal carcinoma of the salivary and lacrimal gland in a Mexican Mestizo population.

Salivary gland tumors are rare and include benign and malignant entities with different behavior and prognosis. Salivary gland carcinoma accounts for 0.2% of all cancers and 5-9% of head and neck carcinomas. We aim to describe the clinicopathological characteristics and discuss the immunohistochemical findings of salivary ductal carcinoma. We obtained 17 cases (2.3%) of salivary ductal carcinoma (SDC) from 727 patients with parotid tumors at our cancer center from a database covering a 22-year period (1996-2018). Two pathologists confirmed the diagnosis and excluded 6 cases. Eleven cases were assessed by immunohistochemistry (IHC) for HER2, estrogen receptor (ER), progesterone receptor (PR), androgen receptor (AR), mammaglobin, P53, GATA3, S100, cytokeratins (7,8,14,18, and 20), P63, PAX8, calponin, and SOX10. Eleven SDC cases were in advanced stage, and 80% had metastasis. All cases were surgically treated, and 40% received different adjuvant chemotherapy regimens. we found that most patients were dead of disease. The histological and immunohistochemical analysis showed that 70% of cases were high-grade, 40% were positive for HER2, and 50% for AR. Moreover, a high Ki-67 proliferative index was detected in all cases. We observed luminal differentiation in 50% of cases. SDC is a rare entity and survival is very poor. It is histologically similar to ductal carcinoma of the breast. However, important differences exist that help to distinguish them in case of synchronous cancers. The clinical behavior of SDC seems to be more aggressive and IHC analysis is useful for designing therapies.

Gastric Schwannoma: The Masquerader amongst Gastric Mesenchymal Tumours

Introduction: Gastric Schwannoma (GS) is a rare gastrointestinal mesenchymal tumour and needs to be distinguished from other common mesenchymal tumours like Gastrointestinal Stromal Tumour (GIST). GS is composed of Antoni A areas with peritumoural lymphoid cuff unlike conventional schwannomas. GS are difficult to differentiate from other mesenchymal submucosal tumours like GIST. The histological features and strong positive immunostaining for S100 protein along with CD117 (Cluster of Differentiation) and Discovered on GIST 1 (DOG1) immunonegativity is required to confirm the diagnosis. Aim: To analyse the histopathological, immunohistochemical, radiological characteristics and follow-up data of GS. Materials and Methods: This was a retrospective descriptive study conducted in a tertiary care hospital in Southern India. There was a total of eight cases of GS retrieved from the Pathology archives from January 2010 to December 2019. The clinical information along with radiology reports were retrieved from the electronic database. The retrieved slides were analysedfor clinicopathological features. The descriptive analysis of the data was done, and the results were presented as mean, frequencies, and percentages. Results: All eight cases of GS presented in the fifth to eighth decade of life with a female preponderance (male to female ratio of 1:3). Six out of eight cases were symptomatic (75%). Radiologically, a differential diagnosis of GIST was considered in all 8 cases (100%). Microscopically, all 8 cases (100%) exhibited fascicles of spindle cells with mild nuclear pleomorphism, prominent peritumoural lymphoid cuff, and few secondary changes. S100 immunohistochemistry was done in six cases of GS and all showed diffuse strong positivity. The remaining two cases were positive for SRY-related High Mobility Group (HMG)-box 10 (SOX). Conclusion: Preoperative diagnosis of GS is difficult due to non-specific endoscopic or radiological findings. In gastric submucosal tumours, GS should be considered as one of the differential diagnosis. The histopathological and immunohistochemical features are considered the gold standard to diagnose GS.

Schwannoma at an unusual locations: Report of two cases and review of literature

Schwannomas are benign tumors of Schwann cells which are commonly seen at head, neck regions, and extremities. Schwannomas at rare locations such as breast and parotid are very uncommon. Here, we present two case reports of breast schwannoma and parotid schwannoma. In first case, 24-year-old female presented with left breast lump which was clinically diagnosed as fibroadenoma and lumpectomy was done. In second case, 50-year-old female presented with left parotid swelling associated with mild pain. Pleomorphic adenoma was suspected clinically and lesion was excised. Histologically, both cases showed hypocellular and hypercellular areas suggestive of schwannoma. Further, the diagnosis was confirmed with S-100 immunohistochemistry marker. Thus, schwannoma should be considered as one of the differential diagnosis for spindle cell lesion in breast and parotid swelling.

Immunohistochemical analysis of the aggregation of CD1a-positive dendritic cells in resected specimens and its association with surgical outcomes for patients with gallbladder cancer

Gallbladder cancer (GBC) is an aggressive malignancy with a poor prognosis. Antigen-presenting dendritic cells (DCs) play a central role in antitumor immunity. DCs expressing CD1a (CD1a-DCs) are considered immature DCs. The aim of this study was to evaluate the clinical impact of CD1a-DC infiltration into GBC tissue. Seventy-five patients with GBC (excluding non-invasive and intramucosal cancer) were enrolled. Immunohistochemistry for CD1a, S100 and CD8 was performed using representative surgically resected specimens. The cases were divided into a high CD1a-DC group (27 cases, 36%) and low CD1a-DC group (48 cases, 64%) according to the degree of CD1a-DC infiltration/aggregation. The high CD1a-DC group contained fewer patients with distant metastasis (P = 0.039) and more patients given postoperative chemotherapy (P = 0.038). The high CD1a-DC group had significantly longer overall survival (P = 0.001) and disease-specific survival (P = 0.002) than the low CD1a-DC group. In contrast, S100-DC and CD8+ tumor-infiltrating lymphocyte statuses were without effect on OS or DSS. The results of multivariate analyses indicated that the degree of infiltration/aggregation of CD1a-DCs was an independent prognostic factor associated with a favorable prognosis after surgery.

Oct-6 transcriptional factor a possible biomarker for leprosy diagnosis

Leprosy is an infectious disease caused by Mycobacterium leprae that affects the skin and nerves. The nerve damage in leprosy may be related to alterations in transcriptional factors, such as Krox-20, Oct-6, Sox-10. Thirty skin biopsies in leprosy patients and 15 non-leprosy skin biopsies were evaluated using RT-qPCR to assess Krox-20, Oct-6, and Sox-10 and these data was related with S-100 immunohistochemistry. Changes in gene expression were observed in the skin and dermal nerves of leprosy patients in Oct-6 and Sox-10. When comparing Oct-6 with S-100 IHC as diagnostic tests for leprosy, Oct-6 showed a sensitivity of 73.3%, and specificity of 100%, while S-100 IHC showed a sensitivity of 96.6% and specificity of 100%. Our data suggest Oct-6 could be an auxiliary biomarker specific to detecting changes in dermal nerves in leprosy and thus useful to health workers and pathologists with no expertise to observe nerve injuries in leprosy.

Perineural and lymphovascular invasion in squamous cell carcinoma of the tongue

Perineural invasion (PNI) and lymphovascular invasion (LVI) may be adverse prognostic indicators in squamous cell carcinoma (SCC) of the tongue. The percentages of histological PNI and LVI were determined in 335 patients with tongue SCC. Sixty tumours originally reported as negative for these features were tested to determine how many more were positive with "immunohistochemical enhancement." PNI was found in 141 (42.1%) and LVI in 51 (15.2%) patients. 79.4% of the 141 patients who had PNI and 72.6% of the 51 with LVI had a T3 or T4 tumour. Lymph node metastasis was identified in 145 (51.2%) of the 280 patients who had undergone neck dissection; 58.2% of the 141 patients with PNI and 80.4% of the 51 patients with LVI had lymph node metastasis. There was a highly statistically significant correlation between PNI with increasing pT (P<.00001) and pN (P<.0001) stage, and a statistically significant correlation between LVI and pT stage (P<.001), the association of LVI with pN status could not be reliably tested statistically. Immunohistochemistry for S100 identified five further cases of PNI, but review of the original H&E showed the feature was present in four and had been missed at original reporting. CD31 identified three further possible cases of LVI and D2-40 none. The endothelium of some vascular channels was positive for both CD31 and D2-40 and cross-reactivity with other cells compromised interpretation. Histological identification of PNI and LVI per se remains of uncertain prognostic significance. "Immunohistochemical enhancement" offered little benefit.

The Increased Densities, But Different Distributions, of Both C3 and S100A10 Immunopositive Astrocyte-Like Cells in Alzheimer's Disease Brains Suggest Possible Roles for Both A1 and A2 Astrocytes in the Disease Pathogenesis.

There is increasing evidence of astrocyte dysfunction in the pathogenesis of Alzheimer’s disease (AD). Animal studies supported by human post-mortem work have demonstrated two main astrocyte types: the C3 immunopositive neurotoxic A1 astrocytes and the S100A10 immunopositive neuroprotective A2 astrocytes. A1 astrocytes predominate in AD, but the number of cases has been relatively small. We examined post-mortem brains from a larger cohort of AD cases and controls employing C3 and S100 immunohistochemistry to identify the astrocytic subtypes. There were a number of C3 immunopositive astrocyte-like cells (ASLCs) in the control cases, especially in the lower cerebral cortex and white matter. In AD this cell density appeared to be increased in the upper cerebral cortex but was similar to controls in other regions. The S100A10 showed minimal immunopositivity in the control cases in the cortex and white matter, but there was increased ASLC density in upper/lower cortex and white matter in AD compared to controls. In AD and control cases the numbers of C3 immunopositive ASLCs were greater than those for S100A10 ASLCs in all areas studied. It would appear that the relationship between A1 and A2 astrocytes and their possible role in the pathogenesis of AD is complex and requires more research.

Perineural Invasion and Postoperative Adjuvant Chemotherapy Efficacy in Patients With Gastric Cancer.

Purpose: There is currently a lack of validated predictors for adjuvant chemotherapy efficacy in patients with gastric cancer (GC). Perineural invasion (PNI) is the process of neoplastic invasion of the nerves, accompanied by tumor microenvironment (TME) changes. TME can determine treatment outcome while the impact of PNI on chemotherapy efficacy remains unknown in GC. We investigated the association between PNI and the efficacy of postoperative adjuvant chemotherapy in patients with resected GC.Methods: Patients who underwent radical resection of stage IB-III GC with or without fluoropyrimidine (FU)-based adjuvant chemotherapy were retrospectively selected from two separate patient cohorts. PNI was confirmed with S100 immunohistochemistry (IHC). Tumor hypoxia and activity of selected pathways were quantified by mRNA-based signature scoring based on publicly available data. A hypoxia biomarker, ERO1A, and a FU resistance biomarker, thymidylate synthase (TS), were assessed by IHC, respectively.Results: Two cohorts included 223 and 599 patients, respectively. Adjuvant chemotherapy significantly improved overall survival (OS) and disease-free survival (DFS) in PNI-positive but not in PNI-negative patients, which was not impacted by stages. Multivariate models showed that adjuvant chemotherapy was an independent predictor for OS and DFS in PNI-positive patients in both cohorts. For TME, PNI-negative tumors were more hypoxic than were PNI-positive tumors, and displayed relative up-regulation of signaling along the pathways that are important in FU metabolism or resistance. Expressions of ERO1A and TS significantly decreased in PNI-positive compared to PNI-negative tumors.Conclusions: PNI might help predict adjuvant chemotherapy benefit in patients with resected GC. Validation in prospective studies is required. Novel treatment strategies need to be developed in PNI-negative patients.

Primary gastric melanoma: a case report of a rare malignancy

ABSTRACT Noncutaneous melanoma is a rare clinical entity, and their primary or secondary nature is often difficult to establish. Few cases of primary gastric melanoma have been described in the literature. We report a case of a 55-year-old male patient with dyspepsia complaints. Esophagogastroduodenoscopy revealed a polypoid mass with blackened areas at the greater curvature of the gastric body, which was histologically compatible with melanoma; positive immunohistochemistry for S100, melan-A, and vimentin. The extensive dermatological exam did not identify a primary lesion.

Unusual ocular Hodgkinʼs-like lymphoma in a dog.

Hodgkin’s disease is a malignant lymphoproliferative disease with various gross morphology. The present paper reports gross and microscopic features of Hodgkinʼs-like lymphoma in a dog. An eight years-old dog was presented to our hospital due to complete blindness associated with the presence of proliferative tissue on the globe surface. The tissue biopsy sample was soft and frigid with high bleeding tendency and was processed for histopathological evaluation. Sections of 5 μm in thickness were stained with haematoxylin-eosin and melan-A and S-100 by immunohistochemistry (IHC) for differential diagnosis with ocular melanoma. Histologically, regarding the negative Melan-A and S100 IHC findings, and particular histological features, a mixed cellularity type of Hodgkin’s disease which included a large number of lymphocytes with different size and shape together with single necrosis was diagnosed. Additionally, Reed-Sternberg cells which had a deeply lobulated nucleus were demonstrated.

Hyalinized Neurofibromas: Not Just Rare Variants in Skin of the Female Breast.

Although classical neurofibromas are commonly encountered skin lesions, histologic variants are infrequent. We report a greater than 15-year retrospective review of a single institution's experience with the histopathologic diagnosis of neurofibroma of the female breast with a focus on the hyalinized variant. An electronic histopathology record review (CoPathPlus; Cerner Corp, North Kansas City, MO) was conducted from January 1, 2000, to October 16, 2015, for all "neurofibroma" diagnoses rendered in "females" at the anatomical site "breast". All cases were microscopically revisited and subclassified into 1 of 10 histopathologic categories. Immunohistochemistry (IHC) for S100, tryptase, and CD117 were performed on 19 hyalinized and 19 age-matched classical neurofibromas. During the study period, 62,021 breast specimens were reviewed at our institution. Of these, 86 (0.14%) were diagnosed as neurofibromas. Subclassification was as follows: 50 classical (58%), 19 hyalinized (22%), 6 diffuse (7%), 5 cellular (6%), 3 myxoid (4%), 2 epithelioid (2%), and 1 plexiform (1%). All hyalinized and age-matched classical neurofibromas were S100 positive. The mean number of IHC-positive mast cells per high-power field (hpf) was 34.5 by tryptase and 26.8 by CD117 for the hyalinized subset and 22.5 by tryptase and 19.3 by CD117 for the classical cohort. Published literature reports a 2.6% incidence of hyalinized neurofibromas at nonspecial cutaneous sites. Our series details a 22% incidence in the breast. Regarding pathophysiology, there is a statistically significant increase in the average number of IHC-positive mast cells per hpf in hyalinized variants when compared with classical neurofibromas of the breast both by tryptase (P = 0.00157) and CD117 (P = 0.00901).

EP1.15-03 SMARCA4-Deficient Thoracic Malignancies: A Unifying Genetic Aberration Across Tumors of Divergent Differentiation

Mutations in ATPase-dependant chromatin remodelling units are one of the most common genetic alterations observed in human cancer. Germline mutations in SMARCA4 encoding for Brg-1 protein, a subunit of the SWI/SNF chromatin modifier unit, are well recognised as the causative genetic event in rhabdoid tumor predisposition syndromes that occur in infants and young children. In recent years, somatic mutations in SMARCA4 have been increasingly identified in many adult-onset malignancies ranging from well differentiated carcinomas to poorly differentiated high grade sarcomas in a variety of anatomical sites, including thorax. Documentation of such tumors is essential to our understanding of the pathogenesis and possible mechanisms of therapeutic targetting. Case 1: A 60-year-old male smoker presented with chronic emphyema thoracis of non-tubercular etiology which was treated by intercostal drainage. He had repeated episodes of blockade of chest drain over the next 6 months and eventually a thoracic window was surgically created. Five months following thoracotomy, patient presented with a mass growing at the site of the thoracic window. No other masses in the lung parenchyma or mediastinal lymphadenopathy was seen. Patient underwent an excision of the granulation tissue-like mass. Formalin fixed paraffin embedded sections were subject to microscopy and immunohistochemistry for vimentin, CD34, MIC2, p53, SALL4, pan-cytokeratin (AE1/AE3), EMA, p40, TTF-1, cytokeratin-7, Hepar-1, desmin, myogenin, CD31, S100, Melan-A, HMB-45, GATA-3, calretinin, WT1, INI-1, brg-1 and hematolymphoid markers. Case 2: A 58-year old male smoker presented with hemoptysis and cough. On evaluation, an endobronchial mass was identified and was excised. Formalin fixed paraffin embedded sections from excised tumor mass was subject to microscopy and immunohistochemistry for cytokeratin 7, cytokeratin 19, epithelial membrane antigen, chromogranin, synaptophysin, cytokeratin 20, CD117, TTF-1, NUT1, Her2neu, GATA3, p40, S100, INI-1 and brg-1. Case 1: Microscopy revealed a tumor centred in the soft tissue of the chest wall ulcerating the overlying skin. No lung parenchymal involvement was seen. The tumor was arranged in sheets composed of monomorphic large tumor cells with abundant eosinophilic cytoplasm and prominent nucleoli showing frequent mitoses and foci of necrosis. No squamous or glandular differentiation was seen. Tumor cells were only immunopositive for vimentin, CD34, MIC2, p53, and SALL4, very focally immunopositive for CK (AE1/AE3) and showed retained INI-1 protein expression. Brg-1 expression was lost in tumor cells leading to a diagnosis of SMARCA4-deficient thoracic sarcoma. Case 2: Microscopy revealed a high grade tumor arising from the main bronchi with parenchymal and tracheal extension ulcerating the overlying squamous epithelium. Tumor cells were arranged in lobules with peripheral palisading and central necrosis. The tumor cells were large with frequent cytoplasmic clearing and frequent mitoses. Tumor cells were immunopositive for CK-7, CK-19, EMA, CG while were negative for others. INI-1 was retained while brg-1 was lost leading to a diagnosis of SMARCA4-deficient carcinoma. Two independant studies have delineated SMARCA4-deficient thoracic sarcomas and SMARCA4-deficient lung carcinomas as distinct clinicopathological entities. Despite a unifying genetic alteration, these tumors appear to show varied histomorphology and immunoprofiles. Long term follow-up and molecular analysis of such tumors is necessary.

3043 Not All Bumps Are Equal, Mucosal Schwann Cell Hamartoma a Rare Subtype

INTRODUCTION: Benign mesenchymal polyps are an interesting group of colonic polyps. There has been a surge in the number of these polyps identified since legislation modified Medicare and began reimbursement for screening colonoscopy in patients at an average risk for colorectal carcinoma. It is important to differentiate between the different types of mesenchymal polyps given that some have correlation with hereditary diseases. CASE DESCRIPTION/METHODS: 66 year old male patient with history of hypertension presents for routine colorectal cancer screening colonoscopy. He is asymptomatic and has no family history of cancer including colon cancer. During the colonoscopy a small 5 mm polyp was found in the rectosigmoid which was removed using cold forceps polypectomy. The pathology was read as a benign mesenchymal polyp. Further staining with S-100 and CD 68 was done which revealed that this polyp was in fact a Schwann cell hamartoma. DISCUSSION: There has been 10 reported cases of mucosal schwann cell hamartoma in literature. Using immunohistochemistry for S100 highlights tissue with neural differentiation expanding the lamina propria of the colonic biopsy and CD68 highlights muciphages. These polyps resemble spindle cell proliferation and other neuronal tumors and are usually limited to the mucosa of the colon with no submucosal extension. They are usually solitary and patients do not have symptoms though a couple of cases reported finding them in the process of workup for diarrhea. Gibson and Hornick supplied the necessary name in 2009 in an attempt to differentiate it from other Schwann cell proliferation which is seen in entities like neurofibroma and ganglioneuroma. The importance of this entity is its lack of association with hereditary cancer syndromes, specifically neurofibromatosis type 1 (NF1) and multiple endocrine neoplasia 2B (RET) which is seen with neurofibromas. Also ganglioneuromatous polyposis and diffuse ganglioneuromatosis are seen in Cowden syndrome, Juvenile polyposis syndrome, MEN2B and NF1 however solitiary ganglioneuroma are not associated with hereditary diseases. It is important to differentiate this entity from others to prevent unnecessary and aggressive testing and treatment. Pathologists should include this differential as part of S 100 positive spindle cell proliferative lesions and gastroenterologists should be aware of the benign nature of this pathology.

Intraosseous xanthoma of the mandible: A multi-institutional case series with a literature review.

The aim of the present study was to report the clinicopathologic, radiographic and immunohistochemical features of five South American cases of intraosseous xanthomas of the mandible and to compare them to those detected in a literature review. Clinical data were collected from the records of three Oral and Maxillofacial Pathology services in South America and compared with those compiled from a literature review based on a search of three electronic databases (PubMed, Web of Science and Scopus). All cases were evaluated by haematoxylin and eosin staining and immunohistochemistry for CD68 and S-100. The series comprised four females (80%) and one male (20%) with a mean age of 23.3±10.9years (range: 13-45years). In four cases, there was involvement of the posterior region of the mandible (80%). The lesions presented radiographically as unilocular (60%) radiolucencies with punched-out margin (80%). All cases predominantly consisted of CD68-positive and S-100-negative xanthomatous cells. No recurrences were observed after curettage, with a median follow-up of 27months. Intraosseous xanthoma of the jaws is a rare benign disorder. We report here five additional cases affecting the mandible, for a total of 36 cases of the jaws reported in the literature. Overall, this lesion has predilection for posterior sites of the mandible of asymptomatic young adults.

Rosai-Dorfman Disease of the Breast With Variable IgG4+ Plasma Cells: A Diagnostic Mimicker of Other Malignant and Reactive Entities.

Rosai-Dorfman disease (RDD) is an uncommon disorder, characterized by an atypical expansion of histiocytes which classically shows emperipolesis and immunoreactivity with S-100 protein. RDD affects the lymph nodes as well as extranodal sites; however, RDD of the breast is exceptionally rare. Herein, we describe the histopathologic features of 22 cases of RDD occurring in the breast, with an emphasis on the differential diagnosis. All cases were notable for an exuberant lymphocytic infiltrate with and without germinal center formation, and the majority (19/22) showed numerous plasma cells: 5 to 132/high-power field (HPF). IgG and IgG4 immunohistochemical stains were available for 13 cases; in no instance were criteria for IgG4-related sclerosing disease met, though in a single case the IgG4/IgG ratio was increased to 25%. Sclerosis was present in the majority of cases (18/22), and was frequently prominent. RDD cells showing emperipolesis were present in all cases (22/22), and ranged from rare (<1/50 HPF) to numerous (>50/50 HPF). Two of the cases in our series were initially misdiagnosed as inflammatory myofibroblastic tumor and plasma cell mastitis with granulomatous inflammation. As emperipolesis can be indistinct, the presence of stromal fibrosis and a prominent lymphoplasmacytic inflammatory infiltrate should prompt a careful search for the characteristic histiocytes, which can be aided by the use of S-100 immunohistochemistry.