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Mallory-Denk bodies (MBD), described in alcoholic hepatitis, are composed of intermediate filaments admixed with other proteins. These cytoplasmic inclusions are irregularly shaped and eosinophilic as seen under the light microscope. MBD-like inclusions have rarely been described outside the hepatobiliary tree. Though rare, intracytoplasmic inclusions have been reported in ovarian fibromas. This study evaluates a series of torsed ovarian fibromas with intracytoplasmic inclusions resembling MDBs. Forty-three ovarian fibromas were retrieved from the pathology archives. The H&E slides were evaluated for the presence of MBD-like inclusions and histologic evidence of torsion. The cases with histologic features of torsion were included in the study group while the nontorsed fibromas formed the control group. Among the 15 cases of fibromas with torsion, MBD-like intracytoplasmic inclusions were seen in 5 cases, predominantly in the interface between necrotic areas and viable stroma. None of the cases from the control group showed any inclusions. There was no significant difference in the size of the fibroma or patient demographics between cases with and without inclusions. The inclusions were positive for cytokeratin and ubiquitin while being negative for per acidic Schiff and periodic acid-Schiff with diastase reaction, in the 3 cases selected for immunohistochemistry and special stains. Electron microscopy of the index case revealed a predominance of type 3 Mallory hyaline. This is the first report describing MDB-like inclusions in ovarian fibromas. These MDB-like inclusions appear to be limited to a fraction of ovarian fibromas that underwent torsion, suggesting that these inclusions likely result from subacute hypoxic damage to the cells.
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Yolk sac differentiation occurs in somatic neoplasms of the gastrointestinal and gynecologic tracts; it has rarely been reported in urothelial carcinoma. Here, we report three cases of yolk sac differentiation in sarcomatoid urothelial carcinoma. The epithelioid component of the sarcomatoid urothelial carcinoma showed divergent differentiation, including squamous, conventional glandular, small cell carcinoma, and yolk sac components. The sarcomatoid component showed malignant spindle cells admixed with focal chondroid and rhabdoid elements. In all three cases, the yolk sac areas were admixed with the sarcomatoid component and showed a glandular pattern, with vacuolated, eosinophilic cytoplasm. These areas were positive for SALL4, variably positive for glypican 3 and AFP, and negative for the conventional urothelial markers GATA3, p63, and 34ßE12. Yolk sac differentiation is an extremely rare occurrence in sarcomatoid urothelial carcinoma.
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Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Biomarcadores Tumorais , Carcinoma de Células de Transição/diagnóstico , Carcinoma de Células de Transição/patologia , Feminino , Humanos , Neoplasias da Bexiga Urinária/patologia , Urotélio/patologia , Saco Vitelino/patologiaRESUMO
ABSTRACT: Cutaneous malignant melanoma is an aggressive cancer that contributes significantly to cancer-related mortality. Over the years, a deeper scrutiny of melanoma biology has led to identification of diverse evolutionary patterns involving various genetic pathways. This study attempts to further understand the genetic landscape of cutaneous malignant melanoma in terms of loco-regional variations and malignant potential. Thirty-five cases of cutaneous malignant melanoma were retrieved from the archives and were classified based on location of the primary tumor and presence or absence of metastatic disease. Next-generation sequencing data consisting of base substitutions, copy number variations, indels, and rearrangements in a total of 324 genes were analyzed for recurrent genetic alterations. Statistical analysis was performed using IBM SPSS26 software. Mutations in KDM gene family were found in 62.5% of the melanomas in the head and neck as compared with 10% in melanomas of the extremity and trunk (P = 0.03). Mutations in the RAS gene family were found in 70% of melanomas in the extremities as compared to 12.5% in melanomas of the head and neck (P = 0.003). BTK gene mutations were found exclusively in melanomas of the head and neck (P = 0.032). CREBBP mutations were seen in 50% of the nonmetastatic melanomas as compared with 3.57% of metastatic melanomas (P = 0.005). This study highlights the loco-regional variations in cutaneous malignant melanoma for genetic alterations involving the KDM, RAS, and BTK gene family. In addition, the CREBBP mutational status is identified as a potential prognostic marker for predicting metastatic potential in cutaneous malignant melanomas.
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Biomarcadores Tumorais/genética , Melanoma/patologia , Neoplasias Cutâneas/patologia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Melanoma Maligno CutâneoRESUMO
Bronchiolar adenomas (BAs)/ciliated muco-nodular papillary tumors (CMPTs), are small, peripheral lung nodules arising predominantly in the elderly that follow a benign course. They can be mistaken for adenocarcinomas on frozen section. Immunohistochemistry (IHC) for basal cell markers highlights the continuous layer of basal cells underlying the tumor cells in BAs. BAs are further subdivided into proximal-type and distal type. Six BAs were retrieved from the pathology archives. The cases were classified based on morphology into proximal and distal BAs. The clinical and radiological features were reviewed. Immunohistochemistry and special stains were performed. The most common radiological picture of BA/CMPT was of a solid nodule with SUVmax < 3 as seen in 60% cases. 40% cases showed cavitation on CT. On histological examination, four cases were morphologically classified as proximal BAs and two as distal BAs. In proximal BAs, TTF1 was focally positive only in the basal cells in three of four. The mucin stained acidic. In distal BAs, TTF1 was diffusely positive in both basal and luminal cells. There was scant intracellular neutral mucin. Both the distal BAs had concomitant neuroendocrine tumors in the same lobe. Though the number of cases evaluated in this study is too low to be statistically significant, this study provides additional evidence to the concept of BA classification based on site specific histology and supplementary immunohistochemistry and reiterates the radiological features that may help distinguish it from malignant lesions.
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Adenoma , Brônquios/patologia , Adenocarcinoma/diagnóstico , Adenocarcinoma/patologia , Adenoma/classificação , Adenoma/diagnóstico , Adenoma/diagnóstico por imagem , Adenoma/patologia , Idoso , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/metabolismo , Carcinoma Papilar/diagnóstico , Carcinoma Papilar/patologia , Proteínas de Ligação a DNA/análise , Proteínas de Ligação a DNA/metabolismo , Diagnóstico Diferencial , Feminino , Humanos , Imuno-Histoquímica , Neoplasias Pulmonares/classificação , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Masculino , Mucinas/análise , Mucinas/metabolismo , Radiografia , Fatores de Transcrição/análise , Fatores de Transcrição/metabolismoRESUMO
BACKGROUND: Adenomyomatous hyperplasia (AMH) of the gallbladder, reported in 1-8.7% of cholecystectomies, consists of cystically dilated sinuses/glands with a surrounding spindle cell proliferation which is thought to be composed of smooth muscle cells. Myofibroblasts are contractile cells that secrete a variety of biochemical modulators causing a "field-effect". Myofibroblasts can be immunohistochemically distinguished from smooth muscle cells by their desmin negativity. METHODS: Eighteen cases of AMH and five cases each of chronic follicular cholecystitis, chronic cholecystitis, gallbladder carcinoma and 10 colonic diverticular disease were stained with actin and desmin. The percentage of myofibroblasts was estimated by the difference between actin and desmin staining in the same field. Statistical anlysis was performed using SPSS 22.0. RESULTS: The percentage of actin staining was significantly higher in AMH and gallbladder carcinoma compared to chronic follicular and chronic cholecystitis (p = 0.04). The percentage of desmin staining did not show any significant difference between the four groups. The estimated myofibroblastic population was significantly higher in AMH when compared to chronic follicular and chronic cholecystitis (p = 0.005). CONCLUSION: The spindle cell proliferation around cystically dilated glands in AMH is composed predominantly of myofibroblasts and of smooth muscle cells as previously described. This finding suggest a derangement in epithelial-stromal interactions as the underlying pathophysiology in AMH.
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Neoplasias da Vesícula Biliar , Actinas , Neoplasias da Vesícula Biliar/cirurgia , Humanos , HiperplasiaRESUMO
Primary sebaceous carcinoma of the breast is an exceedingly uncommon neoplasm that is defined as primary invasive carcinoma of the breast with sebaceous differentiation in more than 50% of cells. All confirmed cases have been reported in women. Herein, we report the case of a 70-year-old man with a primary sebaceous breast carcinoma, the first unequivocal case to be reported thus far in a man.
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Neoplasias da Mama , Carcinoma , Idoso , Feminino , Humanos , Masculino , SíndromeRESUMO
In modern medicine, there is an increasing dependence on noninvasive imaging modalities, for diagnosis and management of diseases. Though there are definite advantages to this, they are at times offset by diagnostic pitfalls especially in entities with elusive clinical presentation.Peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS) is an aggressive subtype of T-cell lymphomas that does not meet criteria for a specific subtype. Peripheral T-cell lymphoma usually has varied clinical presentations depending on the site of involvement. Vast majority of PTCL patients present with systemic disease, generalized lymphadenopathy and constitutional symptoms. Pulmonary involvement is relatively rare and is seen in approximately 10% of patients.Here in we highlight a rare case of PTCL, masquerading as pneumonia due to extensive pulmonary involvement that went undiagnosed and was discovered at autopsy. This case of malignant lymphoma of T-cell origin involving the lung, which is very rare, highlights the continued importance of medical autopsies not only as a teaching tool but also as an important adjunct to investigative medicine in uncovering lapses that can subsequently be avoided to improve patient care and decrease mortality.
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Broncopneumonia/diagnóstico por imagem , Linfoma de Células T Periférico/diagnóstico , Idoso , Broncopneumonia/etiologia , Erros de Diagnóstico , Exantema/patologia , Febre/etiologia , Humanos , Pulmão/diagnóstico por imagem , Pulmão/patologia , Masculino , Tomografia Computadorizada por Raios XRESUMO
Background: Tracheal agenesis/atresia (TA) presents with respiratory distress at birth and subsequent difficulty in endotracheal intubation. The antenatal course is complicated by polyhydramnios and premature labor. Case report: We present a newborn baby boy with respiratory distress and unsuccessful intubation. Postmortem neck dissection revealed tracheal atresia with esophageal atresia and high tracheoesophageal fistula. Conclusion: In this variant of tracheal atresia, the coexistent esophageal atresia precluded the establishment of a functional air passage. This variant that does not fall into the any of the described categories in accepted classification systems. The lack of any distal communication makes this case inoperable and fatal.
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Anormalidades Múltiplas/genética , Constrição Patológica/genética , Atresia Esofágica/genética , Traqueia/anormalidades , Fístula Traqueoesofágica/genética , Anormalidades Múltiplas/diagnóstico , Autopsia/métodos , Constrição Patológica/complicações , Constrição Patológica/diagnóstico , Atresia Esofágica/complicações , Atresia Esofágica/diagnóstico , Feminino , Humanos , Recém-Nascido , Intubação/métodos , Gravidez , Fístula Traqueoesofágica/diagnósticoRESUMO
Lung cancer has very high mortality due to late stage diagnosis not amenable to curative resection. Cancer specific methylation patterns of tumor suppressor genes may precede precursor lesions of lung cancer. Our aim was to evaluate the promoter hypermethylation of tumor suppressor gene NISCH and CDH1 in cfDNA from plasma of lung cancer patients and its possible correlation with smoking status and various clinicopathological parameters. Forty histopathologically confirmed lung cancer cases, thirty smoker and thirty nonsmoker controls were enrolled. Plasma cfDNA was extracted and subjected to bisulfite treatment followed by MS-PCR. Serum nischarin levels were estimated by ELISA. The frequency of promoter hypermethylation of NISCH and CDH1 was significantly higher in lung cancer patients as compared to lifelong non-smoker controls (p < 0.05). It did not vary with smoking status among cancer cases. No significant association was found with staging or histological grading. NISCH methylation was found to be significantly higher among smoker controls. Pack years and packs per day were significantly higher in the methylated group. Serum nischarin levels showed no significant association with NISCH methylation or clinicopathological variables. NISCH is highly methylated in both high risk smoker controls as well as cancerousnon-smokers and may mark the convergence of varied etiologies of lung cancer. Hence NISCH and CDH1 are highly methylated in plasma cfDNA of lung cancer patients.
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Hiperplasia do Linfonodo Gigante/complicações , Linfoma de Efusão Primária/complicações , Linfoma de Efusão Primária/diagnóstico , Tálamo/patologia , Biópsia , Hiperplasia do Linfonodo Gigante/patologia , Infecções por Herpesviridae/complicações , Infecções por Herpesviridae/patologia , Herpesvirus Humano 8/isolamento & purificação , Humanos , Linfoma de Efusão Primária/patologia , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVES: The BCR::ABL1 negative myeloproliferative neoplasms are sequentially tested for JAK2 p.V617F, followed by CALR exon 9 pathogenic variants. Historically, these variants were thought to be mutually exclusive. However, recent reports indicate coexisting JAK2 p.V617F and CALR exon 9 somatic variants. METHODS: Analysis of JAK2 p.V617F and CALR exon 9 variant was performed by polymerase chain reaction (PCR)-based assays. Subsequent testing was performed on the Genexus integrated sequencer (ThermoFisher) using the Oncomine myeloid assay GX v2. RESULTS: CALR exon 9 variants were positive in 3 cases, while 2 were positive for JAK2 p.V617F on PCR-based assays. Next-generation sequencing confirmed the JAK2 P.V617F status in all cases. CALR variants resulting in in-frame deletions were identified in 2 cases at a variant allele frequency of 52.16% and 50.91%, while the third case had an intronic CALR variant c.-48G>A at a variant allele frequency of 51.1%. Thus, CALR variants in all 3 cases were interpreted as potentially germline. Of the 228 cases that underwent JAK2 p.V617F and CALR cotesting in the past 2 years, only these 2 cases were positive for both JAK2 p.V617F and CALR exon 9 variants. CONCLUSIONS: These cases highlight the importance of understanding the pitfalls of molecular techniques in current practice.
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Transtornos Mieloproliferativos , Neoplasias , Humanos , Calreticulina/genética , Calreticulina/metabolismo , Transtornos Mieloproliferativos/diagnóstico , Transtornos Mieloproliferativos/genética , Mutação , Éxons/genética , Janus Quinase 2/genética , Janus Quinase 2/metabolismo , Reação em Cadeia da PolimeraseRESUMO
Ocular hemorrhage has been recorded in congenital factor deficiencies like hemophilia A, but it has never been documented in prothrombin deficiency. Here, we describe an unusual case of sudden vision loss in the right eye caused by subretinal hemorrhage following a coughing episode in a 67-year-old woman. Notably, the patient underwent left eye enucleation 12 years previously under similar circumstances due to subretinal hemorrhage. During the interview, it was discovered that the patient had a history of prothrombin deficiency, which was subsequently confirmed through laboratory testing. Aside from recurrent ocular bleeding and 1 instance of bleeding following dental extraction in childhood, there is no other history of bleeding. Subsequent molecular studies revealed a homozygous missense mutation at G1499A (Arg500Gln), a variant previously identified as R457Q. Although the likelihood of prothrombin deficiency initiating subretinal hemorrhage is low, it is likely to worsen retinal hemorrhage and contribute to difficulty in controlling bleeding. A comprehensive coagulation workup is essential in patients with ocular hemorrhage. Determining factor II activity should be included in individuals exhibiting variably prolonged prothrombin time and activated partial thromboplastin time with correction in mixing studies. Additional investigations, such as genetic sequencing and family studies, are advised for those with isolated low prothrombin levels.
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OBJECTIVES: Myeloid neoplasms require comprehensive characterization of genetic abnormalities, including single-nucleotide variants, small insertions and deletions, and fusions and translocations for management. The Oncomine Myeloid Assay GX v2 (Thermo Fisher Scientific) analyzes 17 full genes, 28 hotspot genes, 30 fusion driver genes, and 5 expression genes. METHODS: The validation set included 192 DNA samples, 28 RNA samples, and 9 cell lines and contrived controls. The DNA and RNA were extracted from both peripheral blood and bone marrow. Library preparation, templating, and sequencing was performed on the fully automated Genexus Integrated Sequencer (Thermo Fisher Scientific). The sequencing data were analyzed by manual curation, default Oncomine filters and the Oncomine Reporter (Thermo Fisher Scientific). RESULTS: Of the 600 reference pathogenic DNA variants targeted by the assay, concordance was seen in 98.3% of unfiltered variant call format files. Precision and reproducibility were 100%, and the lower limit of detection was 2% variant allele frequency for DNA. Inability to detect variants in long homopolymer regions intrinsic to the Ion Torrent chemistry led to 7 missed variants; 100% concordance was seen with reference RNA samples. CONCLUSIONS: This extensive clinical validation of the Oncomine Myeloid Assay GX v2 on the Genexus Integrated Sequencer with its built-in bioinformatics pipeline and Ion Torrent Oncomine Reporter shows robust performance in terms of variant calling accuracy, precision, and reproducibility, with the advantage of a rapid turnaround time of 2 days. The greatest limitation is the inability to detect variants in long homopolymer regions.
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OBJECTIVES: Adult T-cell leukemia/lymphoma (ATLL) is an aggressive mature T-cell neoplasm caused by human T-cell lymphotropic virus type 1 (HTLV-1). Its most common immunophenotype is CD4+/CD7-/CD25+, although unusual immunophenotypes can occur and may lead to misdiagnosis. METHODS: The immunophenotypes, cytogenetics, molecular features, clinical presentations, treatment, and prognosis of 131 patients with ATLL were retrospectively studied in a large tertiary medical center in the United States. RESULTS: All cases showed loss of CD7 expression. While 82.4% of cases demonstrated CD4+, 17.6% exhibited unusual phenotypes, including CD4+/CD8+ (6.9%), CD4-/CD8- (2.3%), CD5- (3.1%), CD2-, and CD3-. The most common cytogenetics abnormalities included polysomy 3 (34.6%), translocation 1 (23.1%), and abnormalities found on chromosome 11 (30.8%) and chromosome 14 (26.9%). The common gene mutations identified by the next-generation sequencing study were TP53 (16.7%), TBL1XR1 (16.7%), EP300 (14.3%), and NOTCH1 (14.3%). TBL1XR1 mutation is associated with genetic instabilities. There was no significant difference between the clinical presentations of these 2 groups. CONCLUSIONS: Adult T-cell leukemia/lymphoma exhibits versatile immunophenotypic, cytogenetic, and molecular features. Simultaneous involvement of blood, lymph nodes, and other organs, along with hypercalcemia in a patient from an endemic area, necessitates HTLV-1 testing to avoid underdiagnosis of this dismal disease that might need aggressive chemotherapy followed by bone marrow transplant.
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Acute promyelocytic leukemia (APL) is characterized by the pathogenic driver fusion transcript PML-RARA resulting from the t(15;17) translocation. Early recognition of APL with prompt ATRA induction has a decisive impact on the early death rate. The preliminary diagnosis of APL relies heavily on cytomorphology and flow cytometry. In APL with variant morphology, such as the microgranular variant, immunophenotype, especially the bright MPO positivity is the basis of diagnosis. Till date, only five cases of APL with reduced/absent MPO have been described in literature. The identification of MPO deficiency based on genetic testing would involve at the least a MPO gene scanning with NGS, followed by microarray to identify somatic uniparental disomy in heterozygotes. This testing is not only redundant given the scant clinical implications of heterozygous MPO deficiency but also time consuming. An easy way to identify background MPO deficiency confounding the immunophenotype of a myeloid neoplasm is the MPO expression in background neutrophils gated on the initial flow cytometry. A dim MPO in the background neutrophils, in the morphological setting of APL, can identify underlying MPO deficiency, clarifying the immunophenotypic ambiguity and thus establishing an unequivocal diagnosis as seen in the current case.
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Leiomyoadenomatoid tumors of the epididymis are exceedingly rare biphasic tumors composed of an adenomatoid component in the form of gland-like structures lined by single flat or cuboidal cells admixed with smooth muscle. Radiological and gross findings cannot distinguish leiomyoadenomatoid tumors from the more common classic adenomatoid tumors or leiomyomas, and careful microscopic examination is critical in the identification of this esoteric variant. The histogenesis of this entity remains ambiguous. Common hypotheses include a collision tumor, a variant of an adenomatoid tumor with a smooth muscle component, or an adenomatoid tumor arising in the background of reactive smooth muscle hyperplasia. We present 2 cases of leiomyoadenomatoid tumors with diffuse nuclear WT1 positivity in both the adenomatoid and smooth muscle components, supporting the mesothelial origin of these tumors.
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Adenoma , Tumor Adenomatoide , Leiomioma , Masculino , Humanos , Tumor Adenomatoide/patologia , Leiomioma/diagnóstico , Epididimo/patologia , Músculo Liso/patologia , Proteínas WT1RESUMO
Objectives: The aim of this study is to analyze the prevalence of somatic mutations in BRCA1 and BRCA2 in malignant mesothelioma and their putative impact on protein properties. Methods: Eighteen cases of malignant mesothelioma were retrieved from the archives and for next generation sequencing analysis of BRCA1 and BRCA2 genes. Variants were analyzed using Ensembl VEP17, Polyphen 2.0 software, SIFT software, MutpredV2, and SWISS-MODEL homology-modeling pipeline server. Results: BRCA2 variants were found in significantly higher percentage (22%) of cases (p=0.02). Five missense variants were identified. These were p.A2351P, p.T2250A, p.A895V, pG1771D, and p.R2034C. The SIFT scores of all except one were ≥ 0.03. The Polyphen scores of these four alterations were ≤0.899. In case of p.A2315, the SIFT score was 0.01, while the Polyphen 2 score was 0.921. MutPred2 scores were ≤0.180 for all. Loss of intrinsic disorder was predicted (Pr=0.32, p=0.07) for p.R2034C, while gain of intrinsic disorder was predicted for p.A2351P (Pr=0.36, p=0.01) and p.G1771D (Pr=0.34, p=0.02). Conclusions: BRCA2 somatic variants were identified in 22% cases of malignant mesotheliomas in this study. The variants localize more frequently to the disordered regions of the protein and are predicted to affect the level of disorder.
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PIK3CA-related overgrowth spectrum (PROS) is a heterogeneous group of diseases, with varied clinical presentations ranging from isolated segmental overgrowths to megalencephaly and vascular malformations, all resulting from post-zygotic activating mutations in PIK3CA. Isolated macrodactyly of upper limb is extremely rare, accounting only for 0.9%-1% of all congenital anomalies of the upper limb. This report describes a case of congenital, isolated, nonprogressive macrodactyly of the right index finger and thumb, in an adult patient that was treated with debulking surgery. The microscopic features were compatible with lipomatosis of nerve. Due to the prompt and pertinent molecular testing, which identified a somatic PIK3CA variant, c.3140A > G, p.H1047R., the case was classified as a PROS. The availability of mTOR inhibitors offers additional treatment possibilities in cases with progressive disease. This case report highlights the importance of molecular testing to identify PROS, to further the knowledge of this continually expanding entity.
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BACKGROUND: Breast cancer, one of the leading causes of cancer-related mortality in women worldwide, exhibits wide-ranging histo-morphologic, clinical and molecular diversity. OBJECTIVE: This study compares the genetic alterations of breast tumors with the histo-morphological, hormone receptor status and metastatic "organotropism". MATERIALS AND METHODS: Twenty-two cases of primary invasive breast carcinoma with local/distant metastasis were retrieved from the pathology archives. The status of estrogen and progesterone receptors by immunohistochemistry was recorded along with other pertinent case data. Next generation sequencing was performed on formalin-fixed paraffin embedded blocks of tumor. RESULTS: The mean age of the study subjects was 57.9 ± 13.3 years. TP53 mutation was the most common gene alteration in this study and was seen in 40.9% cases. ROS1 gene was mutated in 44.4% PR negative breast cancers while being wild type in the twelve PR positive tumors. (p = 0.021).STRING interaction network constructed with ROS1 and PR revealed a significantly higher number of interactions in this network than expected (p-value 0.000973). CONCLUSION: This study highlights the significantly higher incidence of ROS1 gene alterations in metastatic PR- breast cancers, with STRING network analysis revealing higher nodal interaction in the nodal network comprised of PR and ROS1 exclusive of ER.
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Neoplasias da Mama , Adulto , Idoso , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Feminino , Humanos , Pessoa de Meia-Idade , Proteínas Tirosina Quinases , Proteínas Proto-Oncogênicas , Receptor ErbB-2/genética , Receptores de Estrogênio/genética , Receptores de Progesterona/genéticaRESUMO
PURPOSE: The gastrointestinal tract is home to a wide variety of neoplasms. Gastrointestinal adenocarcinomas display distinct prognostic patterns. With the advent of next generation sequencing, attempts are being made to delineate distinct molecular characteristics of these adenocarcinomas from adjoining anatomical sites. METHODS: Thirty-seven cases of upper gastrointestinal adenocarcinomas including those of the esophagus, gastroesophageal junction, stomach, small intestine and gallbladder were retrieved. Next generation sequencing data consisting of base substitutions, copy number variations, indels and rearrangements, in 324 genes, were analyzed for recurrent genetic abnormalities. Statistical analysis was performed using IBM SPSS25 and SAS software. RESULTS: Genetic alterations were found in 181 genes. APC mutations were found in 50% of the esophageal adenocarcinomas, 5% of the gastric adenocarcinomas and 33.3% of the small intestinal adenocarcinomas (p = 0.04). PIK3 gene family mutations were found in 10% of the gastric adenocarcinomas, 66% of the gall bladder adenocarcinomas and 66% of the small intestinal adenocarcinomas (p = 0.002). The mutations were found exclusively in the PIK3 class 1 family. TP53 mutations were more common in tumors with intact DNA mismatch repair protein expression as assessed by immunohistochemistry (p = 0.042). CONCLUSION: In this study, APC gene mutations were found to be more frequent in esophageal and small intestinal adenocarcinomas than previously reported. PIK3 class 1 gene family mutations were found to be more frequent in gallbladder and small intestinal adenocarcinomas. An inverse relationship was found between TP53 mutations and loss of DNA mismatch repair protein expression.