Distinct Histopathological Features Research Articles

Left-sided colorectal cancer distinct in indigenous African patients compared to other ethnic groups in South Africa

IntroductionA large proportion of indigenous African (IA) colorectal cancer (CRC) patients in South Africa are young (< 50 years), with no unique histopathological or molecular characteristics. Anatomical site as well as microsatellite instability (MSI) status have shown to be associated with different clinicopathological and molecular features. This study aimed to ascertain key histopathological features in microsatellite stable (MSS) and low-frequency MSI (MSI-L) patients, to provide insight into the mechanism of the disease.MethodsA retrospective cohort (2011–2015) of MSS/MSI-L CRC patient samples diagnosed at Charlotte Maxeke Johannesburg Academic Hospital was analyzed. Samples were categorized by site [right colon cancer (RCC) versus left (LCC)], ethnicity [IA versus other ethnic groups (OEG)] and MSI status (MSI-L vs MSS). T-test, Fischer’s exact and Chi-square tests were conducted.ResultsIA patients with LCC demonstrated an increased prevalence in males, sigmoid colon, signet-ring-cell morphology, MSI-L with BAT25/26 marker instability and advanced disease association.ConclusionThis study revealed distinct histopathological features for LCC, and suggests BAT25 and BAT26 as negative prognostic markers in African CRC patients. Larger confirmatory studies are recommended.

Correlation of Immunological and Histopathological Features with Gene Expression-Based Classifiers in Colon Cancer Patients.

The purpose of this study was to evaluate the association between four distinct histopathological features: (1) tumor infiltrating lymphocytes, (2) mucinous differentiation, (3) tumor-stroma ratio, plus (4) tumor budding and two gene expression-based classifiers—(1) consensus molecular subtypes (CMS) plus (2) colorectal cancer intrinsic subtypes (CRIS). All four histopathological features were retrospectively scored on hematoxylin and eosin sections of the most invasive part of the primary tumor in 218 stage II and III colon cancer patients from two independent cohorts (AMC-AJCC-90 and AC-ICAM). RNA-based CMS and CRIS assignments were independently obtained for all patients. Contingency tables were constructed and a χ2 test was used to test for statistical significance. Odds ratios with 95% confidence intervals were calculated. The presence of tumor infiltrating lymphocytes and a mucinous phenotype (>50% mucinous surface area) were strongly correlated with CMS1 (p < 0.001 and p = 0.008) and CRIS-A (p = 0.006 and p < 0.001). The presence of mucus (≥ 10%) was associated with CMS3: mucus was present in 64.1% of all CMS3 tumors (p < 0.001). Although a clear association between tumor-stroma ratio and CMS4 was established in this study (p = 0.006), still 32 out of 61 (52.5%) CMS4 tumors were scored as stroma-low, indicating that CMS4 tumors cannot be identified solely based on stromal content. Higher budding counts were seen in CMS4 and CRIS-B tumors (p = 0.045 and p = 0.046). No other associations of the measured parameters were seen for any of the other CRIS subtypes. Our analysis revealed clear associations between histopathologic features and CMS or CRIS subtypes. However, identification of distinct molecular subtypes solely based on histopathology proved to be infeasible. Combining both molecular and morphologic features could potentially improve patient stratification.

S2024 Elderly Patient, Youthful Pathology: Solitary Colonic Juvenile Polyp Found in a 75-Year-Old Male

Introduction: Colonic juvenile polyps are generally found in the pediatric population. Classically, juvenile polyps (JP) are the most common polyp subtype seen in pediatric gastroenterology, accounting for approximately 80-90% of polyps in children. Generally, JP are diagnosed within the first decade of life and most common presentation is painless rectal bleeding. Other terminology used are juvenile hamartomatous polyp or retention polyps. There is no malignant potential for solitary JP and they tend to not recur. Case Description/Methods: We present a 75-year-old male with past medical history of hypertension, diabetes and hyperlipidemia referred to gastroenterology for surveillance colonoscopy due to a history of tubular adenomas. At the pre-procedure visit, the patient was well without GI complaints such as overt bleeding, change in bowel habits or unintentional weight loss. No family history of colon cancer or polyps was reported. Physical exam and vitals were normal at the time of procedure. Colonoscopy revealed a 40mm pedunculated sigmoid colon polyp which was excised using an endoloop at the stalk base followed by hot snare polypectomy ((Figure A). Three other sub-centimeter sessile polyps in the rectosigmoid area were removed by cold snare polypectomy. Histopathological examination of the large pedunculated polyp was consistent with a JP(Figure B). Other polyps were tubular adenomas. Discussion: Our current patient is the oldest reported case of isolated colonic JP. These polyps tend to have a common phenotypical appearance measuring around 10-30mm and roughly 90% of them are considered pedunculated. JP are ultimately defined by their distinctive histopathological features such as edematous lamina propria with inflammatory cells, cystically dilated glands that are bordered by cuboidal or columnar epithelium with reactive changes, and mucus filled glands. Fortunately for our patient, the presence of only a solitary colonic JP generally carries no known malignant potential. Juvenile polyposis syndrome (JPS) on the other hand is a hereditary condition characterized by the presence of hamartomatous polyps in the digestive tract and is known to have an increased risk of digestive tract malignancies. JPS is suspected when a patient has 5 or more juvenile polyps in the gastrointestinal tract or a juvenile polyp and a family history of juvenile polyps. A DNA test to check SMAD4 or BMPR1A gene is helpful.Figure 1.: (a) A 40mm polyp (Paris 0-Ip) located in the in the sigmoid colon. (b) Hamartomatous polyp has ulcerated surface with benign dilated glands.

S2061 Looks Aren't Everything: A Rare Case of Metastatic Colonic Neuroendocrine Tumor

Introduction: Gastrointestinal neuroendocrine tumors (NETs) are rare, slow growing tumors with distinct histopathological characteristics. Endoscopically, they appear as sessile, flat polypoid lesions, making them difficult to distinguish from pathologically benign polyps. They can be found anywhere within the gastrointestinal tract with the terminal ileum being the most common location. Severity of disease varies based on size, macroscopic ulcerations, and hyperemia of mucosal surfaces. NETs of the colon and rectum are extremely rare and account for only 1% of all colorectal malignancies. Patients typically remain asymptomatic until the tumor is large enough to cause obstruction or abdominal pain and is diagnosed during routine colonoscopy. Case Description/Methods: We present a 63-year-old male with a past medical history of hypertension, hyperlipidemia, and parathyroidectomy, who on colonoscopy in 2019 had 3 benign-appearing polyps showing mixed hyperplastic and tubular adenoma morphology. Three years later, repeat colonoscopy revealed 5 sessile polyps of varying sizes from 2 mm to 6 mm, where all were completely resected. Pathology showed 4 tubular adenomas and a 2-millimeter low grade (WHO 2010 Grade 1) well-differentiated neuroendocrine tumor located in the sigmoid colon. The latter exhibited typical findings of NETs with a trabecular growth pattern, round nuclei, and a “salt and pepper” chromatin. Ki-67 proliferative index was 1%. Tumor cells were positive for synaptophysin, and chromogranin, and negative for CK7, CK20 and CDX2. PET scan demonstrated intensely DOTATATE avid mural thickening at the duodenal bulb and proximal second portion of the duodenum, along with uptake in liver, and pulmonary nodules, with osseous lesions suspicious for metastatic disease. Repeat colonoscopy 2 months later was unrevealing without evidence of neuroendocrine tumor (Figure 1). Discussion: Colorectal NETs are rapidly progressive with a poor prognosis compared to colorectal adenocarcinoma. Our case demonstrates that low grade, well differentiated NETs of the colon can undergo rapid high-grade transformation within a short interval between colonoscopies. When considering NETs without known metastatic disease, lesions that are amenable to endoscopic resection may be treated with endoscopic intervention and surveillance alone. Given rapid progression of disease and predilection for metastasis, our case highlights the need for early detection of NETs with interval screening colonoscopies to decrease morbidity and mortality.Figure 1.: Image A: 3 mm polyp located in the sigmoid colon. Appears sessile and flat with no malignant appearing lesion. Image B: 2 polyps located in the transverse colon, 3 mm and 5 mm in size, which endoscopically appear similar to image A. Pathology is consistent with tubular adenoma.

Histopathological study of scalp tumors and tumor like lesions

Introduction: A variety of inflammatory and neoplastic scalp lesions is encountered in clinical practice, which can be attributed to trauma, infection, abscess, allergic reaction, or tumor. Though a majority of scalp involvement is by benign processes, still it can be a site of malignant neoplasm.Aims and objectives 1.To study the morphological, histopathological types and clinico-pathological correlation of various scalp tumors.2.To know the proportion of benign and malignant lesions in the scalp lesions.3.To compare the data and other investigations with similar studies from other regions.Materials and methods: The present retrospective study is conducted in the department of pathology, B.J. Medical college and civil hospital, Ahmedabad over a duration of 5 years. A total of 105 cases of scalp lesions were evaluated. Scalp biopsies with clinical suspicion of a tumor which presented with a swelling, with or without pain or with non-healing ulcer were included in the study. The spectrum of lesions that appeared in the scalp were tabulated. Results: In our study, total 105 cases were observed during period of five years. Out of the total of 105 cases majority of them were benign accounting for 92.38% of all cases and malignant cases accounting for 7.62% of all cases. The sex distribution of scalp lesions in the present study was slightly greater in male accounting for 60% cases. Out of 105 cases majority are non-tumorous keratinous cysts accounting for 53.3% of all cases with trichilemmal cyst being most common. Conclusion: Benign tumors and tumor like lesions are more common than malignant tumors. Although mostly benign diagnosis and treatment of these lesions pose significant challenge due to distinct histopathological features. A high index of clinical suspicion is essential to ensure early detection of malignancies and initiate treatment.

Inclusion body myositis: Update on the diagnostic and therapeutic landscape.

Inclusion body myositis (IBM) is a progressive muscle disease affecting patients over the age of 40, with distinctive clinical and histopathological features. The typical clinical phenotype is characterized by prominent involvement of deep finger flexors and quadriceps muscles. Less common presentations include isolated dysphagia, asymptomatic hyper-CKemia, and axial or limb weakness beyond the typical pattern. IBM is associated with marked morbidity as majority of patients eventually become wheelchair dependent with limited use of their hands and marked dysphagia. Furthermore, IBM mildly affects longevity with aspiration pneumonia and respiratory complications being the most common cause of death. On muscle biopsy, IBM is characterized by a peculiar combination of endomysial inflammation, rimmed vacuoles, and protein aggregation. These histopathological features are reflective of the complexity of underlying disease mechanisms. No pharmacological treatment is yet available for IBM. Monitoring for swallowing and respiratory complications, exercise, and addressing mobility issues are the mainstay of management. Further research is needed to better understand disease pathogenesis and identify novel therapeutic targets.

Chemopreventive Properties of Black Raspberries and Strawberries in Esophageal Cancer Review.

Esophageal cancer is one of the most fetal malignancies in the world. Esophageal squamous cell carcinoma (SCC) and esophageal adenocarcinoma (AC) are two main types of esophageal cancer and each with distinct epidemiological, etiological and histopathological characteristics. The continued global prevalence of tobacco use and alcohol consumption, coupled with limited intake of fresh fruits and vegetables, ensures that esophageal cancer will remain one of the major health threats. In addition to promoting quitting smoking and alcohol abuse, one of the strategies of cancer prevention is to identify foods, food components, or dietary patterns that can prevent or delay the onset of esophageal cancer. A food-based approach has the advantage of a complex of mixtures of bioactive components simultaneously targeting multiple processes in carcinogenesis. We have employed a preclinical rodent model of esophageal SCC to assess the effects of black raspberries (BRB) and strawberries. Our investigations demonstrate that BRB and strawberries are potent inhibitors of esophageal cancer. To prepare for this review, a literature search was performed to screen BRB and strawberries against esophageal cancer using electronic databases from PubMed, Science Direct and Google Scholar. Search was conducted covering the period from January 2000 to June 2022. Our present review has provided a systematic review about chemopreventive effects of BRB and strawberries in esophageal cancer by collecting and compiling diverse research findings from the above sources. In this review, we discussed the anti-tumor potentials of BRB and strawberries in esophageal SCC and esophageal AC separately. For each cancer type, we discuss animal models and research findings from both animal bioassays and human clinical studies. We also discuss the potential mechanisms of action of berries and their key bioactive components.

Mucinous carcinoma of the breast: distinctive histopathologic and genetic characteristics

Mucinous carcinoma is a rare histologic type of breast cancer that, when classified with favorable histology, can be treated with different therapeutic options. This study reviews the histologic findings of mucinous carcinoma that support or exclude favorable histology and emphasizes the necessity of an appropriate gross examination with radiologic findings for an accurate diagnosis. In addition, unusual findings such as micropapillary arrangements and lobular differentiation in mucinous carcinoma and their implications for prognosis and treatment are reviewed. Mucinous carcinoma involves upregulation of MUC2, a mucus-associated gene common in mucinous carcinoma of the breast as well as various other organs. In mucinous carcinoma, the fraction of genome altered and tumor mutation burden are lower than those of invasive carcinoma of no special type, the most common histology of breast cancer. In addition, the genetic alterations found in mucinous carcinoma are diverse, unlike the pathognomonic genetic alterations observed in other histologic types of breast cancer. These genetic features support the importance of conventional microscopic evaluations for the pathologic differential diagnosis of mucinous carcinoma of the breast in routine practice. A variety of breast lesions, including mucinous cystadenocarcinoma and mucocele-like lesions, as well as mucinous carcinoma from other organs, can mimic mucinous carcinoma of the breast. In order to obtain an accurate pathologic diagnosis, careful evaluation of the overall histopathologic characteristics and ancillary testing are required to provide information on appropriate treatment and prognosis.

Sporadic Creutzfeldt-Jakob disease VM1: phenotypic and molecular characterization of a novel subtype of human prion disease

The methionine (M)—valine (V) polymorphic codon 129 of the prion protein gene (PRNP) plays a central role in both susceptibility and phenotypic expression of sporadic Creutzfeldt-Jakob diseases (sCJD). Experimental transmissions of sCJD in humanized transgenic mice led to the isolation of five prion strains, named M1, M2C, M2T, V2, and V1, based on two major conformations of the pathological prion protein (PrPSc, type 1 and type 2), and the codon 129 genotype determining susceptibility and propagation efficiency. While the most frequent sCJD strains have been described in codon 129 homozygosis (MM1, MM2C, VV2) and heterozygosis (MV1, MV2K, and MV2C), the V1 strain has only been found in patients carrying VV. We identified six sCJD cases, 4 in Catalonia and 2 in Italy, carrying MV at PRNP codon 129 in combination with PrPSc type 1 and a new clinical and neuropathological profile reminiscent of the VV1 sCJD subtype rather than typical MM1/MV1. All patients had a relatively long duration (mean of 20.5 vs. 3.5 months of MM1/MV1 patients) and lacked electroencephalographic periodic sharp-wave complexes at diagnosis. Distinctive histopathological features included the spongiform change with vacuoles of larger size than those seen in sCJD MM1/MV1, the lesion profile with prominent cortical and striatal involvement, and the pattern of PrPSc deposition characterized by a dissociation between florid spongiform change and mild synaptic deposits associated with coarse, patch-like deposits in the cerebellar molecular layer. Western blot analysis of brain homogenates revealed a PrPSc type 1 profile with physicochemical properties reminiscent of the type 1 protein linked to the VV1 sCJD subtype. In summary, we have identified a new subtype of sCJD with distinctive clinicopathological features significantly overlapping with those of the VV1 subtype, possibly representing the missing evidence of V1 sCJD strain propagation in the 129MV host genotype.

074 ALK-positive desmoplastic Spitz naevus in a patient with corresponding ALK-positive anaplastic large cell lymphoma

Aim:Spitz naevus is a benign melanocytic tumour with distinct histopathological features of spindle-shaped melanocytes. An understanding of genetic aberrations can help to characterise the different subsets of Spitzoid neoplasms. Anaplastic lymphoma kinase (ALK) is a tyrosine kinase receptor that was first described in the pathogenesis of anaplastic large cell lymphoma (ALCL). ALK mutations have been reported in up to 10% of Spitz tumours.This study describes the rare occurrence of an ALK mutation in two different diseases in the same patient – ALCL and Spitz naevus. Method:Presentation, management, and clinical outcomes were retrospectively reviewed for a patient with ALK-positive ALCL and ALK-positive Spitz naevus at a tertiary paediatric hospital. Result:The patient was a 14-year-old female with a 12-month history of a red-brown plaque on the right shoulder.This was on a background stage III ALCL treated with chemotherapy and stem cell transplantation. She underwent surgical excision of the skin lesion. Histopathological examination showed an ALK-positive desmoplastic Spitz naevus. A bone marrow aspirate and trephine (BMAT) of the right axillary lymph node at the time of ALCL diagnosis also revealed an ALK mutation. She is currently in remission 2 years post stem cell transplantation. Conclusion:Our case reports on a rare coincidence of a patient having the same mutation for two distinct disease processes. There has been one similarly reported case in the literature in a patient with ALK-positive cutaneous ALCL and Spitz naevi with the same fusion partner gene (TPM3). Whilst this occurrence is not fully understood, further studies may identify whether this is an independent coincidence in two different cell lineages, or a fragile site similarity which may predispose to the same translocation event.

Modeling prostate cancer: What does it take to build an ideal tumor model?

Prostate cancer is frequently characterized as a multifocal disease with great intratumoral heterogeneity as well as a high propensity to metastasize to bone. Consequently, modeling prostate tumor has remained a challenging task for researchers in this field. In the past decades, genomic advances have led to the identification of key molecular alterations in prostate cancer. Moreover, resistance towards second-generation androgen-deprivation therapy, namely abiraterone and enzalutamide has unveiled androgen receptor-independent diseases with distinctive histopathological and clinical features. In this review, we have critically evaluated the commonly used preclinical models of prostate cancer with respect to their capability of recapitulating the key genomic alterations, histopathological features and bone metastatic potential of human prostate tumors. In addition, we have also discussed the potential use of the emerging organoid models in prostate cancer research, which possess clear advantages over the commonly used preclinical tumor models. We anticipate that no single model can faithfully recapitulate the complexity of prostate cancer, and thus, propose the use of a cost- and time-efficient integrated tumor modeling approach for future prostate cancer investigations.

BCOR-CCNB3 sarcoma with concurrent RNF213-SLC26A11 gene fusion: a rare sarcoma with altered histopathological features after chemotherapy

BackgroundChemotherapy is a common approach for cancer treatment, but intrinsic genetic mutations in different individuals may cause different responses to chemotherapy, resulting in unique histopathological changes. The genetic mutation along with the distinct histopathological features may indicate new tumor entities. BCOR-CCNB3 sarcomas is a kind of Ewing-like sarcomas (ELS) occurring mostly in bone and soft tissues. No gene fusion other than BCOR-CCNB3 has been found in this type of tumor.Case presentationWe herein report a case of 17-year-old male patient, presented with a mass on his left shoulder that was diagnosed as undifferentiated small round cell sarcoma according to core biopsy. The patient received 5 courses of preoperational chemotherapy, and the tumor was resected and analyzed. Primitive small round cells and larger myoid cells in the resected tumor tissue but not in biopsy were observed, and arterioles stenosis and occlusion were also detected, indicating a dramatic change of histopathological features of this tumor. In addition, the immunohistochemical results showed the altered staining patterns of BCOR, bcl2, CyclinD1, TLE1, AR, SMA, CD117, STAB2, CD56, and CD99 in tumor tissues after chemotherapy. Notably, RNA sequencing revealed a RNF213-SLC26A11 fusion in the tumor sample.ConclusionsThe BCOR-CCNB3 sarcoma with RNF213-SLC26A11 fusion may indicate a subset of tumors that undergo histopathological changes in response to chemotherapy. More similar cases in the future may help to clarify the clinical meanings of RNF213-SLC26A11 fusion in BCOR-CCNB3 sarcomas and the underlying mechanisms.

MO051: Single-Cell Transcriptomics of Lupus Nephritis with ANCA Positive

Abstract BACKGROUND AND AIMS Lupus nephritis (LN) is one of the most common complications of SLE that can lead to worsened kidney function or renal failure. Antineutrophil cytoplasmic antibodies (ANCA) are autoantibodies that are against antigens in the cytoplasm of neutrophils and monocytes and can lead to an autoimmune disease characterized by vascular necrotizing inflammation. The presence of ANCA in serum can also be found in SLE. Positive ANCA serology in patients with LN is associated with distinct histopathologic features on renal biopsy and seems to affect outcome of LN. Deeper understanding of the molecular pathogenesis in LN with ANCA positive is needed to identify novel targets improve the outcome of LN. METHOD Single-cell RNA sequencing (scRNA-seq) was applied to kidney biopsies from one LN patient with PR3-ANCA positive and a healthy adult kidney. We identified distinct cell clusters through unsupervised clustering analysis. Identification of the differentially expressed genes (DEGs) and enrichment analysis as well as the interaction between cells were also performed. RESULTS Unsupervised clustering analysis identified 15 distinct cell types including all of the renal intrinsic cells and major immune cells. The DEGs in kidney endothelial cells and intercalated cells were primarily enriched in genes involved in the regulation of inflammation and immune response including IL-17 signaling, TNF signaling, NOD-like receptor signaling and Th17 cell differentiation. Macrophages displayed increased expression of HLA-DRB5, which plays a central role in the immune system by presenting peptides derived from extracellular proteins. TYROBP, a gene plays a role in signal transduction and inflammation, was also high-expressed in macrophages from kidney of LN with PR3-ANCA positive. The receptor-ligand crosstalk analysis highlighted the interactions between endothelial cells and other cells in LN, which infers great importance in LN. CONCLUSION We provide a searchable resource of single-cell RNA sequencing to LN with PR3-ANCA positive to uncover intercellular interactions, elucidate key pathways underlying the pathogenesis and offer new insight into therapeutic targets of this unique type of LN.

Epidermotropism of inflammatory cells differentiates pyoderma gangrenosum from venous leg ulcers.

Pyoderma gangrenosum is an ulcerative autoinflammatory disease, lacking distinct histopathological characteristics to differentiate from other ulcerating conditions, like venous leg ulcers. The objective of this study was therefore to find histopathological characteristics of pyoderma gangrenosum in a head-to-head comparison to venous leg ulcers. Eight tissue samples of pyoderma gangrenosum, twelve samples of venous leg ulcers and six samples of healthy skin were stained using an immunohistological multi antigen staining technology. The immune infiltrate and its spatial distribution were analyzed with contextual tissue cytometry software using fluorescence images. The dense epidermal presence of CD45RO+ memory T cells and the rarefication of CD1a+ Langerhans cells in the epidermis were defining markers for pyoderma gangrenosum, implicating an epidermal immune reaction. In addition, high numbers of CD11c+ CD68+ pro-inflammatory M1 macrophages were detected in the dermis, significantly extending the numbers seen in venous leg ulcers. The histopathological differences found between pyoderma gangrenosum and venous leg ulcer can be used to distinguish between the two diseases and thus provide an important aid for the rapid initiation of adequate therapy. In addition, our data hint at an antigen-driven process in the epidermis, possibly involving CD1a+ Langerhans cells.

Cutaneous Myoepithelial Neoplasms on Acral Sites Show Distinctive and Reproducible Histopathologic and Immunohistochemical Features.

Cutaneous myoepithelial neoplasms are a heterogenous group of neoplasms with mixed tumors typically affecting the head and myoepitheliomas showing a predilection for the extremities. Their malignant counterparts, myoepithelial carcinoma, and malignant mixed tumor are exceptionally rare in the skin, and the morphologic criteria for malignancy are only poorly defined. The aim of the present study was to characterize the clinicopathologic features of myoepithelial neoplasms presenting on acral skin. The clinical and histopathologic features of 11 tumors were recorded, and follow-up was obtained. Immunohistochemistry was performed for S100, SOX10, glial fibrillary acidic protein, keratins, epithelial membrane antigen, p63, p40, smooth muscle actin, desmin, and PLAG1. The tumors mainly affected the feet of adults (range: 26 to 78 y; median: 47 y) with a predilection for the great toe and a male predominance of 1.8:1. Most tumors (91%) displayed a lobular architecture composed of solid and nested growth of epithelioid cells with plasmacytoid features in a myxoid or angiomatous stroma. Scattered cytologic atypia and rare duct differentiation were frequently noted. Three tumors with confluent cytologic atypia, infiltrative growth, and lymphovascular invasion were classified as malignant. By immunohistochemistry, the tumors were positive for S100, SOX10, keratins AE1/AE3, CK5/6 and CK7, and PLAG1. Local recurrence and bilateral pulmonary metastasis were observed in a patient presenting with a histopathologically benign-appearing tumor. Two patients with malignant tumors experienced local recurrences, and 1 developed metastasis to soft tissue, lung, and mediastinal lymph nodes. All patients are currently alive, all but 1 with no evidence of disease after a median follow-up interval of 96 months (range: 2 to 360 mo). In conclusion, acral myoepithelial neoplasms show distinctive and reproducible histopathologic and immunohistochemical features. They are best regarded as a distinctive subset of mixed tumors with features reminiscent of their salivary gland counterparts. While most tumors pursue a benign disease course, histopathologic features appear to be a poor indicator of prognosis.

HLA-DRB1∗16 and -DQB1∗05 alleles are strongly associated with autoimmune pancreatitis in a cohort of hundred patients

Background/objectivesAutoimmune diseases are often associated with human leukocyte antigen (HLA) haplotypes, indicating that changes in major histocompatibility complex (MHC)-dependent self-peptide or antigen presentation contribute to autoimmunity. In our study, we aimed to investigate HLA alleles in a large European cohort of autoimmune pancreatitis (AIP) patients. MethodsHundred patients with AIP, diagnosed and classified according to the International Consensus Diagnostic Criteria (ICDC), were prospectively enrolled in the study. Forty-four patients with chronic pancreatitis (CP) and 254 healthy subjects served as control groups. DNA was isolated from blood samples and two-digit HLA typing was performed with sequence-specific primer (SSP-) PCR. HLA allele association strength to AIP was calculated as odds ratio. ResultsWe uncovered a strong enrichment of HLA-DQB1 homozygosity in type 1 and type 2 AIP patients. Moreover, a significantly increased incidence of the HLA-DRB1∗16 and HLA-DQB1∗05 alleles and a concomitant lack of the HLA-DRB1∗13 allele was detected in AIP type 1 and type 2 patients. In contrast, the HLA-DQB1∗02 allele was underrepresented in the ‘not otherwise specified’ (NOS) AIP subtype. We detected no significant difference in the HLA-DRB3, HLA-DRB4 and HLA-DRB5 allele frequency in our cohort. ConclusionsAlthough AIP type 1 and type 2 are characterized by distinct histopathological characteristics, both subtypes are associated with the same HLA alleles, indicating that the disease might rely on similar immunogenic mechanisms. However, AIP NOS represented another subclass of AIP.

An odontogenic keratocyst: Correlating histopathological and clinicoradiographic features avoids a diagnostic dilemma

Odontogenic lesions are often seen as challenging diagnostic lesions. Odontogenic keratocyst (OKC) is a developmental odontogenic cyst, characterized by unique and distinct histopathologic characteristics and an aggressive biologic behavior. Inflammatory changes in the cystic lining epithelium may result in diagnostic dilemma histologically. In Such cases one should consider clinicoradiographic features for better diagnosis. As such lesions has high recurrence rate it is necessary to perform a periodic radiographic monitoring. This article integrate the necessary clinical and radiographic findings required to address the odontogenic keratocyst.

Tumor Immune Microenvironment in Lymphoma: Focus on Epigenetics.

Lymphoma is a neoplasm arising from B or T lymphocytes or natural killer cells characterized by clonal lymphoproliferation. This tumor comprises a diverse and heterogeneous group of malignancies with distinct clinical, histopathological, and molecular characteristics. Despite advances in lymphoma treatment, clinical outcomes of patients with relapsed or refractory disease remain poor. Thus, a deeper understanding of molecular pathogenesis and tumor progression of lymphoma is required. Epigenetic alterations contribute to cancer initiation, progression, and drug resistance. In fact, over the past decade, dysregulation of epigenetic mechanisms has been identified in lymphomas, and the knowledge of the epigenetic aberrations has led to the emergence of the promising epigenetic therapy field in lymphoma tumors. However, epigenetic aberrations in lymphoma not only have been found in tumor cells, but also in cells from the tumor microenvironment, such as immune cells. Whereas the epigenetic dysregulation in lymphoma cells is being intensively investigated, there are limited studies regarding the epigenetic mechanisms that affect the functions of immune cells from the tumor microenvironment in lymphoma. Therefore, this review tries to provide a general overview of epigenetic alterations that affect both lymphoma cells and infiltrating immune cells within the tumor, as well as the epigenetic cross-talk between them.

Association of recurrent APOBEC3B alterations with the prognosis of gastric-type cervical adenocarcinoma

ObjectiveGastric-type cervical adenocarcinoma (GCA) is a rare and aggressive type of endocervical adenocarcinoma (ECA) with distinct histopathologic features and unfavorable treatment outcomes, but no genomic prognostic factor has been revealed. We aimed to systematically investigate the somatic alterations of GCA at genome-wide level and evaluate their prognostic value. MethodsWe performed whole-exome sequencing (WES) on 25 pairs of tumor and matched normal samples to characterize the genomic features of Chinese patients with GCA and investigated their relations to histopathological characterizations and prognosis. The prognostic value of the genomic alterations was evaluated in a total of 58 GCA patients. ResultsMutations were commonly observed in reported GCA-related driver genes, including TP53 (32%), CDKN2A (20%), SKT11 (20%), BRCA2 (12%), SMAD4 (12%), and ERBB2 (12%). Recurrent novel trunk mutations were also observed in PBRM1 (12%), FRMPD4 (12%), and NOP2 (8%) with high variant allele frequency. Moreover, enrichment of the APOBEC signature was attributed to frequent gain of somatic copy number alteration (SCNA) of APOBEC3B (20%), which perfectly matched the nuclear-positive staining of APOBEC3B through immunohistochemistry. In contrast, APOBEC3B alteration was absent in patients with conventional type of ECA (N = 52). Notably, positive APOBEC3B was consistently enriched in patients with favorable prognosis in both the discovery cohort and an additional 33 GCA patients, thus indicating a significant association with lower relapse risk of GCA independent of cancer stage (P = 0.02). ConclusionOur results can aid understanding of the molecular basis of GCA in the Chinese population by providing genomic profiles and highlighting the potential prognostic value of APOBEC3B for GCA through routine clinical IHC.

Genomic analysis of focal nodular hyperplasia with associated hepatocellular carcinoma unveils its malignant potential: a case report

BackgroundFocal nodular hyperplasia (FNH) is typically considered a benign tumor of the liver without malignant potential. The co-occurrence of FNH and hepatocellular carcinoma (HCC) has been reported in rare cases. In this study we sought to investigate the clonal relationship between these lesions in a patient with FNH-HCC co-occurrence.MethodsA 74-year-old female patient underwent liver tumor resection. The resected nodule was subjected to histologic analyses using hematoxylin and eosin stain and immunohistochemistry. DNA extracted from microdissected FNH and HCC regions was subjected to whole exome sequencing. Clonality analysis were performed using PyClone.ResultsHistologic analysis reveals that the nodule consists of an FNH and two adjoining HCC components with distinct histopathological features. Immunophenotypic characterization and genomic analyses suggest that the FNH is clonally related to the HCC components, and is composed of multiple clones at diagnosis, that are likely to have progressed to HCC through clonal selection and/or the acquisition of additional genetic events.ConclusionTo the best of our knowledge, our work is the first study showing a clonal relationship between FNH and HCC. We show that FNH may possess the capability to undergo malignant transformation and to progress to HCC in very rare cases.