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Ectopic thymic carcinomas are rarely diagnosed in the thyroid gland, let alone in extrathyroid tissues. In the currently available literature, only five cases of extrathyroidal malignancies with thymic differentiation have been reported as arising in the major salivary glands. A 69-year-old female presented with a slow-growing palpable mass in the left parotid gland. Fine needle aspiration biopsy suggested metastatic cancer, whereas core needle biopsy revealed high-grade squamous cell carcinoma. The patient underwent left radical parotidectomy with selective ipsilateral lymph node dissection and subsequent radiation therapy. The surgical specimen was taken for histopathological examination. Microscopically, the tumor resembled thymic carcinoma. It was composed of large nests of squamoid cells with smooth contours, focally with a syncytial growth pattern, and accompanied by abundant lymphocytes with reactive lymphoid follicles. This appearance resembled a micronodular thymic carcinoma with lymphoid hyperplasia. Moreover, the tumor displayed expression of squamous markers (p40 and p63) and markers of thymic carcinoma (CD5 and CD117). Therefore, the final diagnosis of intrasalivary thymic carcinoma was rendered. The molecular analysis including next-generation sequencing demonstrated no variants of the strong, potential, or unknown clinical significance. The patient remains disease-free at 1-year follow-up. In the current case, we comprehensively present a clinical, microscopic, molecular, and radiological picture of CD5-positive squamous cell carcinoma of the parotid. We postulate that similar cases should be designated as intrasalivary thymic carcinoma analogically to similar thyroid tumors. Our case and the limited literature data indicate they should be distinguished from conventional squamous cell carcinoma of major salivary glands due to their rather favorable prognosis. [ABSTRACT FROM AUTHOR]

Simple Summary: The African dormice, also known as micro squirrels, are now becoming more and more popular as they present as laboratory animals, exhibited animals, or pets. However, we know very little about the diseases in these tiny rodents, such as tumors or infectious microorganisms. A 3-year-old, male African dormouse was taken to the veterinary clinic after showing vomiting and anorexia. A stomach lesion was noted through imaging examinations. The patient died after being treated for 2 months. The veterinary pathologist diagnosed the lesion as a gastric mast cell tumor, cancer occurs mostly in cats and rarely in other animals. This is the first time that a mast cell tumor is diagnosed in an African dormouse. We suggest that the mast cell tumor in digestive tracts should be listed in the differential diagnoses when an elder African dormouse or other small rodent shows chronic digestive signs. Mast cell tumors (MCTs) are well-known neoplasms derived from either mucosal or connective tissue mast cells. While well studied in several domestic species, MCTs are rarely documented in rodents. A three-year-old, male African dormouse (Graphiurus sp.) presented with a history of vomiting and anorexia for 3 months. Sonography revealed thickened gastric mucosa and hyperperistalsis. The patient died after receiving symptomatic treatment for 2 months. At necropsy, locally extensive, pale, thickened mucosal foci obscuring the first half of the stomach lumen was noted. Histological examination revealed moderately polymorphic, round, oval to spindle cells with amphophilic cytoplasmic granules infiltrating the mucosa to tunica muscularis, with moderate numbers of eosinophils. The mucosa was severely ulcerated with the proliferation of granulation tissue. The granules in most tumor cells exhibited metachromasia with the toluidine blue stain. Neoplastic cells revealed positive membranous immunoreactivity to KIT. Herein, we report the first case report of MCT in dormouse but also the first gastrointestinal MCT in a rodent species. [ABSTRACT FROM AUTHOR]

Simple Summary: Mast cell tumors (MCTs) are one of the most common skin tumors in dogs with variable clinical behavior ranging from benign lesions to those causing widespread metastasis. Prognostic factors have been intensively studied in cutaneous MCTs but are less commonly investigated in subcutaneous MCTs as the majority are benign. Activating mutations in exons 8 and 11 of c-kit, a gene that regulates proliferation and differentiation of mast cells, occur commonly in canine cutaneous MCTs and are strong predictors of prognosis. c-kit mutations have rarely been reported in subcutaneous MCTs. The goal of this study was to identify the prevalence of c-kit mutations in exons 8 and 11 in 216 canine subcutaneous MCTs and to investigate their association with other prognostic factors, including mitotic count, histologic grade, KIT pattern and proliferation markers. We detected c-kit mutations in exons 8 and 11 in 23 (10.6%) and 12 (5.56%) subcutaneous MCTs, respectively. c-kit mutations in exon 11 were associated with histologic high grade and a high mitotic count, suggesting that these parameters can predict the biological behavior of subcutaneous MCTs in a similar manner as in their cutaneous counterparts. The prognostic significance of internal tandem duplication (ITD) mutations in exons 8 and 11 of c-kit has been well-described for canine cutaneous mast cell tumors (MCTs), but c-kit mutations have rarely been reported in subcutaneous MCTs. The objective of this study was to identify the prevalence of ITD mutations in exons 8 and 11 of c-kit in canine subcutaneous MCTs and to investigate its association with histologic grade, KIT pattern, and proliferation markers. ITD mutations in exons 8 and 11 of c-kit, mitotic count, Ki67 index, AgNOR number, Ki67xAgNOR score, KIT pattern, and histologic grade (two-tier system) were retrospectively recorded for 216 dogs with subcutaneous MCTs. ITD mutations in exons 8 and 11 of c-kit were detected in 23 (10.6%) and 12 (5.56%) subcutaneous MCTs, respectively. Exon 11 mutations were significantly associated with Kiupel high grade (p < 0.001) and increased mitotic count (p < 0.001) compared to subcutaneous MCTs with no mutations in exons 8 or 11 (p = 0.002) or subcutaneous MCTs with a mutation in exon 8 (p = 0.001). There was no significant association of either c-kit mutation with KIT patterns or proliferation activity. This study identified a higher prevalence of ITD mutations in exons 8 and 11 of c-kit in subcutaneous MCTs than previously reported. Like their cutaneous counterpart, subcutaneous MCTs with exon 11 mutations were more likely to be histologically high grade and have a higher mitotic count, whereas such associations were not observed in subcutaneous MCTs with exon 8 mutations. [ABSTRACT FROM AUTHOR]

A 19-year-old woman presented with abdominal pain and a palpable mass, initially suspected to be a gastrointestinal stromal tumor (GIST) based on imaging. Surgical excision revealed a sclerotic spindle cell neoplasm with minimal cytological atypia, but immunohistochemistry (IHC) was negative for GIST-specific markers. The pan-negative IHC profile, along with calcification foci and low Ki67 index (<1%), led to a diagnosis of calcifying fibrous tumor (CFT). This case highlights the importance of precise diagnostic evaluation and consideration of rare entities like CFT. Comprehensive histopathological evaluation and IHC are essential diagnostic tools, as they can distinguish between GIST and CFT, leading to accurate treatment and patient management. This case underscores the value of thorough pathological assessment in resolving diagnostic challenges., Competing Interests: None declared., (Published by Oxford University Press and JSCR Publishing Ltd. © The Author(s) 2024.)

Objective: Despite advancements in treatment, multiple myeloma (MM) remains a challenging hematologic malignancy. It is crucial to stratify risk and perform prognostic assessment through various markers, including the cluster of differentiation 56 (CD56) and thecluster of differentiation 117 (CD117) expression. However, the relationship of these markers with MM-related survival remains unclear. In this context, the objective of this study isto investigate the prognostic implications of CD56 and CD117 expression and associated clinical features in MM patients., Materials and Methods: The population of this retrospective single-center study consisted of adult MM patients whose CD56 and CD117 expressionswere analyzed. Patients were divided into four groups according to their immunophenotypes: CD56+ CD117-, CD56-CD117+, CD56+CD117+, and CD56-CD117-.These groups were compared in terms of demographic and clinical characteristics, response to treatment, and survival outcomes., Results: Of the 168 MM patients included in the study, CD56 positive, CD117 positive,CD56, and CD117 double-positive and double negative were observed in 57.1%, 38.1%, 21.4%, and 26.2%, respectively. Patients with double positivehad significantly higher cytogenetic risk and significantly lower overall response rate (ORR) compared toother patients(p<0.001 for both cases). ORR and overall survival (OS) were significantly lower in CD56 positivepatients than those CD56 negative (p=0.017 and p=0.004, respectively). Mortality rates were significantly higher in CD56 positive patients and CD117 positive than in those with double negative(p<0.001 and p=0.002). Double negative patients had significantly lower ORR and OS and higher mortality than others (p=0.001, p=0.002, and p<0.001, respectively). The high cytogenetic risk was found to bean independent predictor of shorter OS (p>0.001)., Conclusion: The study's findings revealed that CD56 and CD117 double- positive MM patients had poorer prognosis, lower ORR, shorter OS, and higher mortality.

c-kit is a classical proto-oncogene that encodes a receptor tyrosine kinase (RTK) that responds to stem cell factor (SCF). C-KIT signaling is a critical regulator of cell proliferation, survival, and migration and is implicated in several physiological processes, including pigmentation, hematopoiesis and gut movement. Accumulating evidence suggests that dysregulated c-KIT function, caused by either overexpression or mutations in c-kit, promotes tumor development and progression in various human cancers. In this review, we discuss the most important structural and biological features of c-KIT, as well as insights into the activation of intracellular signaling pathways following SCF binding to this RTK. We then illustrate how different c-kit alterations are associated with specific human cancers and describe recent studies that highlight the contribution of c-KIT to cancer stemness, epithelial-mesenchymal transition and progression to metastatic disease in different experimental models. The impact of tyrosine kinase inhibitors in treating c-KIT-positive tumors and limitations due to their propensity to develop drug resistance are summarized. Finally, we appraise the potential of novel therapeutic approaches targeting c-KIT more selectively while minimizing toxicity to normal tissue.

Low-grade oncocytic tumor (LOT) of kidney is a newly emerging provisional renal tumor entity that carries good prognosis. Here we present a case of low grade oncocytic tumor of kidney in a 68-year-old male with detailed immunohistochemical and ultrastructural description, to add to the existing knowledge about this entity. The importance of documenting low-grade oncocytoma in the literature is its indolent clinical behavior, characteristics gross and microscopic, and immunohistochemical features. The diagnosis of low-grade oncocytoma can be suspected on morphological ground but should be confirmed by immunohistochemistry. [ABSTRACT FROM AUTHOR]

Gastrointestinal stromal tumors are the most common mesenchymal tumors of gastrointestinal tract which comprise <1% of all primary gastrointestinal malignancies. These tumors show mutations in the KIT gene or platelet-derived growth factor receptor-A gene and usually stains positively for CD117. Very few cases of extragastrointestinal GIST (EGIST) have been reported in literature which originate from omentum and mesentery as per our knowledge. Here, we report a case of EGIST arising from omentum with no connection to gastrointestinal tract organs in a 60-year-old woman who presented with abdominal pain for 2–3 months. Intraoperative findings showed the presence of multiple globular masses and nodules in the peritoneal cavity. Microscopically, the spindled tumor cells were arranged in interlacing fashion. Immunohistochemistry showed positivity for CD117 and negativity for smooth muscle actin (SMA). Thus, EGIST should always be considered as a differential diagnosis for nodular mesenteric masses. [ABSTRACT FROM AUTHOR]

Objective: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasias of the gastrointestinal system (GIS). The malignancy potential of GISTs may vary ranging from indolent tumors to progressive malignant tumors. This study aims to define clinicopathological and immunohistochemical features of GISTs diagnosed in our institute with a review of the literature. Methods: A total of 28 GIST cases were included in the study. The Hematoxylin&Eosin stained slides of surgical resection materials and cell blocks and immunohistochemistry performed slides were reviewed by a pathologist. The immunohistochemical expression with CD117, DOG-1, CD34, SMA, and S100 was scored between 0 and 3 points according to staining intensity. Descriptive statistics were used in the study. The demographic data, prognostic histopathological, and immunohistochemical findings are evaluated with the literature indications. Results: Eleven of the cases were male and seventeen were female. The age range was 18-88. The most common site of GISTs was the stomach, followed by the small intestine, colorectal region, and, esophagus. Twenty of the tumors were resected surgically, four were endoscopic biopsy material and four were fine-needle aspiration biopsies. The tumor size in measurable materials ranged from 0,2 to 22 cm. The mitotic count in 50 HPF ranges from 0 to 10. Seven of the GISTs were high grade and the remaining 21 were low grade. The majority of the cases were composed of spindle cells, 3 were epithelioid and 3 were the mixed type with spindle and epitheloid cells. Conclusions: A variety of criteria has been proposed to estimate the malignancy potential of GISTs and predict prognosis but definite prognostic criteria remain uncertain. Further studies with larger series of GISTs consisting of different types of biopsy materials may help define criteria to predict prognosis precisely. [ABSTRACT FROM AUTHOR]

Simple Summary: Galectins are a family of β-galactoside binding proteins whose levels are altered in various stages of different types of cancer. This study provides an analytical comparison of 50 frequently mutated genes in two common cancers and the serum levels of the galectin proteins. The goal is the revelation of potential relationships between the mutation status of these genes and serum levels of galectins. We found that mutations in the KIT gene (which codes for the proto-oncogene c-KIT protein) are associated with increased circulating levels of certain galectins. We also found that patient samples originating from brain tissue have a higher likelihood of having a mutation in the KIT gene. Understanding the relationship between cancer-critical gene mutations and serum galectin levels could provide a feasible and non-invasive avenue to better understand the tumor's unique genetic profile. To investigate a potential role for galectins as biomarkers that enable diagnosis or prognostication of breast or non-small cell lung cancer, the serum levels of galectins -1, -3, -7, -8, and -9 of cancer patients determined by ELISA assays were compared to the mutation status of 50 known cancer-critical genes, which were determined using multiplex PCR in tumors of the same patients. Mutations in the KIT proto-oncogene, which codes for the c-Kit protein, a receptor tyrosine kinase, correlated with higher levels of galectins -1, -3, -8, and -9 in breast cancer patients and galectin-1 in non-small cell lung cancer patients. Mutations in the KIT gene were more likely found in brain metastases from both of these primary cancers. The most common KIT mutation in our panel was p.M541L, a missense mutation in the transmembrane domain of the c-Kit protein. These results demonstrate an association between KIT oncogenic signaling and elevated serum galectins in patients with metastatic disease. Changes in protein trafficking and the glycocalyx composition of cancer cells may explain the observed alterations in galectin expression. This study can be useful for the targeted selection of receptor tyrosine kinase and galectin inhibitor anti-cancer treatments. [ABSTRACT FROM AUTHOR]

Abstract Background Advanced breast cancer (BC) impact immune cells in the blood but whether such effects may reflect the presence of early BC and its therapeutic management remains elusive. Methods To address this question, we used multiparametric flow cytometry to analyze circulating leukocytes in patients with early BC (n = 13) at the time of diagnosis, after surgery, and after adjuvant radiotherapy, compared to healthy individuals. Data were analyzed using a minimally supervised approach based on FlowSOM algorithm and validated manually. Results At the time of diagnosis, BC patients have an increased frequency of CD117+CD11b+ granulocytes, which was significantly reduced after tumor removal. Adjuvant radiotherapy increased the frequency of CD45RO+ memory CD4+ T cells and CD4+ regulatory T cells. FlowSOM algorithm analysis revealed several unanticipated populations, including cells negative for all markers tested, CD11b+CD15low, CD3+CD4−CD8−, CD3+CD4+CD8+, and CD3+CD8+CD127+CD45RO+ cells, associated with BC or radiotherapy. Conclusions This study revealed changes in blood leukocytes associated with primary BC, surgical removal, and adjuvant radiotherapy. Specifically, it identified increased levels of CD117+ granulocytes, memory, and regulatory CD4+ T cells as potential biomarkers of BC and radiotherapy, respectively. Importantly, the study demonstrates the value of unsupervised analysis of complex flow cytometry data to unravel new cell populations of potential clinical relevance.

Plasma cell leukemia (PCL) is a rare (1-2 %) aggressive plasma cell dyscrasia (PCD) with a poor prognosis and characterized by the presence of more than 20% circulating plasma cells (PCs). Multicolor Flowcytometry is used for differentiating PCs in PCL. In this study, we aimed to compare the clinical, laboratory findings and immunophenotypic profiles of patients with PCL. A total of 512 patients were investigated for PCD in our hospital between 2011-2019. The immunophenotypic profile (including, CD27, CD28, CD38, CD138, CD45, CD117, CD19, CD20, CD56, CD33, CD81, and ckappa /clambda,) were evaluated retrospectively. The clinical findings, pathology reports, immunofixation electrophoresis and MFC results of three patients with PCL were reevaluated using 6 color multiparametric flow cytometry (MFC). Only three patients were diagnosed as PCL. PCs population defined by the co-expression of CD38 and CD138 was observed as 50%, 53%, 60%, respectively. Expression of each CD56, CD117, CD20, CD45 was seen in individual cases. CD19 was negative in all cases. Cytoplasmic kappa light chain expression was detected only in one case. Two of the cases were primary and the other was secondary PCL. Bortezomib-based treatment was initiated. Overall survival of primary PCL cases were 24 months and 6 months, whereas secondary PCL was four months. Co-expression of CD38 and CD138 in identifying PCs with MFC may be considered the best combination and leads to early diagnosis within hours and appropriate treatment in patients with PCL. [Med-Science 2021; 10(2.000): 455-61]

Yomna M El-Meligui,1 Heba E Abd Elrhman,2 Ahmad Salahuddin,3 Manal Ali Hamouda,4 Amira B Kassem5 1Department of Clinical Pathology, National Cancer Institute, Cairo University, Cairo, Egypt; 2Department of Clinical Pathology, Faculty of Medicine, Zagazig University, Zagazig, Egypt; 3Biochemistry Department, Faculty of Pharmacy, Damanhour University, Damanhour, Egypt; 4Clinical Pharmacy Department, Faculty of Pharmacy, Ahram Canadian University, Giza, Egypt; 5Clinical Pharmacy and Pharmacy Practice Department, Faculty of Pharmacy, Damanhour University, Damanhour, EgyptCorrespondence: Amira B Kassem Email amira.kassem@pharm.dmu.edu.egIntroduction: Acute myeloid leukemia (AML) is the most common type of acute leukemia in adults. HLA-DR and CD117 (c-Kit) are important diagnostic markers of AML. Our objective is to determine the prognostic significance of HLA-DR and CD117 expressions in newly diagnosed AML patients and determine the correlation between HLA-DR and CD117 expressions and other prognostic markers such as cytogenetic abnormalities, FLT3-ITD, response to treatment, and patient’s survival.Methods: This study included 100 newly diagnosed AML patients. All patients were subjected to clinical, morphological, cytochemical, cytogenetic analysis, molecular genetic analysis to detect FLT3-ITD, and Flowcytometric detection of HLA-DR, CD117, and CD 34.Results: The results showed that HLA-DR expression was found in 75 patients (77.3%), while CD117 expression was found in 63 patients (64.9%). Patients with HLA-DR expression showed significantly higher mean Hb concentration, significantly higher platelet count, associated with AML-FAB subtypes (M0, M1, and M2), CD34 expression, and favorable cytogenetic group. M3 subtype was significantly associated with HLA-DR-ve. While patients with CD117 expression showed significantly lower platelets count. Double positive patients (HLA-DR+ve/CD117+ve) showed significant association with the intermediate cytogenetic group, while double-negative patients (HLA-DR-ve/CD117-ve) were associated with the favorable and intermediate cytogenetic group and either positive (HLA-DR+ve /CD117-ve or HLA-DR-ve/CD117+ve) associated with poor cytogenetic groups. FLT3-ITD expression had significantly worse overall survival.Conclusion: The current study suggested that the expression of CD117 and HLA-DR may be a prognostic marker in AML, as they are associated with M0, M1, and M2 FAB subtypes; moreover, patients with combined HLA-DR and CD117 positive expression are associated with CD34 expression and intermediate cytogenetic group.Keywords: acute myeloid leukemia, HLA-DR, CD117, CD34, FLT3-ITD, response, cytogenetic

Grading, immunohistochemistry and c-kit mutation status are criteria for assessing the prognosis and therapeutic options of canine cutaneous mast cell tumours (MCTs). As a subset, canine digital MCTs have rarely been explored in this context. Therefore, in this retrospective study, 68 paraffin-embedded canine digital MCTs were analysed, and histological grading was assessed according to Patnaik and Kiupel. The immunohistochemical markers KIT and Ki67 were used, as well as polymerase chain reaction (PCR) for mutational screening in c-kit exons 8, 9, 11 and 14. Patnaik grading resulted in 22.1% grade I, 67.6% grade II and 10.3% grade III tumours. Some 86.8% of the digital MCTs were Kiupel low-grade. Aberrant KIT staining patterns II and III were found in 58.8%, and a count of more than 23 Ki67-positive cells in 52.3% of the cases. Both parameters were significantly associated with an internal tandem duplication (ITD) in c-kit exon 11 (12.7%). French Bulldogs, which tend to form well-differentiated cutaneous MCTs, had a higher proportion of digital high-grade MCTs and ITD in c-kit exon 11 compared with mongrels. Due to its retrospective nature, this study did not allow for an analysis of survival data. Nevertheless, it may contribute to the targeted characterisation of digital MCTs.

Right up to now, there has not been an effective or safe therapy for trichinellosis. Thus, this study aimed to determine the efficacy of prophylactic and therapeutic regimens of progesterone and mifepristone on the intestinal and muscular phases of experimental Trichinella spiralis infection compared to albendazole. Seven distinct groups of mice were divided as follows: negative, positive, and drug control groups, as well as prophylactic and treatment groups using mifepristone and progesterone. Mice were sacrificed on the 7th and 37th days after infection. Treatment efficacy was evaluated using parasitological techniques, histopathological examination, immunohistochemical staining, and ultrastructural morphological analysis of adult worms by scanning electron microscopy. The mice groups received progesterone (300 ng/ml) and mifepristone (100 ng/ml). They demonstrated a significant improvement in intestinal and muscular inflammation and a statistically significant decline in the adult worm burden and encysted larvae (P < 0.001). Moreover, immunohistochemical staining of vascular endothelial growth factor and mucosal mast cell analyses were coincided with the obtained parasitological results. There was notable destruction and degeneration of the adult worm tegument by using both drugs. The current study pointed out that progesterone and mifepristone may provide new insights regarding the development of vaccines and drug protocols to treat trichinellosis through their combined action in reducing the inflammation, affecting the intestinal immune cell, and decreasing the adult worm burden, and larval capsule development. [Display omitted] • Treatment of trichinellosis by progesterone and mifepristone was assessed. • They succeeded in reducing adults and larvae counts and improved IHC scoring. • Their efficacy was indicated by degeneration of the adult worm tegument. [ABSTRACT FROM AUTHOR]

While eosinophilic esophagitis (EOE) is defined by histologic presence of eosinophils, a few studies have established the presence of mast cells in EOE and even shown their correlation with symptom persistence despite resolution of eosinophils. Expression of aberrant mast cell markers CD25 and CD2 have not been studied in EOE. This study quantifies the number of hotspot cells per high power field expressing CKIT/CD117, tryptase, CD25, CD2 and CD3 by immunohistochemical stains in endoscopic esophageal biopsies of the following three cohorts: (1) established and histologically confirmed EOE, (2) suspected EOE with biopsies negative for eosinophils, and (3) no history of or suspicion for EOE with histologically unremarkable biopsies. In this study, mast cells were highlighted by CKIT and tryptase in EOE, and not seen in other clinically mimicking cases. There were also significantly higher densities of CD25 and pan-T-cell marker staining in EOE cases. These findings suggest an inflammatory cellular milieu in EOE, beyond just eosinophils, that can be demonstrated by immunohistochemistry, and that invite further study into the role that these cells may play in EOE. • Mast cells by CKIT and tryptase found in eosinophilic esophagitis • Significant CD25 expression found in eosinophilic esophagitis • Significant T-cells by CD2 and CD3 found in eosinophilic esophagitis [ABSTRACT FROM AUTHOR]

Objectives Hypocellular bone marrow (BM) disorders comprise heterogeneous entities associated with peripheral cytopenias and decreased production of hematopoietic cells in BM. This study was undertaken to analyze immunohistochemical expression of CD34, CD117, and p53 in morphologically diagnosed patients of hypocellular BM (aplastic anemia [AA], hypocellular myelodysplastic syndrome [h-MDS], and hypocellular acute myeloid leukemia [h-AML]). Materials and Methods BM specimens were obtained from patients presenting with pancytopenia/bicytopenia. On 30 patients diagnosed as hypocellular BM, immunohistochemistry (IHC) for CD34, CD117, and p53 was performed. Results BM cellularity was < 30% in all (100%) patients. Blast count was increased in h-MDS and h-AML. Features of dysplasia were noted in six (20%) patients. Out of these, three patients were diagnosed as h-MDS having bilineage/trilineage dysplasia, and the other three patients were of AA (11.5% patients) displaying only dyserythropoiesis. On IHC, percentage of BM CD34+ cells was increased in h-MDS+ h-AML (3.87 ± 0.86) as compared with AA (0.19 ± 0.15) and controls (0.81 ± 0.21), p = 0.01. Percentage of BM p53+ cells was also increased in h-MDS+ h-AML (2.9 ± 2.07) as compared with AA and controls, which did not show any p53+ cells, p = 0.0. No statistically significant difference was observed in the expression of CD117 in h-MDS+ h-AML (4.95 ± 3.40) compared with AA (4.49 ± 1.07), p = 0.99. Conclusion The study demonstrates the usefulness of CD34 and p53 immunoexpression as an important ancillary method in distinguishing various hypocellular BM disorders, especially h-MDS and AA. However, the role of CD117 remains unclear and needs to be evaluated further by larger studies. [ABSTRACT FROM AUTHOR]

Background: Gastrointestinal stromal tumour (GIST) is a soft? tissue sarcoma of the gastrointestinal (GI) tract. These are known to arise from the interstitial cells of Cajal. The aim of this study was to understand the clinical, histopathological, immunohistochemical characteristics of GISTs in a tertiary care centre. Material Methods: This study comprises of 45 patients who were diagnosed as GIST and were registered in the department of Pathology from 1st May 2018 to 31st August 2021. The demographic and clinicopathological data was collected and analysed carefully. Results: Most of the patients presenting with GIST were in the 6th decade (23 cases, 51.1%) with females (35 cases, 77.8%) being more commonly affected than males. Stomach was the most common site of origin (30 cases, 66.7%) in our study, with abdominal pain (18 cases, 40%) being the most common presenting symptom. Spindle cell type was the most commonly reported histological type in 35 cases (77.8%). 80% of GISTs showed low mitotic counts. Majority of cases (35 cases, 77.8%) belonged to intermediate risk category. Conclusion:With the availability of various risk categorization systems, GISTs can be treated on the basis of assessment of array of prognostic factors, risk of metastasis and recurrence which will further aid in lowering the morbidity and mortality associated with GISTs. [ABSTRACT FROM AUTHOR]

Squamous cell carcinoma (SCC) and Basal cell carcinoma (BCC) of the skin are the most common malignant tumors in humans. The c-Kit (CD117) is a tyrosine kinase receptor protein that affects the behavior of some tumors and can be a target for new treatments. This study was designed to determine the expression of CD117 in patients with SCC and BCC. In this retrospective study, 69 paraffin blocks of specimens with a diagnosis of SCC and BCC from limbs, head/neck, trunk, and unknown sites were selected. Tumor tissue samples of 40 SCC and 29 BCC cases were then analyzed by immunohistochemistry. The monoclonal CD117 antibody was used. The severity and extent of tumor staining were grouped as follows: negative; weakly positive; moderately positive; and strongly positive. The CD117 was detected positive in 26 (89.7%) BCCs and only in 5 (12.5%) of SCCs. We detected a significant difference between the expression of CD117 in patients with SCC and BCC (P < 0.05). No significant relationship was shown between the marker expression and the lesion site in patients with SCC or BCC (P > 0.05). On the contrary, a significant relationship between CD117 expression and histopathologic grading was identified in patients with SCC (P < 0.05). According to our results, the expression of CD117 is significantly increased in BCCs than SCCs and this may be of benefit for diagnostic purposes in challenging cases and also for therapeutic purposes including targeted therapy if indicated.

Background and purpose: Multinodular goiter is a benign enlargement of thyroid gland and papillary thyroid carcinoma is the most common type of thyroid cancer. Today, immunohistochemical markers can be used in diagnosis and prognosis of tumors. The aim of this study was to compare the expression of CD117 in multinodular goiter and papillary thyroid carcinoma and its association with prognostic factors. Materials and methods: In this cross-sectional study, samples of thyroid tissue from 60 multinodular goiter and 60 papillary thyroid carcinoma cases who underwent thyroidectomy in Tehran Mostafa Khomeini Hospital during 2011-18, were evaluated for CD117 expression via immunohistochemistry. The expression intensity was scored 0-3. Results: CD117 was expressed in all samples with generally lower expression scores in malignant samples: 95% and 5% of malignant cases showed scores 1 and 2, respectively. Almost 52% and 48% of benign cases showed score 1 and scores 2 and 3, respectively (P

Background: Gastrointestinal stromal tumour (GIST) is a soft tissue sarcoma of the gastrointestinal (GI) tract. These are known to arise from the interstitial cells of Cajal. Aim: The aim of this study was to understand the clinical, histopathological, immunohistochemical characteristics of GISTs in a tertiary care centre. Material & Methods: This study comprises of 45 patients who were diagnosed as GIST and were registered in the department of Pathology from 1st May 2018 to 31st August 2021. The demographic and clinicopathological data were collected and analysed carefully. Results: Most of the patients presenting with GIST were in the 6th decade (23 cases, 51.1%) with females (35 cases, 77.8%) being more commonly affected than males. Stomach was the most common site of origin (30 cases, 66.7%) in our study, with abdominal pain (18 cases, 40%) being the most common presenting symptom. Spindle cell type was the most commonly reported histological type in 35 cases (77.8%). 80% of GISTs showed low mitotic counts. Majority of cases (35 cases, 77.8%) belonged to intermediate risk category. Conclusion: With the availability of various risk categorization systems, GISTs can be treated on the basis of assessment of array of prognostic factors, risk of metastasis and recurrence which will further aid in lowering the morbidity and mortality associated with GISTs.

The receptor tyrosine kinase c-KIT (CD117) has a key role in hematopoiesis and is a marker for endothelial and cardiac progenitor cells. In vivo, deficiency of c-KIT is lethal and therefore using CRISPR/Cas9 editing we generated heterozygous and homozygous c-KIT knockout human embryonic stem cell (ES cell) lines. The c-KIT knockout left ES cell pluripotency unaffected as shown by immunofluorescence and trilineage differentiation potential. Heterozygous and homozygous c-KIT knockouts showed complete loss of exon 17, resulting in ablation of c-KIT protein from the cell surface. c-KIT knockout ES cells provide a valuable tool for further investigating c-KIT biology.

Aims: The diagnosis of mastocytosis in skin biopsies can be challenging ‐ particularly in cases with very few mast cells. More diagnostic criteria are needed. Methods and results: We analyzed 103 skin biopsies from patients with mastocytosis and compared them with biopsies from inflammatory skin lesions and normal skin. Using CD117 immunostaining, we determined the mast cell distribution pattern, the percentage of mast cells in the inflammatory infiltrate, and the mast cell count per mm². We found that a sheet‐like or subepidermal distribution of mast cells was specific for mastocytosis. The most significant feature was the percentage of mast cells and not the mast cell count. We found that a mast cell percentage above 40% was fully specific in both adults and children but lacked sensitivity, especially in adults. In children, all cases with a percentage below 40% harbored a number of mast cells above 90 per mm², allowing a straightforward diagnosis. In adults, the diagnosis was more challenging and cases with less than 40% of mast cells could be diagnosed on account of a number of mast cells above 40 per mm², with 88.5% sensitivity and 95.2% specificity. Additional signs might be useful in difficult cases. However, CD25 immunostaining was not useful. Conclusions: We confirmed that the criteria currently applied in the bone marrow were not appropriate for the skin. Accordingly, we developed an algorithm for the diagnosis of mastocytosis in skin biopsies with a high level of interrater reproducibility (mean kappa 0.8). [ABSTRACT FROM AUTHOR]

A 6‐year‐old castrated male American Pit Bull Terrier dog was presented for evaluation of acute onset of tonic‐clonic seizures, anorexia, and vomiting. On physical examination, neurologic signs, such as generalized proprioceptive ataxia, salivation, circling to the right, and absent patellar reflexes bilaterally, were noted. A complete blood cell count revealed mild hemoconcentration and an inflammatory leukogram, while a chemistry panel showed severe azotemia, marked hypochloremia, and a severe titrational metabolic acidosis, suggesting possible ethylene glycol intoxication. However, an irregularly round, small mass was identified in the large intestine on abdominal ultrasound. Additionally, bilateral hyperechoic renal cortices with medullary rim sign were suggestive of acute nephritis or tubular necrosis. The cytologic evaluation of a fine‐needle aspiration biopsy of the abdominal mass revealed a large population of mesenchymal cells, suggesting the presence of neoplasia. Due to the worsening of symptoms, the dog was humanely euthanized. Necropsy confirmed ethylene glycol intoxication, and the incidental finding of a neoplastic intestinal mass was diagnosed as spindle cell sarcoma. Immunohistochemical staining showed strong, diffuse positivity for CD117, smooth muscle actin, and S‐100, indicating the final diagnosis of a spindle cell type gastrointestinal stromal tumor (GIST). This report briefly discusses the classifications of nonlymphoid, nonangiogenic intestinal mesenchymal tumors, characteristics of GISTs, and the importance of the immunohistochemical classification of mesenchymal tumors of the gastrointestinal tract. [ABSTRACT FROM AUTHOR]

BACKGROUND: Gastrointestinal stromal tumors arise from the interstitial cells of Cajal, or their precursors, located in the wall of the digestive tract. It affects groups of patients of different ages, from children to the elderly, with a median age at diagnosis of 64 years. CLINICAL CASE: A 15-year-old pediatric patient who started with bleeding from the upper digestive tract, associated with melenic feces. One year later, he was readmitted to the medical service due to asthenia, weakness, nausea, dizziness, and holocranial headache. Endoscopy and ultrasound revealed a multilobulated, ulcerated submucosal tumor with transmural invasion; Abdominal tomography reported thickening of the mucosa of the lesser curvature of the stomach, in the antrum, and polypoid multinodular lesions measuring 24 x 22 mm in the axial axis. She underwent surgery and found a tumor in the gastric antrum, 6 cm in diameter, without infiltration into the pylorus or duodenum; Antrectomy was performed with a Billroth 3 gastro-jejunal anastomosis. The histological study reported a neoplasm that extended from the submucosa to the internal muscular layer, with infiltration of neoplastic cells. Immunohistochemistry resolved: focal positive smooth muscle actin, and positive CD34 and CD117 on the neoplastic cell membrane. The diagnosis of gastrointestinal stromal tumor is established. CONCLUSIONS: The case presented here is of important importance, since it is an adolescent patient, with clinical and radiological manifestations, histological and immunohistochemical findings, treatment, and evolution different from gastrointestinal stromal tumors enlarged in adults. [ABSTRACT FROM AUTHOR]

The aim: to find the optimal combination of immunohistochemical markers for differential diagnosis and prognosis of small cell lung cancer in small biopsy samples. Materials and methods. The tumor specimens were divided into 3 groups: 1) 25 biopsy samples of small cell lung cancer before treatment; 2) 25 samples of small cell lung cancer procured from autopsies of patients, who underwent chemotherapy; 3) 15 biopsy samples of other lung tumors histologically similar to SCLC. All tumor samples were formalin fixed and paraffin embedded (FFPE). Immunohistochemical study performed with 5 primary antibodies: CD56, p16ink4A, TTF-1, CD117, Ki-67. Results. TTF-1 was positive in all small cell lung cancer, lung adenocarcinomas and atypical carcinoids. Expression of CD56 was positive in 100 % of tumors from 1st group and 92 % of these tumors had more than 25 % of positive tumor cells. Expression of p16ink4A was significantly higher in 1st group than in the 3rd one (p<0,001). The stepwise logistic regression was used for finding the best markers for differential diagnosis of small cell lung cancer in small biopsy samples. The next combination of markers was chosen: TTF-1/CD56 (score 2-4)/p16 ink4A/CD117 (sensitivity - 80 %; specificity - 86.67 %; p<0,001) where "score 2-4" means expression of CD56 more than in 25 % tumor cells. Expression of Ki-67 was higher in the 2nd group compared with the 1st one (p<0,001). Conclusion. Evaluation of p16 expression can be used as additional marker for differential diagnosis of small cell lung cancer. The following combination of markers: TTF-1/CD56 (score2-4)/p16 ink4A/CD117 could be useful in diagnosis of small cell lung cancer in small biopsy samples and in the choice of targeted chemotherapy. The further study in paired tumor samples of small cell lung cancer before and after chemotherapy is required to prove the significance of changes in expression of Ki-67, CD56, CD117 and p16ink4A. [ABSTRACT FROM AUTHOR]

The aging of the immune system is not only an inevitable result but also an important cause of physical aging. The aging of the immune system is rooted in the aging of hematopoietic cells (HSCs), which manifests as decreasing functionality of the adaptive immune system and the innate immune system. C57BL/6 mice of different ages were collected in this study to better understand the changes in the structures of the innate and adaptive immune systems in individuals of different ages and the distribution and changes in immune cells with stem cell properties. The immune cells of the innate and adaptive immune systems, including DCs, monocytes, macrophages, CD4+ T lymphocytes, CD8+ T lymphocytes, and B lymphocytes, were assessed, and the proportions of cells with stem cell properties among these immune cell populations were also tested. Overall, immune cells in the peripheral blood, spleen, and bone marrow of mice exhibit certain regular properties with increasing age. The trend of changes in immune cells in different immune organs differs with age. The changes in lymphocytes in the peripheral blood are more sensitive. Their proportions increase slowly with age and then decrease rapidly to a very low level (less than 5%) after a certain point (9 or 13 months old). Nine to 13 months of age is the most critical time point for assessing changes in the immune system of mice and the most critical time point for detecting changes in the proportion of stem cells. After 13 months of age, the balance and stability of stem cells in mice are disrupted, and animals begin to age rapidly. The ratio of Ly6A to E+CD117+ cells in the peripheral blood, particularly lymphocytes involved in adaptive immunity, represents a specific marker for predicting immune senescence and body senescence. [ABSTRACT FROM AUTHOR]

Abstract Objective The same immuno-phenotype between HLA-DR-negative acute myeloid leukemia (AML) and acute promyelocytic leukemia (APL) causes APL rapid screening to become difficult. This study aimed to identify the associated antigens for APL and the best model in clinical uses. Results A total of 36 APL (PML–RARA+) and 29 HLA-DR-negative non-APL patients enrolled in this study. When a cut-off point of 20% events was applied to define positive or negative status, APL and non-APL patients share a similar immuno-phenotype of CD117, CD34, CD11b, CD13, CD33, and MPO (P > 0.05). However, expression intensity of CD117 (P = 0.002), CD13 (P

Conditioning chemotherapy is used to deplete hematopoietic stem cells in the recipient’s marrow, facilitating donor cell engraftment. Although effective, a major issue with chemotherapy is the systemic genotoxicity that increases the risk for secondary malignancies. Antibody conjugates targeting hematopoietic cells are an emerging non-genotoxic method of opening the marrow niche and promoting engraftment of transplanted cells while maintaining intact marrow cellularity. Specifically, this platform would be useful in diseases associated with DNA damage or cancer predisposition, such as dyskeratosis congenita, Schwachman-Diamond syndrome, and Fanconi anemia (FA). Our approach utilizes antibody-drug conjugates (ADC) as an alternative conditioning regimen in an FA mouse model of autologous transplantation. Antibodies targeting either CD45 or CD117 were conjugated to saporin (SAP), a ribosomal toxin. FANCA knockout mice were conditioned with either CD45-SAP or CD117-SAP prior to receiving whole marrow from a heterozygous healthy donor. Bone marrow and peripheral blood analysis revealed equivalent levels of donor engraftment, with minimal toxicity in ADC-treated groups as compared with cyclophosphamide-treated controls. Our findings suggest ADCs may be an effective conditioning strategy in stem cell transplantation not only for diseases where traditional chemotherapy is not tolerated, but also more broadly for the field of blood and marrow transplantation.

Background: The etiopathogenesis of congenital ureteropelvic junction obstruction (UPJO) has been inconclusive in spite of the numerous studies carried out to find the possible causative factor. The results of different studies have been conflicting and contradictory. It has been postulated that the interstitial cells of Cajal (ICC) are the pacemaker cells located in the ureteropelvic junction (UPJ) and regulate the peristalsis in this region. Paucity of these cells may be one of the causative factors for congenital UPJO although there is no clear consensus on this issue. Therefore, the present study has been carried out to ascertain the role of ICC as one of the possible etiological factors for congenital UPJO. The aim of this study is to first identify the presence of ICC at UPJ, second to compare the average number of ICC in congenital UPJO with a control population without UPJO, and third to ascertain whether any correlation exists between the number of ICC and postoperative improvement in function of the affected kidney. Materials and Methods: A total number of 30 patients who underwent dismembered Anderson-Hynes pyeloplasty for congenital UPJO between June 2016 and November 2017, were compared with seven controls who underwent nephroureterectomy for various other reasons. The specimen was subjected to immunohistochemistry (IHC), and a quantitative comparison was made for the ICC between cases and controls. The preoperative and postoperative function was evaluated by renal diuretic scintigraphy. Results: The disease was more common among males in the ratio of 6.5:1, and there was a predominance of the left-sided involvement. In the studied cases, the average number of ICC seen for every high-power field (hpf) was 4.86 ± 0.76/hpf, whereas in control it was 11.74 ± 0.86/hpf (P = 0.04). The postoperative outcome, as measured by the improvement in split renal function, did not have any correlation with the number of ICC. Conclusion: The ICC are present at the UPJ and can be detected by immunohistochemistry due to their CD117 positivity. These cells are significantly low at this site in cases of congenital UPJO when compared to controls without any obstruction. The number of ICC bears no correlation to the postoperative improvement in function.

Context: Aggressive periodontitis is a type of inflammatory response in periodontal tissues that is differentiated from chronic by its earlier onset, its high rate of progression, subgingival microbial composition, the difference in the host's immune response, and family history of the disease. Mast cells live in tissues and contribute to the various allergic and inflammatory conditions, including periodontal diseases, through the release of cytokines, chemokines, and proteolytic enzymes. CD117, the receptor of the stem cell factor expressed by the mast cells, is the hallmark of mast cell development. This study aimed to determine the expression level of CD117 in the mast cells of aggressive periodontitis using immunohistochemistry. Aims: This study aimed to determine the expression level of CD117 in the mast cells of aggressive periodontitis using immunohistochemistry. Subjects and Methods: The study was conducted on tissue samples from 15 patients with aggressive periodontitis and 15 patients with healthy gingival tissue. Samples were stained for CD117 markers using immunohistochemistry. After the microscopic examination of samples, all data were entered into SPSS 20 and analyzed. Statistical Analysis Used: Statistical data were analyzed using Kolmogorov–Smirnov test and independent t- test. Results: According to the results, the mean expression levels of CD117 in the aggressive periodontitis and normal gingival groups were 19.08 ± 6.9 and 18.2 ± 8.1, respectively, which were not statistically significant (P = 0.75). The Kolmogorov–Smirnov test verified the normality of distribution of CD117 expression level. Given the normal distribution of the scores, the independent t-test was used to compare the CD117 expression level in the two study groups. Conclusions: There was no significant difference in the level of CD117 expression between the control and aggressive periodontitis groups.

Molecular-based subclassifications of breast cancer are important for identifying treatment options and stratifying the prognosis in breast cancer. This study aimed to assess the prognosis relative to disease-free survival (DFS) and overall survival (OS) in patients with triple-negative breast cancer (TNBC) and other subtypes, using a biomarker panel including cytokeratin 5 (CK5), cluster of differentiation 117 (CD117), and epidermal growth factor receptor (EGFR). This cohort–case study included histologically confirmed breast carcinomas as cohort arm. From a total of 894 patients, 572 patients with early breast cancer, sufficient clinical data, and archived tumor tissue were included. Using the immunohistochemical markers CK5, CD117, and EGFR, two subgroups were formed: one with all three biomarkers negative (TBN) and one with at least one of those three biomarkers positive (non-TBN). There were significant differences between the two biomarker subgroups (TBN versus non-TBN) in TNBC for DFS (p = 0.04) and OS (p = 0.02), with higher survival rates (DFS and OS) in the non-TBN subgroup. In this study, we found the non-TBN subgroup of TNBC lesions with at least one positive biomarker of CK5, CD117, and/or EGFR, to be associated with longer DFS and OS.

The study aimed to evaluate the effects and relationships between mast cells in the matrix, mast cell enzymes tryptase and chymase, epithelial proliferation, microvascular density, and bone destruction in cholesteatoma. Thirty-five biopsies diagnosed with cholesteatoma and seven healthy skin tissues taken from the retro-auricular region for control were evaluated. Immunohistochemical studies were performed with CD117, CD34, Ki-67, chymase, and tryptase antibodies, in a single session for all cases and the control group. The relationship between erosion size and antibody load was determined. The mean cholesteatoma epithelium Ki-67 was higher than the control group (p < 0.001). CD117-positive mast cells, chymase-positive mast cells, tryptase-positive mast cells, and microvessel density were significantly higher in the cholesteatoma matrix compared to the control group (p < 0.002, p < 0.001, p < 0.005). In the group with bone erosion scores of two and above, immunohistochemical markers tended to be higher. A positive correlation was found between CD117 and chymase, tryptase, and microvessel density; between tryptase, chymase, and microvessel density; and between chymase and microvessel density. CD117-positive mast cells and chymase-positive mast cells stimulate angiogenesis, increase the epithelium’s proliferative capacity in the cholesteatoma matrix, and form cholesteatoma. The increased proliferation of cholesteatoma epithelium and increased vascular density in the matrix exacerbate bone erosion.

Background: Odontogenic lesions contain mast cells (MCs), particularly those with a cystic appearance. Because of their high recurrence rates and aggressive clinical behaviour, odontogenic keratocysts (OKCs) require special treatment. A particular kind of protein called cluster of differentiation (CD) 117/ receptor tyrosine kinase (c-KIT) is present on the surface of many cells. Most hematopoietic cells lose their expression of KIT during the differentiation process, with the exception of MCs, which continue to express KIT throughout their lifetime., Aim: Using the CD117 immunomarker, this immunohistochemical investigation sought to assess the presence and location of MCs in OKCs and examine the relationship between MC numbers in sporadic, syndromic, and recurrent OKCs., Methods: The study comprised 30 paraffin-embedded tissue specimens, and a histopathological diagnosis was made from hematoxylin and eosin-stained sections with a thickness of 4-5 µ. Out of 30 specimens, 21 were sporadic, six were recurrent OKCs, and three were syndrome-associated OKCs. CD-117/c-kit rabbit polyclonal primary antibody was used to stain the sections for observing MCs, which were then viewed under a light microscope with a digital camera and a desktop computer with MICAPS software for viewing images., Result: To compare the number of MCs among OKCs, a one-way ANOVA test was used. Our study revealed that a statistically significant increase in MCs has been observed in the subepithelial and deep connective tissue of recurrent OKC (p < 0.05). However, a comparison of the mean MC value among three OKC subtypes did not reveal any statistically significant differences. An increased mast count was observed in the deep connective tissue layer of syndromic OKC under multiple comparisons., Conclusion: Our study concluded that MCs were present in increased numbers both in the superficial and deep connective tissue of recurrent OKCs, indicative of their aggressive clinical behaviour. Increased mean MC counts observed in some of the sporadic cases may be an indicator of their chances of recurrence in the future., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Government Dental College issued approval IEC/221/2021/DCC, dated 5.10.2021. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Varma et al.)

Although intraductal oncocytic papillary neoplasm (IOPN) was considered distinct from the intraductal papillary neoplasm of the pancreas, the oncocytic histologic type remained as a subtype of intraductal papillary neoplasms of the bile duct (IPNBs) with gastric, intestinal, and pancreatobiliary types based on the fifth edition of the WHO classification. To test the characteristics of the oncocytic type of IPNBs, the histopathologic, immunohistochemical (Hep Par-1 and CD117), and clinical characteristics of 13 oncocytic type were compared with 114 others (15 gastric, 39 pancreatobiliary, and 60 intestinal) IPNB types. The oncocytic type, which occupied about 9% of IPNBs, was more frequent in females (p < 0.05) and larger (mean, 5.3 vs. 3.6 cm; p < 0.002) than other IPNB types. Immunohistochemically, the oncocytic type had more frequent combined Hep Par-1 and CD117 expression than other IPNB types (all p < 0.05). The recurrence-free survival rate for patients with the oncocytic type (5-year survival, 100%) was significantly higher (p = 0.015) than for those with other histologic types (59.9%). The oncocytic type had distinct histopathologic, immunohistochemical, and survival outcomes from other IPNBs. Therefore, it can be separated from other IPNB types and classified as one independent entity, similar to IOPN of the pancreas., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The aim. To clarify all most important immunohistochemical features of gastrointestinal stromal tumors with different histological patterns and analyze the role of expression of Ki-67, MMP-9, VEGF and p16ink4A as a predictive markers of tumor progression. Materials and methods. The study is based on analysis of 100 primary GISTs for description of their morphological features and 36 GISTs taken from this 100 for study of prognostic markers. Results. All spindle cell GISTs have shown diffuse expression of CD117 in tumor cells. The levels of CD117 expression varied from strong expression (3+) until mild expression (1+). Strong expression were seen in 75.8 % of spindle cell GISTs. Epithelioid GISTs demonstrated heterognous moderate or mild expression of CD117. All primary epithelioid GISTs from patients that had relapse of tumor in period from 1 till 3 years demonstrated focal mild expression of CD 117 in tumor cells. Expression of DOG-1 were seen in all 100 cases of GISTs, that were included in our study. The strong expression of DOG-1 (3+) were seen in all 45 GISTs that had low mitotic rate (= 5 mitoses per 50HPF) and not associated with their histological pattern. GISTs with high mitotic rate demonstrated heterogeneous expression of DOG-1 in tumors: moderate expression (2+) with patchy areas of strong expression (3+). Expression of CD56 was not found in spindle cell GISTs, but single tumor cells of epithelioid GISTs that had high mitotic rate demonstrated expression of this marker. The average expression of p16ink4A were higher in tumors that gave relapses compared with tumors without relapses (50.3 % versus 5.7 % respectively, U-test = 16.5; p = 0.01). The average expression of MMP-9 also were significantly higher in GISTs that gave relapses: 63.2 % compared with 13.4 % in GISTs without relapse (U-test = 16; p = 0.01). The strong VEGF expression was found in 66.7 % of GISTs that had relapses and only in 8.3 % of GISTs without relapses. 50 % of GISTs without relapses was negative for VEGF. Finally, the average expression of Ki-67 were 13.4 % in GISTs with relapses and 8.7 % in GISTs without them (U-test = 16; p = 0.01). Conclusion. We highly recommend using DOG-1 for epithelioid GISTs. Additionally in epithelioid GISTs can be used CD56 that can give focal positive reaction in some tumour cells. The following minimal panel of markers for differential diagnosis of spindled GISTs from other mesenchymal tumors of gastrointestinal tract is proposed: CD117, DOG-1 and SMA, where the first too markers will demonstrated the moderate or strong diffuse expression and SMA can be occasionally positive in some tumor cells. p16ink4A, Ki-67, VEGF and MMP-9 can be used as additional prognostic markers in GISTs. [ABSTRACT FROM AUTHOR]

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The prognostic significance of internal tandem duplication (ITD) mutations in exons 8 and 11 of c-kit has been well-described for canine cutaneous mast cell tumors (MCTs), but c-kit mutations have rarely been reported in subcutaneous MCTs. The objective of this study was to identify the prevalence of ITD mutations in exons 8 and 11 of c-kit in canine subcutaneous MCTs and to investigate its association with histologic grade, KIT pattern, and proliferation markers. ITD mutations in exons 8 and 11 of c-kit, mitotic count, Ki67 index, AgNOR number, Ki67xAgNOR score, KIT pattern, and histologic grade (two-tier system) were retrospectively recorded for 216 dogs with subcutaneous MCTs. ITD mutations in exons 8 and 11 of c-kit were detected in 23 (10.6%) and 12 (5.56%) subcutaneous MCTs, respectively. Exon 11 mutations were significantly associated with Kiupel high grade (p < 0.001) and increased mitotic count (p < 0.001) compared to subcutaneous MCTs with no mutations in exons 8 or 11 (p = 0.002) or subcutaneous MCTs with a mutation in exon 8 (p = 0.001). There was no significant association of either c-kit mutation with KIT patterns or proliferation activity. This study identified a higher prevalence of ITD mutations in exons 8 and 11 of c-kit in subcutaneous MCTs than previously reported. Like their cutaneous counterpart, subcutaneous MCTs with exon 11 mutations were more likely to be histologically high grade and have a higher mitotic count, whereas such associations were not observed in subcutaneous MCTs with exon 8 mutations.

Mast cell tumors (MCTs) are well-known neoplasms derived from either mucosal or connective tissue mast cells. While well studied in several domestic species, MCTs are rarely documented in rodents. A three-year-old, male African dormouse (Graphiurus sp.) presented with a history of vomiting and anorexia for 3 months. Sonography revealed thickened gastric mucosa and hyperperistalsis. The patient died after receiving symptomatic treatment for 2 months. At necropsy, locally extensive, pale, thickened mucosal foci obscuring the first half of the stomach lumen was noted. Histological examination revealed moderately polymorphic, round, oval to spindle cells with amphophilic cytoplasmic granules infiltrating the mucosa to tunica muscularis, with moderate numbers of eosinophils. The mucosa was severely ulcerated with the proliferation of granulation tissue. The granules in most tumor cells exhibited metachromasia with the toluidine blue stain. Neoplastic cells revealed positive membranous immunoreactivity to KIT. Herein, we report the first case report of MCT in dormouse but also the first gastrointestinal MCT in a rodent species.

c-Kit mutations have been reported in 15% to 40% of certain human melanoma subtypes, including those histologically similar to canine oral malignant melanomas. Therapeutic response to tyrosine kinase inhibitors has been demonstrated in those human patients. As canine oral malignant melanomas tend to have a poor prognosis despite aggressive surgical removal, evaluation of KIT expression and identification of c-Kit mutations in canine oral melanocytic neoplasms was performed to determine if there is any indication that tyrosine kinase inhibitor drugs might effectively treat any of these cases. This study evaluated 27 canine oral malignant melanomas and 12 canine histologically well-differentiated oral melanocytic neoplasms for activating c-Kit mutations, determined differences in immunohistochemical expression of KIT and c-Kit mutation status, and determined if KIT expression could predict c-Kit mutation status. Among samples that contained intraepithelial nests of neoplastic melanocytes in the KIT-labeled sections, KIT was expressed within cells in these nests in 22/23 (96%) malignant melanomas and 5/7 histologically well-differentiated neoplasms. KIT was expressed in 10% to 30% of neoplastic melanocytes in the lamina propria in 3/24 (13%) malignant melanomas, but 0/9 (0%) histologically well-differentiated neoplasms. Next-generation sequencing identified 85 variants in c-Kit, including 9 nonsynonymous mutations that resulted in amino acid changes predicted to affect protein function. c-Kit mutations with predicted deleterious protein effects were more common in malignant melanomas (8/27 [30%] vs 1/12 [8%]). There was no apparent relationship between detected c-Kit mutations and KIT expression. These results do not support the use of therapies that target c-Kit. [ABSTRACT FROM AUTHOR]

Background: Advanced breast cancer (BC) impact immune cells in the blood but whether such effects may reflect the presence of early BC and its therapeutic management remains elusive.Methods: To address this question, we used multiparametric flow cytometry to analyze circulating leukocytes in patients with early BC (n = 13) at the time of diagnosis, after surgery, and after adjuvant radiotherapy, compared to healthy individuals. Data were analyzed using a minimally supervised approach based on FlowSOM algorithm and validated manually.Results: At the time of diagnosis, BC patients have an increased frequency of CD117+CD11b+ granulocytes, which was significantly reduced after tumor removal. Adjuvant radiotherapy increased the frequency of CD45RO+ memory CD4+ T cells and CD4+ regulatory T cells. FlowSOM algorithm analysis revealed several unanticipated populations, including cells negative for all markers tested, CD11b+CD15low, CD3+CD4-CD8-, CD3+CD4+CD8+, and CD3+CD8+CD127+CD45RO+ cells, associated with BC or radiotherapy.Conclusions: This study revealed changes in blood leukocytes associated with primary BC, surgical removal, and adjuvant radiotherapy. Specifically, it identified increased levels of CD117+ granulocytes, memory, and regulatory CD4+ T cells as potential biomarkers of BC and radiotherapy, respectively. Importantly, the study demonstrates the value of unsupervised analysis of complex flow cytometry data to unravel new cell populations of potential clinical relevance. [ABSTRACT FROM AUTHOR]

Plasma cell leukemia (PCL) is a rare (1-2 %) aggressive plasma cell dyscrasia (PCD) with a poor prognosis and characterized by the presence of more than 20% circulating plasma cells (PCs). Multicolor Flowcytometry is used for differentiating PCs in PCL. In this study, we aimed to compare the clinical, laboratory findings and immunophenotypic profiles of patients with PCL. A total of 512 patients were investigated for PCD in our hospital between 2011-2019. The immunophenotypic profile (including, CD27, CD28, CD38, CD138, CD45, CD117, CD19, CD20, CD56, CD33, CD81, and ckappa/clambda,) were evaluated retrospectively. The clinical findings, pathology reports, immunofixation electrophoresis and MFC results of three patients with PCL were reevaluated using 6 color multiparametric flow cytometry (MFC). Only three patients were diagnosed as PCL. PCs population defined by the co-expression of CD38 and CD138 was observed as 50%, 53%, 60%, respectively. Expression of each CD56, CD117, CD20, CD45 was seen in individual cases. CD19 was negative in all cases. Cytoplasmic kappa light chain expression was detected only in one case. Two of the cases were primary and the other was secondary PCL. Bortezomib-based treatment was initiated. Overall survival of primary PCL cases were 24 months and 6 months, whereas secondary PCL was four months. Co-expression of CD38 and CD138 in identifying PCs with MFC may be considered the best combination and leads to early diagnosis within hours and appropriate treatment in patients with PCL. [ABSTRACT FROM AUTHOR]

It is well-known to pathologists that melanoma is “the great mimicker” and can look like anything. Despite this widespread awareness, the diagnosis remains a continuous challenge, especially when a metastatic melanoma with rare morphology is examined. We report a case of a 64-year-old man with a lung mass and right-sided pleural effusion who underwent video-assisted thoracoscopic surgery for pleural decortication. The history of melanoma was not reported to us. Microscopic examination revealed sheets of small round blue cells infiltrating into the adipose tissue in a lace-like pattern mimicking lymphoblastic lymphoma. Immunohistochemical stains for melanocytic markers, including S-100 protein, Mart-1, and HMB-45, highlighted the neoplastic cells. The tumor was also positive for CD56 and CD117, but negative for pancytokeratin, CD45, cytokeratin 8, TTF-1, WT1, CD34, chromogranin, synaptophysin, and neuron-specific enolase. The findings were most consistent with metastatic small cell melanoma, an uncommon variant of melanoma that closely resembles lymphoblastic lymphoma and other malignant small round blue cell tumors. To our knowledge, we are the first to describe a case of metastatic small cell melanoma to the pleura in an adult. Clinical and histological details are provided with a review of the literature.

The aim of this research was to investigate the clinical role and prognostic value of CD117 expression assessed immunohistochemically in lung carcinoma through a comprehensive meta-analysis in which 27 publications were acquired and 2645 patients were ultimately analysed. Statistical analysis and corresponding plots were performed using STATA version 12.0. Publication bias was assessed by Begg’s funnel plots and Egger’s test. Pooled HR and its 95% CI (HR = 1.53, 95% CI: 1.13-2.07, p = 0.007) for overall survival of patients indicated a poor prognostic value for CD117 expression in lung carcinoma, which was accompanied by heterogeneity and publication bias. In the subgroup analysis, there was strong evidence that could support an association between CD117 expression and poor prognosis in NSCLC patients (HR = 2.03, 95% CI: 1.41-2.90, p