The High-Grade Glial Component Of Pediatric Primary Anaplastic Ganglioglioma Characterized Astroblastoma-Like Pseudorosettes With BRAFV600E Mutation And Deletion Of CDKN2A/B, PTEN, And BMPR1A: A Case Report

Background: Ganglioglioma (GG) is a low-grade mixed neuronal-glial tumor which is the most common type of long-term epilepsy-associated tumors (LEATs). However, primary anaplastic ganglioglioma (AGG) which composes of malignant changes is rare. Here, we report a case of pediatric primary AGG which is consisted of low-grade/begnin GG and high-grade glioma that was characterized by astroblastoma-like pseudorosettes. Case presentation: We describe a case of 4-year-old female who presented with medically refractory seizure for 14 months by a temporal mass. The patient underwent a gross total mass resection at the first surgery, and was only treated with antiepileptic therapy and followed by observation. After nine months, tumor recurrence was found. Followed by second operation, the patient was treated with chemotherapy (oral temozolomide and antiepileptic drugs) and local radiotherapy. At 58-month follow-up after the second operation, no epileptic seizures and tumor recurrence were found again. In the first sample, the tumor contained two different components. The major component presented the low-grade GG’s features of neoplastic glial cells and dysplastic ganglion cells. The minor component was a heterogeneous high-grade glioma characterized astroblastic-like pseudorosettes clusters with increased mitotic figure (about 4-6 per 10 high-power fields). CD34 staining was negative. BRAFV600E was positive in both components. In the recurrent sample, the heterogeneous high-grade glioma became the major component. The fuorescence in situ hybridization (FISH) of MN1 break-apart probe and MYB–QKI fusions probe were negative. BRAFV600E mutation, and deletion of CDKN2A/B, PTEN and BMPR1A were detected by targeted DNA sequencing. Conclusion: This case extends the histomorphologic spectrum and enriched genetic features of primary AGG in childhood. The high-grade glioma charactered astroblastoma-like pseudorosettes may be an important cause of tumor recurrence in a short period of time. Tumor gross total surgical resection and adjuvant chemoradiotherapy were important to achive an event-free survival.

Malignant Glomus Tumor of the Kidney: A Case Report and Review of the Literature

Introduction/Objective Glomus tumors are rare neoplasms arising from the glomus body which is a specialized arteriovenous anastomosis that has a role in temperature regulation of the skin. They account for less than 2% of soft tissue tumors and typically manifest as painful nodules in the extremities, most commonly in the subungual region of the fingers and dermis of the wrist, forearm, and foot. They rarely arise in visceral organs as they lack glomus bodies. There are rare case reports of benign glomus tumors arising in the kidney, and malignant renal glomus tumors are exceedingly rare. Methods/Case Report We present a case of a 32-year-old man who was found to have a right renal mass incidentally after being involved in a motor vehicle accident. Computed tomography of the abdomen revealed a 5.3 cm enhancing mass in the posterior aspect of the inferior pole of the right kidney. Histological examination revealed a solid neoplasm composed of a pleomorphic population of cells with densely eosinophilic to pale cytoplasm, centrally located round to oval nuclei with fine nuclear chromatin and relatively inconspicuous nucleoli. Prominent lymphovascular invasion and 1 mitotic figure per 10 high power fields were also present. Areas composed of necrosis, sclerosis, hemosiderin deposition and calcification were identified. Immunohistochemical stains revealed the neoplastic cells to be positive for CD34, vimentin, smooth muscle actin, caldesmon, with focal reticulin staining around the tumor cells. Cells were negative for desmin, high and low molecular weight cytokeratins, synaptophysin, chromogranin, PAX8, and GATA3. The morphology and immunoprofile of the mass are consistent with the diagnosis of glomus tumor. Results (if a Case Study enter NA) NA Conclusion Although very rare, the presence of prominent vascular invasion, increased mitotic activity as well as necrosis are consistent with malignant behavior and support the classification as a malignant glomus tumor.

The long-term outcome of gastrointestinal stromal tumors treatment

Background: To evaluate the overall survival, disease free survival, clinicopathological characteristics and prognostic factors of patients with gastrointestinal stromal tumors (GISTs) who were treated at Faculty of Medicine Vajira Hospital. Methods: A retrospective review data of 39 GISTs patients who underwent surgery at Vajira hospital from 2007 to 2011 was performed. The patient characteristics, overall survival, disease-free survival of patients and prognostic factors were evaluated. Results: The median age of patients was 60 years (22-90 years), 54% were female and the main presenting symptom was abdominal pain (33%). Stomach (62%) and small intestine (30%) were the most common locations of tumor respectively. Complete resections (R0) were performed in 31 patients (80% ). All patients (100%) were positive for CD117 and 84.6% for CD34. According to the Armed Forces Institute of Pathology criteria, 56.4% of patients were characterized as a high risk. With a median follow-up time of 46 months (1-139 months). The overall survival and disease-free survival at 5 years were 84.6% and 66.7%, respectively. Two patients received Imatinib in neoadjuvant setting while 10 patients for disease control. Eight patients (20.5%) developed recurrences. R0 resection, mitotic figure and location of tumor were the significant prognostic factors. Conclusions: The overall survival and disease-free survival at 5 years were 84.6% and 66.7%, respectively. R0 resection, mitotic figure and location of tumor were the significant prognostic factors. Keywords: gastrointestinal stromal tumor; gists; prognostic factors; survival.

The Relationship Between Epidermal Mitotic Density, Atypical Mitotic Figure Density, Breslow Depth, Ulceration, and Dermal Mitotic Rate in Cutaneous Melanoma: A Retrospective Cohort Study

Prognostic factors for melanoma include Breslow depth (BD), ulceration, and dermal mitotic rate (DMR). No studies have queried the effect of epidermal mitotic density (EMD) or atypical mitotic figure density (AMD) in an outcome-based assessment. Our objective was to determine if there is a relationship between EMD, AMD, BD, DMR, and ulceration and patient outcomes. This was a retrospective cohort study of 185 cases of thick and thin melanomas. Univariate and multivariate cause-specific regression analysis was performed. There was a positive correlation between EMD and BD ( P = .0001). The difference between AMD in thick and thin melanomas was statistically significant. For every unit increase in EMD, patients had a 2.8-fold increase in the risk of distant metastasis; however, statistical significance was lost in the multivariate analysis. In adjusted analyses, ulceration, DMR, and BD were associated with outcomes. There were no statistically significant correlations between AMD and outcomes. This study is limited by its small sample size, diminution of the epidermis in some thick melanomas preventing EMD estimates, and reproducibility of mitotic figure counting. EMD and AMD do not seem to have any independent value in multivariate analyses for melanoma. Ulceration, BD, and DMR were significantly associated with outcomes and further solidify these known predictors of prognosis.

Primary Splenic Pleomorphic Liposarcoma in a Bitch

Background: Liposarcoma is a malignant neoplasm of lipoblasts with low incidence in dogs, representing 1.7% of neoplasms diagnosed in the spleen. In veterinary medicine, this neoplasm is classified morphologically into the myxoid, well-differentiated, undifferentiated and pleomorphic subtypes, the latter being one of the most aggressive forms, mainly in cavity organs. This study reports a case of primary splenic pleomorphic liposarcoma in a female dog, addressing anatomopathological and immunohistochemical aspects.Case: A 14-year-old, 35 kg female mongrel canine with a history of absence of defecation, progressive weight loss, difficulty walking, sensitivity to abdominal palpation, prostration, pale mucous membranes, tachypnea and abdominal distention. The condition evolved to death and, on necroscopy, there was an increase in splenic volume with neoformation of whitish and reddish color, measuring 32 × 27 cm in its largest axes and weighing 8.9 kg. The neoformation exhibited areas of firm and soft consistency, and sectioning revealed the existence of focal areas of extensive necrosis and cavity collections of different diameters that allowed the flow of liquid serous contents with a brownish red color. Microscopy showed cells of neoplastic morphology infiltrating the splenic parenchyma, mostly with slightly acidophilic cytoplasm and few intracytoplasmic lipid vacuoles, which varied in size and distribution. The nuclei of the cells were large, eccentric and irregular, with round to oval morphology, grossly lacy chromatin and single or multiple evident nucleoli. These cells exhibited marked anisocytosis, anisokaryosis and pleomorphism, with more than one mitotic figure per high magnification field visible. Moderately inflammatory infiltrate, predominantly lymphocytic, permeated the neoplastic cells, and marked depletion of lymphoid follicles and atrophy of the red pulp were found in the remaining splenic parenchyma. Immunohistochemical tests revealed marked and discrete immunostaining for anti-vimentin and anti-S100 antibodies, respectively. No staining was observed for anti-pan cytokeratin, anti-desmin, anti-alpha smooth muscle actin or anti-CD20 antibodies. Based on anatomopathological and immunohistochemical aspects, it was concluded to be a splenic pleomorphic liposarcoma of primary origin.Discussion: the spleen is not a common anatomical site for the development of liposarcoma, a neoplasm whose origin remains unclear. Similar to what occurs in humans, liposarcoma is believed to develop from the adipose tissue of the splenic hilum. Thus, it should be considered as a differential diagnosis of invasive abdominal tumors. For the identification and classification of liposarcoma as a pleomorphic subtype, we considered mainly histological findings such as marked cell atypia and intracytoplasmic lipid vacuoles, which may or may not be present in neoplastic cells. Immunohistochemical examination favored the diagnosis of liposarcoma, regardless of the subtype, due to the marked immunostaining for the anti-vimentin antibody, unlike immunostaining for the anti-S100 antibody, for which it was variable. This fact is related to adipocyte differentiation, where lower amounts of intracytoplasmic lipids translate into lower immunostaining intensity for anti-S100. Histological and immunostaining aspects should be regarded with caution in the diagnosis of pleomorphic liposarcoma, as it is a distinct neoplastic entity, with a complex karyotype and without correlation with the other subtypes.

Cellular Testicular Fibroma of Gonadal Stroma with Extensive Myoid Differentiation: A Mimicker of Testicular Leiomyoma

Fibroma of the testis is a rare benign Sex Cord Stromal Tumour (SCST) of probable gonadal stromal origin, occurring in adult males. Characterised by slow and insidious growth, it is devoid of hormonal association and serum markers. Clinically, it can mimic seminoma and requires histopathological examination for identification. Microscopic characteristics include hypercellular spindle cell areas and hypocellular hyaline plaques. Authors report a case of a 41-year-old male presenting with complaints of lower abdominal pain and dysuria. Ultrasonography (USG) showed enlarged left testis with heterogenous echotexture. With a clinical diagnosis of testicular tumour, orchidectomy was performed. Histology showed a well circumscribed, encapsulated cellular neoplasm comprising of spindle and fusiform cells in fascicles, nodules and bundles. The cells showed fusiform vesicular nuclei and eosinophilic cytoplasm, focal epithelioid cells with grooved nuclei and occasional mitotic figure. Stromal collagen fibres and hyalinisation were noted. Testicular tissue was seen compressed peripherally. The tumour cells demonstrated positive reactivity for Smooth Muscle Actin (SMA), h-Caldesmon and inhibin, negative for S-100 and CD34 (Cluster of Differentiation) on Immunohistochemistry (IHC). Literature review helped in arriving at a diagnosis of cellular Testicular Fibroma (TF) with myoid differentiation. Testicular spindle cell lesions are rare, and comprise of different entities, one of which is TF. Histology and IHC are useful aids in diagnosis. Awareness of the differential diagnosis and the IHC markers can help in arriving at a conclusive diagnosis.

Gross and Histopathological Study of the Genitalia in Goats: 2. Tubular Genital Organs (Uterine tubes and Uterus)

The aim of this study was to detect the microscopic and macroscopic lesions in uterine tubes and uterus in Sluaimani abattoir, Kurdistan region/Iraq. The total samples collected were 340 genitalia of does of pregnant and non-pregnant. 37.05% (126/340) of the samples were pregnant and 37.35% (127/340) of the samples were observed without gross lesions and 2.23% (10/340) were noticed with uterine tube gross abnormalities and the remaining 34 (12.941%) samples were recorded as anatomical lesions and pathological lesions of uterus. The a numbers of uterine tubes abnormalities were 11 out of 340 specimens (3.235%), and the most common lesions were; salpingitis 6 cases (7.64%); 1 case from each of hydrosalpinx and Pyosalpinx, respectively (0.294%). Microscopically, the lesions of salpingitis were sloughing off the part of the epithelium and infiltration of inflammatory cells. Three specimens of cyst on uterine tubes (0.882%). The numbers of uterine lesions were 44 specimens which shared 12.941% of abnormalities out of the 340 collected specimens. The most common diseased genital cases were; endometritis and metritis which 21 cases (6.176%), which were histopathologically characterized by a significant increase in the endometrial thickness due to diffuse infiltration of inflammatory cells mainly lymphocytes, the proliferation of fibroblasts with deposition of extracellular matrix. Five pyometra (1.470%), which was histolopatholgically characterized by definite increase in the uterine wall thickness, especially in the endometrium due to infiltration of light pinkish fibrinous inflammatory exudates with mild inflammatory cell proliferation. Three Hydrometra specimens (0.882%), and five endometrial cystic hyperplasia (1.470%). The microscopic lesions for them include massive cystic dilatation of the uterine gland that contains pinkish granular secretion, infiltration of light pinkish edematous fluid in the endometrial stroma associated with inflammatory cells. Two specimens of uterine wall with cysticercus tenuicolis (0.588%), and one uterine melanoma (0.294%), The histopathological features for the uterine melanoma include; deposition of the dark black melanin pigment within the phagocytic cells. Uterine leiomyosarcoma was one specimens (0.294%), which histologically, appear as pleomorphic cells variable in shape and size with different nuclear size randomly oriented in different directions, some of these cells were hyperchromatic with an abnormal mitotic figure. One case of cyst on the uterine wall was found (0.294%), and five cervicitis (1.470%). Finally, it could be concluded that uterine tubes, and uterus abnormalities constitute a percentage (3.235%, and 12.941%), respectively. In this study, uterine melanoma, and uterine leiomyosarcoma were firstly recorded in this study in Iraq and Kurdistan region.

Deep learning algorithms out-perform veterinary pathologists in detecting the mitotically most active tumor region

Manual count of mitotic figures, which is determined in the tumor region with the highest mitotic activity, is a key parameter of most tumor grading schemes. It can be, however, strongly dependent on the area selection due to uneven mitotic figure distribution in the tumor section. We aimed to assess the question, how significantly the area selection could impact the mitotic count, which has a known high inter-rater disagreement. On a data set of 32 whole slide images of H&E-stained canine cutaneous mast cell tumor, fully annotated for mitotic figures, we asked eight veterinary pathologists (five board-certified, three in training) to select a field of interest for the mitotic count. To assess the potential difference on the mitotic count, we compared the mitotic count of the selected regions to the overall distribution on the slide. Additionally, we evaluated three deep learning-based methods for the assessment of highest mitotic density: In one approach, the model would directly try to predict the mitotic count for the presented image patches as a regression task. The second method aims at deriving a segmentation mask for mitotic figures, which is then used to obtain a mitotic density. Finally, we evaluated a two-stage object-detection pipeline based on state-of-the-art architectures to identify individual mitotic figures. We found that the predictions by all models were, on average, better than those of the experts. The two-stage object detector performed best and outperformed most of the human pathologists on the majority of tumor cases. The correlation between the predicted and the ground truth mitotic count was also best for this approach (0.963–0.979). Further, we found considerable differences in position selection between pathologists, which could partially explain the high variance that has been reported for the manual mitotic count. To achieve better inter-rater agreement, we propose to use a computer-based area selection for support of the pathologist in the manual mitotic count.

Large Solitary Luteinized Follicle Cyst of Pregnancy and Puerperium: a Rare Post-partum Clinical Presentation

Introduction/Objective In literature, all large solitary luteinized follicular cysts of pregnancy and puerperium (LSLFCPP) recognized were removed before or during delivery. This would be the first case in literature describing the clinical behavior of the LSLFCPP in the post-partum period. Methods We herein report a rare case of 21-year-old G2P2 female who underwent a full-term uneventful spontaneous vaginal delivery (39w0d, APGARS 9,9) without removal of the undiagnosed LSLFCPP, which nearly doubled in size post-partum. Her past medical history was significant for treated syphilis and normal Pap Test of the cervix. Three months after delivery, the patient presented with LSLFCPP exhibiting mass effect (retroverted uterus, mild right-sided obstructive uropathy, compressed bladder and intermittent pain). The antepartum ultrasound showed 14 cm pelvic mass that had grown to 30 cm on CT scan, in largest dimension. Beta-hCG levels returned to pre- pregnancy levels. Treponema pallidum antibody, FTA-ABS and RPR were reactive. Alpha-fetoprotein, inhibin B, CA- 125, CEA, and CA 19-9 screen were unremarkable. The patient underwent exploratory laparotomy cyst removal with right salpingo-oophorectomy. Results Grossly, the tumor weighed 22 lbs with a diameter of 28 cm; excrescences were not noted. Intraoperative consultation revealed a unilocular benign cyst. Histologically, the cyst was not only lined by luteinized cells but nests of luteinized cells infiltrated the fibrous wall. These cells were positive for Inhibin A and calretinin. A rare mitotic figure was noted. A diagnosis of LSLFCPP was rendered. Conclusion High levels of gonadotropin in pregnancy are implicated in the pathogenesis of LSLFCPP; however, in our case, the cyst doubled in size three months after delivery with undetectable beta-hCG levels. This indicates that the pathogenesis of this cyst relies on more than beta-hCG stimulation. LSLFCPP is important to recognize because it can mimic a malignant proliferation on frozen section and can potentially compromise fetal viability with mass effect.