Positive Immunohistochemical Staining Research Articles

The risk of PD-L1 expression misclassification in triple-negative breast cancer

PurposeStratification of patients with triple-negative breast cancer (TNBC) for anti-PD-L1 therapy is based on PD-L1 expression in tumor biopsies. This study sought to evaluate the risk of PD-L1 misclassification.MethodsWe conducted a high-resolution analysis on ten surgical specimens of TNBC. First, we determined PD-L1 expression pattern distribution via manual segmentation and measurement of 6666 microscopic clusters of positive PD-L1 immunohistochemical staining. Then, based on these results, we generated a computer model to calculate the effect of the positive PD-L1 fraction, aggregate size, and distribution of PD-L1 positive cells on the diagnostic accuracy.ResultsOur computer-based model showed that larger aggregates of PD-L1 positive cells and smaller biopsy size were associated with higher fraction of false results (P < 0.001, P < 0.001, respectively). Additionally, our model showed a significant increase in error rate when the fraction of PD-L1 expression was close to the cut-off (error rate of 12.1%, 0.84%, and 0.65% for PD-L1 positivity of 0.5–1.5%, ≤ 0.5% ,and ≥ 1.5%, respectively, P < 0.0001). Interestingly, false positive results were significantly higher than false negative results (0.51–22.62%, with an average of 6.31% versus 0.11–11.36% with an average of 1.58% for false positive and false negative results, respectively, P < 0.05). Furthermore, heterogeneous tumors with different aggregate sizes in the same tumor, were associated with increased rate of false results in comparison to homogenous tumors (P < 0.001).ConclusionOur model can be used to estimate the risk of PD-L1 misclassification in biopsies, with potential implications for treatment decisions.

High GILT Expression Is Associated with Improved Survival in Metastatic Melanoma Patients Treated with Immune Checkpoint Inhibition.

Simple SummarySkin cancer is the most common type of cancer, with melanoma being among the deadliest of skin cancers due to its propensity to metastasize. Immune checkpoint inhibitors (ICI) generate anti-tumor immune responses resulting in improved outcomes in patients with metastatic melanoma. However, only a subset of melanoma patients responds to these therapies, which are costly and come with a risk of adverse effects. Therefore, there is a need for biomarkers to predict which patients will respond to ICI. We found that ICI-treated metastatic melanoma patients with high GILT mRNA expression in bulk tumor samples had improved survival. Additionally, high GILT protein expression within metastatic melanoma cells was associated with improved survival in patients treated with ICI. This study suggests that GILT may serve as a biomarker to predict which patients will respond to ICI, which could improve patient care, reduce healthcare costs, and facilitate appropriate selection of therapies for patients with metastatic melanoma.Gamma-interferon-inducible lysosomal thiol reductase (GILT) is critical for MHC class II restricted presentation of multiple melanoma antigens. There is variable GILT protein expression in malignant melanocytes in melanoma specimens. High GILT mRNA expression in melanoma specimens is associated with improved overall survival, before the advent of immune checkpoint inhibitors (ICI). However, the association of GILT in metastatic melanoma with survival in patients treated with ICI and the cell type expressing GILT associated with survival have not been determined. Using RNA sequencing datasets, high GILT mRNA expression in metastatic melanoma specimens was associated with improved progression-free and overall survival in patients treated with ICI. A clinical dataset of metastatic melanoma specimens was generated and annotated with clinical information. Positive GILT immunohistochemical staining in antigen presenting cells and melanoma cells was observed in 100% and 65% of metastatic melanoma specimens, respectively. In the subset of patients treated with ICI in the clinical dataset, high GILT protein expression within melanoma cells was associated with improved overall survival. The association of GILT mRNA and protein expression with survival was independent of cancer stage. These studies support that high GILT mRNA expression in bulk tumor samples and high GILT protein expression in melanoma cells is associated with improved survival in ICI-treated patients. These findings support further investigation of GILT as a biomarker to predict the response to ICI.

Erythematous, telangiectatic nodule within the melomental fold

Erythematous, telangiectatic nodule within the melomental fold

Cystitis Cystica and Cystitis Glandularis of the Urinary Bladder: A Review and Update

Cystitis Cystica and Cystitis Glandularis of the Urinary Bladder: A Review and Update

High-grade myoepithelial carcinoma of the palate and maxillary sinus complex: a case report

<h3>Introduction</h3> Myoepithelial tumors typically arise from myoepithelial cells of salivary glands, however myoep- ithelial tumors arising in the skin and soft tissues have been increasingly recognized. Myoepithelial carcinomas (MC) have been described in each of these anatomic locations. Myoepithelial carcinoma of the salivary gland is a rare neoplasm composed exclusively of myoepithelial cells. The diagnosis of myoepithelial carcinoma is based on establishing the immunophenotype of the cellular proliferation, degree of cytologic atypia, presence of mitoses and necrosis, and exclusion of mimics. The morphologic heterogeneity further complicates the diagnosis of MC. <h3>Case Findings</h3> A 54-year-old woman presented with a progressive enlargement of the left palate, with imaging demonstrating involvement of adjacent maxillary sinus with extension to the floor of the orbit. Histologically, the lesion was characterized by malignant appearing epithelioid and clear cells compactly arranged in confluent sheets with no evidence of ductal differentiation. The sheets of tumor cells had a somewhat lobular architecture demar- cated by thin vascular septa. Nuclear pleomorphism, numerous mitoses, and focal necrosis were present. <h3>Results</h3> Positive immunohistochemical staining of tumor cells with CK7, SOX10, S100, P63, P40, and SMA favored a myoepithelial phenotype. <i>SMARCB1</i> (<i>INI1</i>) was expressed, excluding <i>SMARCB1</i>-deficient sinonasal carcinoma. Neg- ative staining of tumor cells for TTF1, CD20, GFAP, calponin, HMB45, PAX8, CD31, CD34 appear to exclude melanoma, renal cell carcinoma, renal cell like sinonasal carcinoma, thyroid carcinoma, lung carcinoma and PEComa. Outside consultation reported positive P16 but the tumor was negative for high risk HPV, thus excluding HPV related mul- tiphenotypic sinonasal carcinoma. Ki-67 revealed a high proliferative index of 70%. <h3>Conclusions</h3> This study demonstrates the clinical and histopathologic findings of a high-grade myoepithelial carci- noma involving the palate and maxillary sinus complex. Exclusive myoepithelial differentiation (morphologic and immunophenotypic) accompanied by established criteria of malignancy allow for definitive diagnosis of this rare salivary gland tumor.

Determining the Role of Immunohistochemical Expression of CK20 in Grading Urothelial Carcinoma

Background: The cytoskeleton-associated intermediate filaments, CK20 belong to epithelial subgroups and it has a controlled expression in gastrointestinal marked cells and in the urinary tract. During embryogenesis, cytokeratin is the first intermediate filament type and they provide facilitation in maintaining the integrity and mechanical stability of cells. It is identified with regard to neoplastic urothelial cells there is a strong and diffuse cytoplasmic immunoreactivity for CK20 that involve all three layers of the urothelium. Therefore, the aim of the study was to determine the role of the immunohistochemical expression of CK20 in the grading of urothelial carcinoma.&#x0D; Methodology: It was a retrospective cross-sectional study that was conducted at the Department of Histopathology, Lady Reading Hospital, Peshawar, Pathology department, Sheikh Zayed medical college and Hospital, Rahimyar Khan and Khyber Medical college and Khyber Teaching Hospital, Peshawar from March 2021 till September 2021. Ninety-seven, (97) Paraffin-embedded blocks of urothelial carcinoma along with records of these patients, which were collected over three years from January 2018 till December 2020, were retrieved from the archives of the Histopathology departments of these hospitals. These blocks were cut and stained with Hematoxylin Eosin and CK20 antibodies. Expression of CK20 was noted by two consultant pathologists. Positive expression was considered when cytoplasmic immunohistology expression of CK20 was seen in deep layers of the urothelium or diffused strong cytoplasmic staining of urothelial cells beyond the superficial cells was found. Negative expression was defined as CK 20 staining restricted to the superficial cells or Negative expression was defined as CK 20 staining restricted to superficial “Umbrella” cells of urothelium.&#x0D; Results: Out of 97 patients, the minimum age was 20 years and maximum age was found to be 90 years with mean + standard deviation of 64 +11 years. There were 86 (88.6%) male patients and 11 (11.3) female patients. Low grade urothelial carcinoma was seen in 49(51 %) patients while 48 (49%) cases displayed high grade morphology. CK20 was found positive in 74 (76.3%) patients. Among positive cases, 43 cases were high grade and 31 cases were low grade urothelial carcinomas.&#x0D; Conclusion: CK20 Positivity was seen in 76.3% of the patients with papillary urothelial carcinoma. CK20 is an important immunohistochemical marker for early diagnosis and grading of urothelial carcinomas. Positive Immunohistochemistry staining of the urothelial carcinomas were found in high-grade as well as low-grade urothelial carcinomas but in comparison, 43 cases of high-grade urothelial carcinomas had exhibited positive immunohistochemistry staining for CK 20 and 31 cases of low-grade urothelial carcinomas had exhibited positive staining for CK20 which would indicate that perhaps immunohistochemistry staining features of urothelial carcinoma would tend not to completely differentiate between high-grade and low-grade urothelial carcinomas.

The relationship between tumour infiltrating lymphocytes, Epstein-Barr virus and Helicobacter pylori infection in gastric cancer.

ObjectiveEpstein–Barr virus (EBV) and Helicobacter pylori (HP) infections have been extensively recognised as gastric cancer (GC) triggers, and recent publications suggest they could behave as predictive markers for immune-modulating therapies. Tumour-infiltrating lymphocytes (TILs) have also been identified as a predictive biomarker for immunotherapy in different malignancies. This study aimed to investigate the association between EBV and HP infection with TIL levels in GC.MethodsTIL evaluation in haematoxylin-eosin was performed by a pathologist and density of CD3, CD8 and CD163 positive (immunohistochemistry staining) immune cells was calculated with the use of digital pathology software. EBV infection was detected by in situ hybridisation (ISH) and by quantitative polymerase chain reaction (qPCR). Methylation status of EBV-related genes was detected by PCR and a methylome analysis was performed by the Illumina Infinium MethylationEPIC BeadChip. HP status was detected by qPCR.ResultsWe included 98 resected GC Peruvian cases in our evaluation. Median TIL percentage was 30. The proportion of EBV+ detected by ISH was 24.1%, of EBV+ detected by qPCR was 41.8%, while 70% showed methylation of EBV-related genes, and 58.21% of cases were HP+. Younger age (p = 0.024), early stages (p = 0.001), HP+ (p = 0.036) and low CD8 density (p = 0.046) were associated with longer overall survival (OS). High TIL level was associated with intestinal subtype (p < 0.001), with grade 2 (p < 0.001), with EBV qPCR+ (p = 0.001), and with methylation of EBV-related genes (p = 0.007). Cases with high TIL level and cases that are EBV positive share eight genes with similarly methylated status in the metabolomic analysis. High CD8 density was associated with EBV PCR+ (p = 0.012) and HP− (0.005).ConclusionLower CD8 density and HP+ predict longer OS. High TIL level is associated with EBV+ and methylation of EBV-related genes, while lower CD8 density is associated with HP+ GC.

De‐escalation of five‐year adjuvant endocrine therapy in patients with estrogen receptor‐low positive (immunohistochemistry staining 1%‐10%) breast cancer: Propensity‐matched analysis from a prospectively maintained cohort

BackgroundThe standard 5 years of endocrine therapy has demonstrated additional benefits compared with short‐term (2‐3 years) treatment in patients with estrogen receptor (ER)‐positive breast cancer; however, data specific to ER‐low positive breast cancer (1%‐10% by immunohistochemistry) are limited, and it is unclear whether long‐term treatment is still necessary for this subgroup.MethodsThe authors used the prospectively maintained Breast Surgery Database of Fudan University Shanghai Cancer Center for this propensity‐matched analysis. The primary end point was disease‐free survival. Multivariate Cox regression analysis and propensity score‐matching methods were used to minimize bias. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated. All statistics were 2‐sided.ResultsFrom 2012 to 2017, 22,768 consecutive women had pathologically confirmed, early stage breast cancer, and 1013 (4.45%) were identified with ER‐low positive disease. Among these, 634 patients met the inclusion criteria and were divided into 3 groups: those who received no endocrine therapy (n = 89), those who received 2 to 3 years of endocrine therapy (n = 185), and those who received approximately 5 years of endocrine therapy (n = 360). At a median follow‐up of 65 months, there was no significant difference in disease‐free survival between patients who received 2 to 3 years and 5 years of endocrine therapy (HR, 0.82; 95% CI, 0.51‐1.33; P = .43). The findings were consistent after multivariate Cox analysis of the propensity score‐matched samples (5 vs 2‐3 years of treatment: HR, 0.74; 95% CI, 0.41‐1.31; P = .30).ConclusionsShort‐term endocrine therapy for 2 to 3 years might be an alternative for patients who have ER‐low positive breast cancer instead of the standard 5 years of treatment.

K-Ras and p53 mouse model with molecular characteristics of human rhabdomyosarcoma and translational applications.

ABSTRACTRhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children, with overall long-term survival rates of ∼65-70%. Thus, additional molecular insights and representative models are critical for identifying and evaluating new treatment modalities. Using MyoD-Cre-mediated introduction of mutant K-RasG12D and perturbations in p53, we developed a novel genetically engineered mouse model (GEMM) for RMS. The anatomic sites of primary RMS development recapitulated human disease, including tumors in the head, neck, extremities and abdomen. We confirmed RMS histology and diagnosis through Hematoxylin and Eosin staining, and positive immunohistochemical staining for desmin, myogenin, and phosphotungstic acid–Hematoxylin. Cell lines from GEMM tumors were established with the ability to engraft in immunocompetent mice with comparable histological and staining features as the primary tumors. Tail vein injection of cell lines had high metastatic potential to the lungs. Transcriptomic analyses of p53R172H/K-RasG12D GEMM-derived tumors showed evidence of high molecular homology with human RMS. Finally, pre-clinical use of these murine RMS lines showed similar therapeutic responsiveness to chemotherapy and targeted therapies as human RMS cell lines.

Plasmacytoma/multiple myeloma type posttransplant lymphoproliferative disorder.

A 38-year-old male with a history of lupus nephritis and kidney transplantation 3 years ago, presented with fever, night sweats, and lymphadenopathy while being treated with tacrolimus, mycophenolate mofetil, and prednisone. Evaluation with PET and CT scan showed generalized lymphadenopathy and splenomegaly. (Left-sided figure). Biopsy of an inguinal lymph node showed a monotypic plasma cell proliferation (CD138+, kappa+, CD20-), as part of a monomorphic variant of post-transplant lymphoproliferative disease (PTLD) (Right-sided figure). The specific type was determined as plasmacytoma/multiple myeloma type PTLD. However, a diagnosis of PTLD type plasma cell-rich marginal zone lymphoma was also possible, although no separate malignant lymphocytic B-cell component could be demonstrated. No Epstein–Barr virus (EBV) positivity was found. Bone-marrow showed a similar monomorphic PTLD with an increased amount of plasma cells. Laboratory testing showed only mild anemia and no kidney function decline or hypercalcemia. M-protein was identified as IgA-kappa, 24 g/L. There were no bone lesions. Cytogenetics of the bone marrow showed no abnormalities. A diagnosis of plasmacytoma/multiple myeloma type PTLD was made, and treatment was commenced with thalidomide, bortezomib, and dexamethasone. Multiple myeloma/plasmacytoma-like PTLD is a rare complication of solid organ transplant. It is characterized by plasmacytic histology with the presence of CD138 and lack of CD20. Only 3.5% of PTLD are of this subtype [1]. In a retrospective cohort and case series, the median time from organ transplant to disease was 3–10 years [1-4]. Bone lesions were only present in a minority of patients [2] and many patients presented with extranodal disease [1, 3, 4] Similar to our patient, no significant hypercalcemia or renal insufficiency was found, and only mild anemia [3, 4] Patients had both positive and negative EBV immunohistochemical staining [2-4]. Patients underwent a reduction in immunosuppression and treatment with proteasome inhibitor-based regimens with 20% also receiving autologous stem cell transplants. The median overall survival was 2.4 years and survival was decreased compared to regular multiple myeloma patients [1]. In conclusion, plasmacytoma/multiple myeloma type PTLD often presents without bone lesions, hypercalcemia, or renal insufficiency. Differentiation between this entity and other PTLD's with a prominent component of plasma cells (including marginal zone lymphoma) can be difficult, as both can produce monoclonal paraproteins. Treatment for plasmacytoma/multiple myeloma type PTLD is currently similar to conventional myeloma, however outcomes are inferior.

Epidemiological And Histopathologic Study Of Rhabdomyosarcoma cases in a tertiary Care hospital of Peshawar

&#x0D; Aim: This study aimed to find out rhabdomyosarcoma’s (RMS) histopathological and immunohistochemical features. Settings: The current study was carried out at the Department of Pathology, Section of Histopathology, Khyber Teaching Hospital Peshawar. The study duration was between from 1st January 2015 to 30th of December 2020. Results: In the current study, all the 300 occurrences were found to be relevant. The most prevalent rhabdomyosarcoma was embryonal rhabdomyosarcoma (ERMS) (87.4%), followed by alveolar rhabdomyosarcoma (ARMS) (9.4%). In the current study we found that embryonal rhabdomyosarcomas was most frequent in males (64%). ERMS were 16.1 percent found in the genitourinary system followed by neck and head region (46.7%). Most samples displayed positive Desmin and MyoD1 immunohistochemistry staining. Conclusions: It is consistent with previously published rhabdomyosarcoma data from all across the globe that our patients' epidemiologic information and microscopic findings are consistent with one other.&#x0D;

Neuroendocrine carcinoma admixed adenocarcinoma of cervix: A case report of young female

Neuroendocrine carcinoma coexisted with adenocarcinoma in cervix is very rare. This disease has a very poor prognosis and so far no standard treatment has been obtained. A 35-years-old woman seeks medical attention with chief complaint of bleeding per vagina outside of menstruation. Ultrasound shows cervical mass of 4.2 cm × 2.9 cm. Microscopic biopsy suggestive of a mixture of neuroendocrine cervical carcinoma and adenocarcinoma, moderate-poor differentiation. Several immunohistochemical staining of the biopsy tissue was done to detect neuroendocrine and adenocarcinoma. In biopsy tissue, P63 immunohistochemical staining was performed to detect squamous cell carcinoma with negative results. Furthermore chromogranin, synaptophycin, CD 56, NSE, and P40 immunohistochemical staining were performed to detect neuroendocrine with positive results and so did CK 19, CEA, and CK 7 staining to detect positive adenocarcinomas. This rare case had a positive immunohistochemical staining of both neuroendocrine carcinoma and adenocarcinoma cervix. Patient received definitive concurrent chemo-radiotherpay.

Evaluation of growth, viability, and structural integrity of equine endometrial organoids following cryopreservation

Reproductive diseases in mares are a significant cause of subfertility and profound economic loss in the equine industry. Utilizing a 3D in vitro cell culture system that recapitulates the in vivo physiology will reduce time, cost, and welfare concerns associated with in vivo reproductive research in mares. If this 3D model is combined with effective cryopreservation, reproductive research on mares can occur year-round, which is not currently possible in this seasonal species. Endometrial organoids, 3D in vitro cell clusters that exhibit in vivo uterine physiology, have been established in mice, women, and mares. Here we report the first comprehensive assessment of cryopreservation of endometrial organoids in the domestic mare. Organoid growth rate was not affected by the type of freezing media. However, growth rate varied among non-cryopreserved controls, organoids cryopreserved at passage 0 (P0), and organoids cryopreserved at passage 3 (P3). Additionally, there was no difference in organoid viability among freezing media or freezing timepoint (passages). Furthermore, fresh and frozen-thawed organoids displayed positive immunohistochemical staining for ZO-1, which is a marker for intercellular tight junctions, and for periodic acid-Schiff staining as marker for organoid function through mucin production. Results demonstrate that equine endometrial organoids can be cryopreserved with 10% dimethyl sulfoxide with minimal detrimental effects while maintaining intercellular tight junctions (ZO-1) and secretory function. Availability of cryopreserved endometrial organoids may permit expanded research on uterine pathologies that negatively affect mare fertility and improve efficiency, reduce cost, and minimize animal welfare concerns associated with in vivo research in the domestic mare.

Hepatic Adenomatosis in a Young Asymptomatic but High-risk Patient: An Incidental Diagnosis with Potentially Severe Clinical Implications.

Hepatic adenomatosis (HA) is a very rare condition and defined as the presence of 10 or more adenomas in an otherwise normal liver. HA has an incidence of 10–24% in patient with hepatic adenoma and it is more common in women. Most patients with HA are asymptomatic with a normal liver function test and half of cases are detected incidentally on imaging. Although HA is considered a benign disease, some patients may develop potentially fatal complications, such as hypovolaemic shock due to rupture of the liver lesion or malignant transformation to hepatocellular carcinoma.We report the case of a 29-year-old woman who presented to the emergency room after a car accident. Whole-body computed tomography revealed multiple focal hepatic hypervascular lesions in the right lobe of the liver together with a fatty liver. Subsequent hepatic magnetic resonance imaging suggested the diagnosis of HA with a suspicion of focal nodular hyperplasia (FNH). The patient refused to undergo liver biopsy, so we instituted a 3-month surveillance program, which included clinical assessment, liver function tests, tumour marker assessment and blood tests as well as sonographic evaluation for follow-up of the liver lesions.LEARNING POINTSHepatic adenomatosis is an extremely rare disease which predominantly affects women and is associated with hormone consumption, liver steatosis, glycogen storage disease, obesity, metabolic syndrome, abnormalities of hepatic vasculature and maturity onset diabetes of the young (MODY).The two main differential diagnoses include focal nodular hyperplasia (FNH) and well-differentiated hepatocellular carcinoma. Histological confirmation is required when MRI findings are inconclusive or when a malignancy is suspected.In men, resection of adenomas is mandatory due to the high risk of malignant transformation. In woman, a conservative approach with contraceptive discontinuation and biannual follow-up with MRI and alpha-fetoprotein is recommended; resection is needed in case of positive immunohistochemical staining for β-catenin on biopsy, symptomatic adenomas, adenoma increasing in size, and when malignancy cannot be ruled out.

A Rare Manifestation of a Presumed Non-Osteophilic Brain Neoplasm: Extensive Axial Skeletal Metastases From Glioblastoma With Primitive Neuronal Components.

BackgroundGlioblastoma multiforme (GBM) is the most common malignant tumor of the central nervous system. GBM with primitive neuronal component (GBM-PNC) is an aggressive variant identified in 0.5% of GBMs. Extracranial metastasis from GBM-PNC is a rare and challenging situation.MethodsA special case of early-onset GBM with systemic bone metastasis was enrolled. Clinical data, including patient characteristics, disease course, and serial radiological images were retrieved and analyzed. Tumor tissues were obtained by surgical resections and were made into formalin-fixed paraffin-embedded sections. Histopathological examinations and genetic testing were performed for both the primary and metastatic tumor specimens.ResultsA 20-year-old man suffered from GBM with acute intratumoral hemorrhage of the left temporal lobe. He was treated by gross total resection and chemoradiotherapy following the Stupp protocol. Seven months later, he returned with a five-week history of progressive neck pain and unsteady gait. The radiographic examinations identified vertebral collapse at C4 and C6. Similar osteolytic lesions were also observed at the thoracolumbar spine, pelvic, and left femur. Anterior spondylectomy of C4 and C6 was performed. The resected vertebral bodies were infiltrated with greyish, soft, and ill-defined tumor tissue. One month later, he developed mechanical low-back pain and paraplegia caused by thoracolumbar metastases. Another spine surgery was performed, including T10 total en-bloc spondylectomy, T7-9, L2-3, and L5-S1 laminectomy. After the operation, the patient’s neurological function and spinal stability remained stable. However, he finally succumbed to the rapidly increased tumor burden and died 15 months from onset because of cachexia and multiple organ failure. In addition to typical GBM morphology, the histological examinations identified monomorphic small-round cells with positive immunohistochemical staining of synaptophysin and CD99, indicating the coexistence of PNC. The next-generation sequencing detected pathogenic mutations in TP53 and DNMT3A. Based on above findings, a confirmed diagnosis of systemic metastases from GBM-PNC (IDH-wild type, WHO grade IV) was made.ConclusionsThe present case highlights the occurrence and severity of extensive axial skeletal metastases from GBM-PNC. This rare variant of GBM requires aggressive multimodal treatment including surgery and chemoradiotherapy targeting PNC. The pathological screening of PNC is recommended in patients with early-onset GBM and intratumoral hemorrhage. Surgery for spinal metastasis is appropriate in patients with chemoradioresistance and relatively good general status, with the objectives of restoring spinal stability and relieving spinal cord compression.

Cutaneous Amelanotic Signet-Ring Melanoma in a Siberian Tiger (Panthera tigris altaica)

A 15-year-old male white Siberian tiger (Panthera tigris altaica) was evaluated for an elevated, ulcerated, cutaneous mass on the right flank. The mass was removed by excisional biopsy and submitted for histopathology. Based on distinct histological features of intracytoplasmic globular material and positive immunohistochemical staining for Melan-A and vimentin, an amelanotic signet-ring melanoma was diagnosed. While in domestic cats this neoplasm is associated with malignancy and a short survival time, the tiger had no local recurrence or related clinical disease approximately 4 years post surgery. Cutaneous melanocytic tumours are rare in big cats, and the findings in this case suggest that amelanotic signet-ring melanoma is not as malignant as its counterpart in domestic cats.

Pulmonary tumor with Notochordal differentiation: a case report and morphologic, Immunohistochemical and molecular study of benign Notochordal cell tumor originating in the lung

BackgroundExtraosseous benign notochordal cell tumor is extremely rare, and there are only five reported cases worldwide. The presented case of pulmonary primary benign notochordal cell tumor is the sixth case, but the first to report the deletion mutation of EGFR gene exon 19.Case presentationThe patient was a 50-year-old asymptomatic woman, who had been followed up for 3 years for a nodule in the right lung. After ten months of the wedge resection, the patient is alive without evidence of recurrence or metastasis. The tumor was 7 mm in diameter and was well demarcated. The tumor was consisted of a sheet of large round vacuolated cells with small and bland nuclei. No connective tissue containing blood vessels or inflammatory cell infiltration was detected in the stroma. The tumor was positive for CK AE1/AE3, Vimentin, S100 and Brachyury. EGFR gene mutation and amplification were not detected.ConclusionsWe firstly reported the positive immunohistochemical staining for EGFR and the negative molecular results of EGFR gene of pulmonary primary benign notochordal cell tumor. Due to the rarity of this tumor, more reports are needed to explore pathological characteristics, especially the molecular characteristics, in order to better understand the nature of tumors.

NUT Midline Carcinoma Mimics Anaplastic Thyroid Carcinoma

Abstract Introduction/Objective NUT carcinoma (NC) is an extremely rare, aggressive subtype of squamous cell carcinoma defined by rearrangement of the NUTM1 (aka NUT) gene. NC most commonly arises within the thorax and head and neck and predominantly affects teens and young adults. For the first time, we described a rare case of NC mimics anaplastic thyroid carcinoma. Methods/Case Report A 27-year female with no significant past medical history presented with neck pain and swelling for a few months and was noted to have a “thyroid” mass. An ultrasound guided fine needle aspiration of the mass showed a hypercellular specimen composed of highly atypical epithelial cells with irregular nuclear membrane and prominent nucleolus, high nuclear to cytoplasmic ration, dense cytoplasm, lying singly or in flat sheet mixed with acute inflammatory exudate (Fig. A, B). No thyroid follicular cells or colloid are present. It was signed out as suspicious for squamous cell carcinoma since there was no cell block for further workup. A following excisional biopsy demonstrated similar atypical epithelium detached or embedded in skeletal muscle and soft tissue with acute, chronic inflammation and necrosis (Fig C). By immunohistochemical stains, the atypical cells are positive for p40 (Fig D) and p53. The Ki-67 proliferation index is ranging from 40 % to 70 %. Scattered tumor cells are weakly positive for PAX-8 and TTF-1. These findings raise the possibility that the squamous cell carcinoma might be a component of anaplastic thyroid carcinoma. However, molecular studies revealed a NSD3-NUTM1 fusion, which is characteristically identified in a subtype of squamous cell carcinoma know as NUT “midline” carcinoma. Results (if a Case Study enter NA) NA Conclusion Diagnosis of NC can be established by positive NUT nuclear immunohistochemical staining. Recognizing the typical morphology and keeping low threshold for the NUT immunohistochemical staining will increase the diagnostic efficacy.

S1917 Complicated Diverticulitis of the Sigmoid Flexure in a Patient with Left Nephrolithiasis

Introduction: Complicated diverticulitis is defined as diverticular inflammation associated with hemorrhage, abscess, phlegmon, perforation or obstruction. There are currently no reported cases of complicated diverticulitis occurring secondary to obstructive nephrolithiasis. We report a patient admitted for a left ureteral stone, whose significant perinephric inflammation was suspected to play a role in the development of complicated diverticulitis. Case description/methods: A 76 year old woman with history of recurrent nephrolithiasis presented with acute left flank pain. On arrival, she was mildly tachycardic. Physical exam was notable for left costovertebral angle tenderness. Labs were notable for an elevated blood urea nitrogen of 25 mg/dL. Computed tomography (CT) abdomen showed a 6 mm obstructing calculus within the left proximal ureter causing moderate hydronephrosis and significant peri-nephric inflammation. The patient was started on ceftriaxone. The next day, she had a worsening leukocytosis and an acute kidney injury, so she was taken urgently for left ureteral stent placement. Postoperatively, she had significant abdominal pain, so a repeat CT abdomen was obtained. It revealed inflamed diverticulum at the splenic flexure with an associated abscess abutting the spleen, consistent with complicated diverticulitis. She was managed supportively with nasogastric tube decompression, pain control, and broadened antibiotics. On hospital day 8, her abdominal pain worsened. Repeat CT abdomen showed enlargement of the perisplenic abscess and multiple new small abscesses anterior to the spleen. The patient was taken for laparoscopic splenectomy, which was complicated by iatrogenic perforation of the stomach, peritonitis, and septic shock. After a prolonged and complicated hospital stay in the surgical intensive care unit, the patient was discharged to a long term care facility. Discussion: Our patient's complicated diverticulitis was suspected to be secondary to her left ureteral stone. While most cases of diverticulitis occur at the sigmoid colon, our patient’s was at the splenic flexure, in close proximity to the left renal fossa where significant inflammation was noted on initial imaging. It is also possible that her diverticulitis was a consequence of iatrogenic ureteral injury during cystoscopy. Clinicians should be aware that complicated diverticulitis may occur in relation to nephrolithiasis.Figure 1.: a: Synaptophysin positive tumor cells b: Chromogranin A positive tumor cells c: Colonoscopy showing 2 cm mass at Hepatic flexure. d: High grade adenocarcinoma arising in a background of sessile serrated adenoma e: CK7 positive immunohistochemical staining.

Sporadic intra-abdominal desmoid tumor with a very unusual onset: two case reports

BackgroundIntra-abdominal desmoid tumors are rare soft tissue tumors that arise mainly in the mesentery and pelvis. Their etiology may include genetic mutations, estrogen-associated changes after childbirth, and mechanical factors such as a history of abdominal surgery. However, there are cases of intra-abdominal desmoid tumors that develop in the absence of such causes. Since they are rare, diagnosis is often difficult based on clinical findings. We encountered two cases of patients with sporadic intra-abdominal desmoid tumors with a very unusual onset and contrasting features.Case presentationThe first patient was a 51-year-old asian man who presented with sudden onset of abdominal pain. He was referred to our department because of a giant tumor detected on abdominal ultrasonography. Imaging revealed a 19-cm tumor with internal tumoral hemorrhage; however, no definitive diagnosis was made. Tumor resection was performed for diagnostic and therapeutic purposes. The second patient was a 41-year-old asian man, and right hydronephrosis was detected on abdominal ultrasonography during a periodic medical checkup. We diagnosed invasion of the primary mesenteric tumor into the right ureter using diagnostic imaging and performed ileocecal resection with partial right ureteral resection for a definitive diagnosis and therapeutic purposes. Although the tumors of both patients had developed from the ileal mesentery, the tumors were substantially different from each other based on their imaging findings, macroscopic morphology, and progression pattern. Meanwhile, they showed similar pathological characteristics. Both consisted of bundles of collagen fibrils of spindle-shaped fibroblasts with low cell atypia. Moreover, they were diagnosed as desmoid tumors using positive immunohistochemical staining for β-catenin.ConclusionsNeither patient had susceptibility factors for desmoid tumors, and to our knowledge, there have been very few reports to date of intra-abdominal desmoid tumors that were diagnosed because of acute abdominal pain caused by tumoral hemorrhage or asymptomatic obstructive uropathy. Furthermore, it is clinically interesting that the two patients showed contrasting progression patterns and imaging findings. Intra-abdominal desmoid tumors are rare and may present with various symptoms and findings similar to those observed in our patients. Diagnosis therefore requires experience and knowledge that is not bound by preconceptions.