Uracil as a biomarker for spatial pyrimidine metabolism in the development of gingivobuccal oral squamous cell carcinoma.

No biomarker has yet been identified that allows accurate diagnosis and prognosis of oral cancers. In this study, we investigated the presence of key metabolites in oral cancer using proton nuclear magnetic resonance (NMR) spectroscopy to identify metabolic biomarkers of gingivobuccal oral squamous cell carcinoma (GB-OSCC). NMR spectroscopy revealed that uracil was expressed in 83.09% of tumor tissues and pyrimidine metabolism was active in GB-OSCC; these results correlated well with immunohistochemistry (IHC) and RNA sequencing data. Based on further gene and protein analyses, we proposed a pathway for the production of uracil in GB-OSCC tissues. Uridinetriphosphate (UTP) is hydrolyzed to uridine diphosphate (UDP) by CD39 in the tumor microenvironment (TME). We hypothesized that UDP enters the cell with the help of the UDP-specific P2Y6 receptor for further processing by ENTPD4/5 to produce uracil. As the ATP reserves diminish, the weakened immune cells in the TME utilize pyrimidine metabolism as fuel for antitumor activity, and the same mechanism is hijacked by the tumor cells to promote their survival. Correspondingly, the differential expression of ENTPD4 and ENTPD5 in immune and tumor cells, respectively, indicatedtheir involvement in disease progression. Furthermore, higher uracil levels were detected in patients with lymph node metastasis, indicating that metastatic potential is increased in the presence of uracil. The presence of uracil and/or expression patterns of intermediate molecules in purine and pyrimidine pathways, such asCD39, CD73, and P2Y6 receptors together with ENTPD4 and ENTPD5, hold promise as biomarker(s) for oral cancer diagnosis and prognosis.

Adamantinoma with a Prominent Spindle Cell Component Mimicking Intraosseous Synovial Sarcoma: Clinicopathological Features of Six Tumors.

Introduction. Adamantinoma is sub-classified into classic/biphasic, osteofibrous dysplasia-like, and de-differentiated type. We present six adamantinomas with a prominent spindle cell component mimicking intraosseous synovial sarcomas. Methods. Six patients were either referred with a diagnosis of intraosseous synovial sarcoma or wherein synovial sarcoma was a differential diagnosis. Three tumors were tested for SS18 gene rearrangement by FISH and two for SS18::SSX fusion by RT-PCR technique. Results. There were three males and three females with an average age of 20.6 years. Radiologically, the lesions were expansile and showed lytic and/or sclerotic components, involving the cortex and/or medulla. Five lesions occurred in the tibia and two in the fibula. Two tumors displayed soft tissue extension and two occurred as multifocal lesions. Two patients were diagnosed with synovial sarcoma and a single patient with sarcomatoid carcinoma, elsewhere. Two "in-house" patients were initially diagnosed with synovial sarcomas. On review, all tumors were cellular comprising monomorphic spindle-shaped cells arranged in sheets and fascicles (n = 6), including a "herringbone-like" pattern (n = 3), focal tubules (n = 1), cohesive nests (n = 5), cords (n = 2), including pseudocystic component (n = 2). Immunohistochemically, tumor cells were positive for p63 (6/6), p40 (4/4), EMA (2/3), AE1/AE3 (5/6), various keratins (2/2), and TLE1 (2/4). Three tumors tested for SS18 rearrangement were negative, while two tumors tested for SS18::SSX fusion were negative. Conclusions. Adamantinomas with spindle cell morphology display overlapping features with synovial sarcoma. A clinico-radiological index of suspicion immunostains (p63 and p40) and molecular test for t(X; 18) translocation are useful in an exact diagnosis, which has treatment-related implications.

Study of histopathology reports of loop electrosurgical excision procedure of cervical transformation zone and their correlation with preprocedural cervical biopsy and/or cytology: An audit.

Introduction: Loop electrosurgical procedure of the transformation zone of the cervix (LEEP) is the preferred method for many investigators for early detection and treatment of high grade intraepithelial neoplasia(HGCIN). Histopathology reports of LEEP should contain information about the diagnosis, presence or absence of neoplasia ( with its grade) and comment on excison margins. Aim: Our aim was to study LEEP reports for its contents and to see their correlation with preprocudure histology and/or cytology report. Results: Between 2011 and 2017, 44 LEEP reports were archived and studied for their contents from our records. Slides were not reviewed. Mean age was 47.66 years (median 47 years). Forty two (( 95.45%) reports mentioned that all the tissue was examined. Deep cut examination was mentioned in 17/44 cases (38.64%). The concordance rate between LEEP and preprocudure histology and /or cytology for CIN II plus diagnosis is 65.9%. A strict definition is used. If, however, diagnoses between inflammation and CIN I, ASC-H and inflammation, and ASC-H and CIN I are considered non discordant, then the concordance rate rises to 72.7 %. The breakup of discordant cases is given. Conclusion: Literature shows wide range of concordance due to variable definitions and variety of reasons; possible reasons are discussed.

Secretory carcinoma of the breast, commonly exhibits the features of low grade, triple negative breast carcinoma- A Case report with updated review of literature.

Secretory carcinoma of the breast (SBC) is a rare breast neoplasm. Most of the patients present at an early stage with a relatively indolent clinical course. Lymph node and distant metastasis are also very infrequent. The histomorphological features of the secretory breast carcinoma are quite characteristic. Predominantly three histological patterns, solid, microcystic, and tubular, have been noted with copious amounts of intra and extracellular secretory material. Most commonly, no positivity for estrogen receptor (ER), progesterone receptor (PR) and ERBB2(HER2/neu) is observed in SBCs. As SBC can occasionally be hormone receptor-positive, they should not be categorized in the triple-negative breast carcinoma (TNBC) group in general. A very characteristic genetic translocation t (12;15) has been noted in this rare tumor, resulting in a fusion between ETV6 and NTRK3 proteins. We present a case of a 60-year-old lady who presented with right breast lump of 1-month duration and was managed by lumpectomy and sentinel lymph node dissection. Axillary dissection was not performed because the sentinel lymph node biopsy was negative. Postoperative radiotherapy was given to the right breast with a boost to the tumor bed. No adjuvant chemotherapy was given No recurrence has been noted even after a year of the completion of treatment.

Grossing and reporting of a soft tissue tumor specimen in surgical pathology: Rationale, current evidence, and recommendations.

Soft tissue tumors, including sarcomas are complex and diagnostically challenging tumors. This is as a result of their heterogeneity and overlapping clinicopathological, immunohistochemical and also molecular features, the latter to some extent. More than 80 types of sarcoma have been described. Current management, which is best offered at centers with active multidisciplinary care, is based on balancing oncologic and functional outcomes in such cases. This has transcended into the types of specimens received for grossing these rather uncommon tumors. Over the years, diagnostic specimens have reduced in their sizes from, open biopsies to core needle biopsies. These specimens need to be adequately and judiciously triaged for ancillary techniques, such as molecular testing. Conservative surgeries have led to resected specimens for marginal assessment. Lately, post neoadjuvant (chemotherapy or radiation therapy)-treated resection specimens of soft tissue sarcomas are being submitted for surgical pathology reporting. This article focuses on the grossing of soft tissue tumors, including sarcomas, in terms of types of specimens, grossing techniques including rationale, tissue triage, reporting, and recommendations from the surgical pathologists actively engaged in reporting musculoskeletal tumors, based on current evidence.

Secretory carcinoma of the breast, commonly exhibits the features of low grade, triple negative breast carcinoma- A Case report with updated review of literature

Secretory carcinoma of the breast (SBC) is a rare breast neoplasm. Most of the patients present at an early stage with a relatively indolent clinical course. Lymph node and distant metastasis are also very infrequent. The histomorphological features of the secretory breast carcinoma are quite characteristic. Predominantly three histological patterns, solid, microcystic, and tubular, have been noted with copious amounts of intra and extracellular secretory material. Most commonly, no positivity for estrogen receptor (ER), progesterone receptor (PR) and ERBB2(HER2/neu) is observed in SBCs. As SBC can occasionally be hormone receptor-positive, they should not be categorized in the triple-negative breast carcinoma (TNBC) group in general. A very characteristic genetic translocation t (12;15) has been noted in this rare tumor, resulting in a fusion between ETV6 and NTRK3 proteins. We present a case of a 60-year-old lady who presented with right breast lump of 1-month duration and was managed by lumpectomy and sentinel lymph node dissection. Axillary dissection was not performed because the sentinel lymph node biopsy was negative. Postoperative radiotherapy was given to the right breast with a boost to the tumor bed. No adjuvant chemotherapy was given No recurrence has been noted even after a year of the completion of treatment

Superficial CD34-positive fibroblastic tumor in the forearm of a middle-aged patient: A newly described, rare soft-tissue tumor.

Superficial CD34-positive fibroblastic tumor is a recently described soft-tissue tumor entity. A 48 year-old-male presented with a gradually increasing soft-tissue mass in his right forearm of 2 years' duration, along with multiple subcutaneous soft-tissue nodular lesions, and reminiscent of lipomas over his body. He underwent a wide excision of his forearm mass. Microscopic sections showed a circumscribed tumor in the dermis and subcutaneous fat, composed of spindle cells, inflammatory cells, including lymphocytes, plasma cells, and eosinophils, along with interspersed markedly pleomorphic giant cells containing moderate-to-abundant "glassy" cytoplasm, vesicular nuclei, exhibiting prominent nucleoli, and intranuclear pseudoinclusions. There were no significant mitotic figures, areas of hemorrhage, necrosis, or pigment histiocytes. By immunohistochemistry, the tumor cells were diffusely positive for CD34 while negative for cytokeratin (CK), pan CK (AE1/AE3), S100 protein, CD30, and CD31. MIB1/Ki-67 was low and highlighted 4%-5% tumor nuclei. Diagnosis of superficial CD34-positive fibroblastic tumor was offered. Sections from the various resection margins were free of tumor. Postresection, the patient is alive with no evidence of disease for the past 8 months. This constitutes as one of the first case reports of this rare tumor entity from our country. Its diagnostic and treatment implications are discussed herewith.

Clinicopathologic features of four rare types of chordomas, confirmed by brachyury immunostaining.

BACKGROUND: A wide clinicopathologic spectrum of a chordoma exists. Brachyury constitutes as its most useful diagnostic immunohistochemical (IHC) marker. METHODS: During a 7-year-period, 4 unusual histopathologic types of chordomas were identified. Immunohistochemistry was performed by polymer technique. RESULTS: Clinicopathologic features of the 4 cases are as follows: Cases 1 and 2: Two tumors occurred in the sacrococcygeal and lumbosacral regions of a 42-year-old male and a 34-year-old female, respectively. Histopathologic examination showed areas of classical chordoma; juxtaposed to a high-grade, spindle cell sarcoma. By IHC, cytokeratin (CK), epithelial membrane antigen (EMA), S-100 protein, and brachyury were found to be distinctly positive in the differentiated chordomatous areas. Both these cases were diagnosed as dedifferentiated chordomas. The first patient, postresection and adjuvant radiation therapy (RT), died after 14 months of therapy. Case 3: A 58-year-old male presented with pain in his sacral region and urinary incontinence. Imaging disclosed a sacral mass. Histopathologic examination showed physaliphorous cells intimately admixed with, markedly pleomorphic cells, scattered mitotic figures, and focal tumor necrosis. By IHC, the tumor cells were positive for CK, AE1/AE3, S-100 protein, brachyury, and INI1/SMARCB1. The diagnosis of a poorly differentiated chordoma was offered. Despite surgical resection and adjuvant RT, the patient died within 18 months. Case 4: A 58-year-old male presented with a soft tissue lesion in his left leg. Histopathologic examination showed physaliphorous cells, embedded in a myxohyaline stroma. By IHC, the tumor cells were positive for EMA, S-100 protein, brachyury, and INI1. Diagnosis of an extra-axial, soft tissue chordoma was offered. CONCLUSIONS: These four unusual chordomas, confirmed by brachyury immunoexpression, constitute as one of the first such documentation from our country, revealing a wide clinicopathologic spectrum of chordomas. Dedifferentiated and poorly differentiated chordomas are associated with an aggressive clinical course. Further diagnostic implications are discussed herewith.

T-cell Lymphoma of Thyroid Gland with Lennert Type of Morphology: A Case Report and Review of the Literature.

The rare entity of primary T-cell lymphoma of thyroid gland may pose great diagnostic and therapeutic challenges to the pathologist and clinician. There are very few case and short series reports of these tumors describing their varied clinicopathologic features in English literature. We report a case of mature T-cell lymphoma of thyroid in a 26 year old male, with unique pseudogranulomatous and lymphohistiocytic Lennert type of morphology, on a background of autoimmune thyroiditis. This man, diagnosed with Hashimoto's thyroiditis for the previous 2 years, underwent thyroidectomy for sudden onset of pressure symptoms. The diagnosis of T-cell lymphoma was made on the thyroid tissue based on histopathologic and immunophenotypic findings, in concert with the results of T-cell receptor gene rearrangement studies by polymerase chain reaction. Later, after about 3 months, similar findings were confirmed in an excision biopsy from a left cervical lymph node in the patient. The patient has been started on chemotherapy with gemcitabine, dexamethasone, and cisplatin along with involved field radiotherapy; however, he has shown a rapid upstaging of disease from stage IE to IIIE in a short period of 3 months with relatively well preserved clinical parameters until the latest follow up.