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Raja R Seethala

Publications and source records attributed to Raja R Seethala.

11 recordsLinked to original sources
PubMed2026

Fibrotubular Tumors of the Thyroid: An Emerging Thyroid Neoplasm Characterized by Distinctive Morphology and Recurrent OCLN::PRKCI Gene Fusions Spanning the Adenoma-Carcinoma Spectrum.

The histopathologic and genomic landscape of thyroid tumors is well characterized, although new genetic alterations and tumor types are being described. We present 2 cases of thyroid tumors originating from follicular cells that had highly unusual and distinct morphologic features and carried an OCLN::PRKCI gene fusion. These tumors were well circumscribed, encapsulated, and composed of irregularly shaped tubular and follicular structures surrounded by layers of distinct fibrocollagenous basement membrane material positive for type IV collagen and laminin; they showed no definitive nuclear features of papillary carcinoma. Importantly, whereas one of the tumors had no invasive growth, the other demonstrated tumor capsule invasion, compatible with the adenoma-carcinoma spectrum seen in thyroid follicular and oncocytic tumors. Gene expression profiles of these tumors differed from those of common types of papillary thyroid carcinoma. The unusual and reproducible histopathologic characteristics and unique molecular profiles of these tumors support their designation as a distinct type of thyroid neoplasm that exists in noninvasive and invasive forms and, therefore, can be designated as fibrotubular adenoma and carcinoma. Recognition of this distinct entity is important for improving diagnostic accuracy and avoiding overtreatment of this likely indolent type of thyroid neoplasia.

Humans↗
PubMed2007

Epithelial-myoepithelial carcinoma: a review of the clinicopathologic spectrum and immunophenotypic characteristics in 61 tumors of the salivary glands and upper aerodigestive tract.

To further define the clinicopathologic spectrum of epithelial-myoepithelial carcinoma (EMCa), we report the gross, histologic, and immunophenotypic characteristics of 61 tumors seen within a 30-year-period. The mean age at presentation was 60.9 years, with a female predominance (1.5:1). The most common sites were parotid (62.1%), sinonasal mucoserous glands (10.3%), palate (8.6%), and submandibular (8.6%). Most EMCas showed a characteristic nodular/multinodular growth pattern and classic biphasic tubular histology. However, new morphologies in EMCa such as ancient change (8.2%), "Verocay"-like change (3.3%), and sebaceous differentiation (13.1%) were noted. Specific histologic variants were dedifferentiated EMCa (3.3%), oncocytic EMCa (8.2%), EMCa ex pleomorphic adenoma (1.6%), double-clear EMCa (3.3%), and EMCa with myoepithelial anaplasia (3.3%). All cytokeratin cocktails selectively highlighted the epithelial component well. Of the myoepithelial markers, p63, smooth muscle actin and vimentin performed best. Bcl-2 and c-kit were frequently positive (66.7% and 69.2%, respectively). p53 was highly expressed only in 1 dedifferentiated EMCa. The recurrence rate was 36.3% (median disease-free survival 11.34 y), but death was rare with 5-year and 10-year disease-specific survivals of 93.5% and 81.8%, respectively. The most important univariate predictors of recurrence were margin status (log rank P=0.006), angiolymphatic invasion (P=0.002), tumor necrosis (P=0.004), and myoepithelial anaplasia (P=0.038). Thus, EMCa is generally a low-grade tumor with a broader morphologic spectrum than previously thought, with several key features predictive of recurrence. Immunohistochemistry can aid diagnosis by highlighting the biphasic nature of the tumor.

Adolescent↗
PubMed2006

Posttreatment assessment of response using FDG-PET/CT for patients treated with definitive radiation therapy for head and neck cancers.

PURPOSE: The goal of this study was to evaluate coregistered [18F] fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) for the detection of persistent disease after definitive radiation therapy in head and neck cancer. METHODS AND MATERIALS: Posttreatment FDG-PET/CT was performed in 28 patients on average 8 weeks (range, 4 to 15.7 weeks) after completing definitive radiation therapy. FDG-PET/CT was visually analyzed for the entire patient group and at two time points (4-8 and >8 weeks) after treatment. The contrast-enhanced CT portion of PET/CT was separately analyzed blinded to the results of coregistered FDG-PET/CT and classified as negative or positive for residual locoregional disease. Pathologic findings and clinical follow-up served as the reference standard. RESULTS: Follow-up data were available for all 28 patients (median, 17.6 months). Regarding the detection of residual disease, the overall sensitivity and specificity of FDG-PET/CT was 76.9% and 93.3%, respectively, compared with 92.3% and 46.7% for contrast-enhanced CT. The accuracy of FDG-PET/CT was 85.7%, compared with 67.9% for CT alone. All false-negative (n = 3) and false-positive (n = 1) FDG-PET/CT results occurred between 4 and 8 weeks after treatment. At 8 weeks or later after treatment, the specificity of CT was 28%, compared with 100% for FDG-PET/CT. CONCLUSIONS: The metabolic-anatomic information from coregistered FDG-PET/CT provided the most accurate assessment for treatment response when performed later than 8 weeks after the conclusion of radiation therapy. FDG-PET/CT excelled by a higher specificity and overall diagnostic performance than CT imaging alone. These results support a potential clinical role of FDG-PET/CT in the early assessment of therapy response after definitive radiation therapy.

Adult↗
PubMed2006

Primary angiosarcoma of the bladder.

CONTEXT: Primary bladder angiosarcomas are extremely rare, and their clinical and pathologic features are not well described. OBJECTIVE: To further refine the clinical features of primary bladder angiosarcomas and define their pathologic spectra. DATA SOURCES: Relevant sources were identified using MEDLINE and a subsequent bibliographic search of all pertinent reports and reviews. We also searched the M. D. Anderson pathology archives. STUDY SELECTION: After excluding 4 cases that likely secondarily involved the bladder, we identified 9 true primary bladder angiosarcomas. DATA EXTRACTION: Data were extracted on the following: demographics, clinical presentation, predisposing factors, gross pathology, microscopic pathology, immunophenotype, therapy, and outcomes. DATA SYNTHESIS: Primary bladder angiosarcomas were found at a mean age of 64.2 years, with a male-female ratio of 8:1. Two cases arose in a postirradiation setting. Primary bladder angiosarcomas typically presented with hematuria and were grossly hemorrhagic, raised masses (mean size, 6.7 cm) of the trigone and/or dome. Histologically, most showed classic anastomosing channels lined by plump hyperchromatic cells, though many showed variant histology such as solid growth and epithelioid cytology. Three (43%) of 7 patients died within a year, but only 1 patient died with evidence of disease. The remaining patients were alive at the time of publication of their respective cases (mean, 22 months). CONCLUSIONS: Primary angiosarcomas of the bladder are typically rare tumors of middle-aged and elderly men that present with locally advanced disease and show a wide histologic spectrum. However, their prognosis may be better than previously thought.

Age Distribution↗
PubMed2006

Postirradiation osteosarcoma of the mandible with heterologous differentiation.

Heterologous differentiation in osteosarcoma is rare, with only 17 cases previously described in the literature. We report a case of a mandibular osteoblastic osteosarcoma with rhabdomyosarcomatous differentiation in a 45-year-old man who had a history of Hodgkin lymphoma that was treated with chemotherapy and radiation. Radiographs showed a destructive osteoblastic tumor of the mandible that was proven by biopsy to be osteosarcoma. After the patient underwent neoadjuvant chemotherapy, the tumor was resected. It contained a high-grade osteosarcoma composed of osteoblastic and chondroblastic elements that had no definitive response to therapy. Within the center of the lesion was a discrete focus of pleomorphic cells with rhabdomyosarcomatous differentiation that was confirmed by immunohistochemical stains for desmin, myogenin, and myogenic differentiation antigen 1. The patient received additional chemotherapy and radiation therapy but developed lung, brain, and spinal metastases and died 7 months after surgery. To our knowledge, this is the first report of osteosarcoma of the mandible with heterologous differentiation.

Cell Transformation, Neoplastic↗
PubMed2005

Relative accuracy of fine-needle aspiration and frozen section in the diagnosis of lesions of the parotid gland.

BACKGROUND: Both fine-needle aspiration (FNA) and frozen section (FS), although useful in preoperative and intraoperative management, have their advantages and pitfalls when used in the diagnosis of salivary gland lesions. The accuracy of each of these modalities has been assessed separately in many studies; a direct comparison of these techniques on a large cohort has not been well studied. Herein, we determine the relative accuracies of both FNA and FS in the diagnosis of salivary gland lesions. METHODS: We reviewed a cohort of 220 cases of parotid gland FNA with histologic follow-up; FS was performed in 57 cases (26%). The sensitivity, specificity, and accuracy of FNA and FS were determined with respect to the final histologic diagnosis. For these calculations, benign diagnosis was considered negative, whereas a malignant diagnosis was considered positive. In addition, we re-reviewed the FNA and FS slides in cases that had conflicting FNA and FS results. RESULTS: Of the 220 cases examined, the FNA diagnoses were as follows: benign (n = 142), malignant (n = 52), indeterminate (n = 14), and nondiagnostic (n = 12). Correlating these findings with the histologic findings, nine cases (4%) were false negative, whereas 12 (5%) were false positive. The sensitivity, specificity, and accuracy for FNA when diagnostic were 86%, 92%, and 90%, respectively. In 57 cases with FS, seven (12%) were false negative, whereas none were false positive. The FS was able to change to benign four diagnoses that were malignant by FNA and provide a diagnosis for five nondiagnostic FNAs. The sensitivity, specificity, and accuracy for FS were 77%, 100%, and 88%, respectively. The sensitivity, specificity, and accuracy for FNA and FS combined were 90%, 100%, and 95%, respectively. CONCLUSIONS: Both FNA and FS provide a similar accuracy. FS may be useful if FNA is nondiagnostic and may also be useful in confirming or refuting malignancy in some cases. Hence, both techniques are complementary to each other in the diagnosis of salivary gland lesions.

Adenolymphoma↗
PubMed2005

Comparison of p63 and p73 expression in benign and malignant salivary gland lesions.

BACKGROUND: The p63 and p73 genes are members of the p53 family and play an important role in stem cell identity and cellular differentiation and are expressed in basal and myoepithelial cells. In this study, we examined the expression of p63 and p73 in 50 various benign salivary gland lesions and 45 malignant salivary gland tumors. METHODS: The 95 salivary gland tumors were selected from the archives of the Department of Pathology and Laboratory Medicine at the Hospital of the University of Pennsylvania. Sectioned formalin-fixed paraffin-embedded tissue cut at 3 mum was immunostained with antibodies that recognize all isozymes of p63 and p73 and evaluated with respect to percentage of positive cells and localization. RESULTS: In benign lesions, p63 and p73 nuclear reactivity was seen in 46 (92%) of 50 and 47 (94%) of 50 cases, respectively. In malignant tumors, p63 and p73 were seen in 34 (76%) of 45 and 40 (89%) of 45 cases, respectively. A significant difference between p63 and p73 positivity was only seen in adenoid cystic carcinomas (p = .006). Also, p73 was found in tumors with minimal basal/myoepithelial differentiation. CONCLUSIONS: Hence, p63 and p73 expression is retained in both benign and malignant salivary gland tumors with basaloid or myoepithelial differentiation. Hence, p63 seems to be a more specific marker of myoepithelial differentiation than p73.

Biomarkers, Tumor↗
PubMed2004

Immunohistochemical evaluation of microphthalmia-associated transcription factor expression in giant cell lesions.

Microphthalmia-associated transcription factor (Mitf), a member of the helix-loop-helix transcription factor subfamily, normally expressed in mononuclear and multinucleated osteoclasts, is involved in the terminal differentiation of osteoclasts. Dysfunction of osteoclast activity resulting from abnormal Mitf expression has been implicated in osteopetrosis. Numerous other giant cells of various types including osteoclast-like giant cells seen in various tumors, traditionally thought to be monocyte derived, are seen in a variety of bone and extraosseous lesions. Using a monoclonal antibody with a standard immunohistochemical technique on paraffin sections, we evaluated expression of Mitf in 89 various giant cell lesions including giant cell tumor of bone (n26), giant cell tumor of tendon sheath/pigmented villonodular synovitis (n24), giant cell reparative granuloma (n3), aneurysmal bone cysts (n11), chondroblastomas (n7), foreign body giant cell reaction (n10), and sarcoidosis (n8). We also evaluated three cases of osteopetrosis and 27 various tissues without monocyte-derived giant cells (nine bone marrows, nine products of conception, seven lymph nodes with sinus histiocytosis, one granulation tissue and one thymus). Nuclear Mitf immunoreactivity was evaluated. Mitf was variably expressed in the monocyte-derived giant cells and/or the adjacent mononuclear cells/histiocytes in 23 (89%) giant cell tumors of the bone, 23 (96%) giant cell tumors of tendon sheath/pigmented villonodular synovitis, three (100%) giant cell reparative granuloma, eight (73%) aneurysmal bone cysts, five (71%) chondroblastomas, eight (80%) foreign-body giant cell reactions, and six (75%) sarcoidoses. No Mitf immunoreactivity was detected in cases of osteopetrosis and giant cells of nonmonocyte origin. Mitf immunoreactivity is rare in tissues with rich mononuclear cells/histiocytes but no monocyte derived giant cells. These findings support the notion that giant cells in giant cell lesions are likely derived from adjacent mononuclear cells and Mitf might play a role in the multinucleation process of such cells.

Cell Nucleus↗
PubMed2003

Diffuse fibrous pseudotumor of the testicular tunics associated with an inflamed hydrocele.

Fibrous pseudotumors of the testicular tunics and paratesticular soft tissue are uncommon lesions. They typically arise as painless scrotal masses that may be associated with a hydrocele or history of trauma or infection. Although these lesions are clinically worrisome for a malignant neoplasm, they are thought to be reactive in nature, since they are composed of dense fibrous tissue with interspersed bland fibroblasts and myofibroblasts and mixed inflammatory cells. Once excised, these lesions behave in a benign fashion. Typically, these masses are multinodular, but in rare cases they are diffuse, bandlike myofibroblastic proliferations that encase the testis and are termed fibromatous periorchitis. Herein, we describe a 57-year-old man with a diffuse fibrous pseudotumor/fibromatous periorchitis that encased the left testis and adnexa and arose in close apposition to an inflamed hydrocele.

Fibroma↗