Nonossifying Fibroma Involving Epiphysis of Long Bone-Case Report and Review of the Literature.

Nonossifying fibroma (NOF) is a common benign bone neoplasm and is usually observed in the first 2 decades of life. Most NOFs occur in the metaphysis of long bones of the lower extremities and migrate toward the diaphysis during skeletal maturation. Epiphyseal involvement by NOF has been rarely reported, with only one case found in the English literature. The authors report the second case of NOF involving the epiphysis of a long bone, the proximal tibia of a 21-year-old woman. Clinicians and pathologists should be aware of the rare possibility of epiphyseal involvement of long bones by this condition. Pathologists should select appropriate immunohistochemistry markers to rule out alternative diagnoses.

Extramedullary Hematopoiesis Adjacent to Vertebral Fracture in a Patient with Pernicious Anemia: Support for a Mechanical Extrusion Mechanism.

CASE: A 68-year-old woman presented with a paraspinal mass of indeterminate imaging characteristics. Workup and computed tomography-guided Fine Needle Aspiration (FNA) aspiration revealed extramedullary hematopoiesis (EMH) adjacent to a prior compression fracture in the setting of pernicious anemia. CONCLUSION: The combination of findings suggests a possible relationship of the compression fracture and the EMH because of traumatic extravasation of marrow contents, with the patient's underlying anemia possibly providing an underlying predisposition to EMH.

Low-grade Fibromyxoid Sarcoma With Heterotopic Bone Formation: Case Report and Review of the Literature.

Low-grade fibromyxoid sarcoma is an uncommon soft tissue malignant neoplasm with deceptively bland histologic appearance, and a tendency for late recurrence and metastasis. Cases with significant heterotopic ossification are exceedingly rare. In the literature, only 9 cases of low-grade fibromyxoid sarcoma with bone formation proven by histopathology have been described in detail in the literature. We report the case of a 42-year-old male presenting with a 20-year history of a painless tumor in his left upper thigh. Computed tomography images showed coarse punctate central and peripheral calcifications, and the mass was resected. The tumor cells were immunohistochemically positive for MUC4, and also positive for FUS (16p11.2) gene rearrangement by fluorescence in situ hybridization. Besides, immunohistochemistry showed focal weak to moderate staining for TLE-1. At histology, heterotopic ossification was also observed. A diagnosis of low-grade fibromyxoid sarcoma (grade 1, stage T4) was rendered, and prior reports of these tumors with bone formation have not concomitantly described TLE-1 staining. This paper aims to characterize the radiologic, pathologic, and clinical features of low-grade fibromyxoid sarcoma showing heterotopic ossification reported in the literature, and further review the morphologic spectrum of this malignant neoplasm.

A Case of TFE3-positive Non-neoplastic Pseudodecidualized Endometrium Presenting as a Cervical Mass.

Transcription factor E3 (TFE3) represents a useful target for immunohistochemistry assays in routine surgical pathology practice. This protein has shown nuclear expression in a variety of normal tissues; however, this expression is usually at very low levels, while strong nuclear immunoreactivity of TFE3 has been seen almost exclusively in tumors. We present the case of a 30-year-old female on oral contraceptive pill (drospirenone/ethinylestradiol) and with complaints of dysmenorrhea and menorrhagia. She was found to have a cervical mass on pelvic ultrasound, and the biopsy showed fragments of benign squamous epithelium and polypoid endometrial tissue with stromal pseudodecidualization and abundant mixed inflammation. The pseudodecidualized stromal component showed moderate to strong nuclear staining in ~85% of stromal cells for TFE3. We discuss the intracellular role of TFE3 during inflammatory states and hypothesize that TFE3 expression can be associated with ongoing inflammation. Our case shed light upon the possibility that non-neoplastic environments with an inflammatory background could lead to increased nuclear expression of TFE3. Pathologists should be aware of the possibility of strong nuclear expression of TFE3 in non-neoplastic endometrium to avoid potential misdiagnosis.

Primary Neuroendocrine Tumor of the Scrotum: An Uncommon Site for a Rare Tumor.

Neuroendocrine tumors (NETs) are a heterogeneous group of tumors developing from neural crest cells, with numerous sites of origin, commonly the gastrointestinal and genitourinary tracts. NETs of the genitourinary tract are more common in women. Small cell carcinoma of the prostate or testicular carcinoid are the NETs in male. In this article, we present a rare case of NET of the scrotum. Our patient was a 47-year-old male with a history of complicated pilonidal cysts resulting in chronic scrotal wounds. Biopsy of a large nonhealing scrotal wound revealed a high-grade neuroendocrine carcinoma with features most suggestive of small cell carcinoma. Presenting with advanced disease at diagnosis, he was started on systemic therapy and unfortunately progressed through multiple lines of treatment, including CAPTEM (capecitabine and temozolomide). Unfortunately, due to multiple logistical reasons, the patient was unable to receive the then off-label immunotherapy based on DART (Dual Anti-CTLA-4 and Anti-PD-1 Blockade in Rare Tumors) trial. He, unfortunately, succumbed to his disease within months of diagnosis.

Anaplastic Transformation in Myxopapillary Ependymoma: A Report of 2 Cases and Review of the Literature.

Myxopapillary ependymoma (MPE) is a relatively common neoplasm arising primarily in the filum terminale/lumbosacral region of the spinal cord. It is designated as a grade I tumor in the most recent WHO Classification of Tumours of the CNS, although aggressive clinical behavior can be observed, especially in cases arising in an extradural location. Anaplastic transformation in MPE is exceedingly rare with <20 examples reported in the English literature, and consensus on diagnostic features and definitive grading remain to be determined. Here, we present 2 cases of recurrent MPE with anaplastic features, both of which had histology consistent with conventional MPE as well as areas with significant atypia, frequent mitotic figures, elevated Ki-67 proliferation indices (>10%-50%), necrosis, and focal vascular proliferation. Targeted next-generation sequencing panels revealed no definitive pathogenic mutations or fusion proteins in either case. Copy number profiling, methylation profiling, and t-Distributed Stochastic Neighbor Embedding were performed to investigate the molecular characteristics of these tumors. To the best of our knowledge, these are the first reported cases of MPE with anaplastic features with methylation profiling data. In addition, we review the literature and discuss common histologic and molecular findings associated with anaplastic features in MPE.

Cytokeratin-Positive Osteosarcoma Simulating Sarcomatoid Metastatic Carcinoma.

Osteosarcoma, the most common primary malignant bone tumor, rarely stains positive for epithelial markers such as cytokeratin on immunohistochemical analysis. We describe a 52-year-old man with a destructive distal femoral metaphyseal lesion who was initially treated for metastatic sarcomatoid carcinoma based on extensive radiographic and histopathologic evaluation. Ultimately, wide resection of the distal femur was performed, revealing high-grade conventional osteosarcoma with intense and diffuse cytokeratin positivity. Such immunohistochemical staining in osteosarcoma is rare, making it difficult to distinguish cytokeratin-positive osteosarcoma from metastatic carcinoma. The presence of a cytokeratin-positive bone neoplasm with malignant osteoid formation on histological studies as well as integration with clinical and radiologic data can help confirm osteosarcoma as the ultimate diagnosis.

TLE-1-Positive Angiomatoid Fibrous Histiocytoma Mimicking Synovial Sarcoma.

Angiomatoid fibrous histiocytoma (AFH) is a rare soft tissue tumor most commonly seen in young adults and children. We report a case with morphology and immunohistochemistry supporting the diagnosis of synovial sarcoma. On core biopsy, the tumor had spindle cell and epithelioid morphology with a myxoid background. Staining for transducin-like enhancer of split 1 and CD99 were positive; however, subsequent fluorescence in situ hybridization for SYT (SS18, nBAF chromatin remodeling complex subunit) break apart returned negative. Further study showed fluorescence in situ hybridization for EWSR1 (EWS RNA binding protein 1) gene rearrangement, supporting the diagnosis of AFH. The resected specimen showed a predominant spindle cell proliferation along with histiocytoid areas supporting a diagnosis of AFH. This case report highlights the fact that synovial sarcoma and AFH can overlap morphologically and immunohistochemically. When approaching a biopsy specimen with spindle cell morphology, and transducin-like enhancer of split 1, CD99, and epithelial membrane antigen positivity it is important to include AFH in the differential diagnosis.

Association of MnSOD AA Genotype with the Progression of Prostate Cancer.

PURPOSE: To investigate whether manganese superoxide dismutase (MnSOD) genetic polymorphism is associated with the clinical significance of prostate cancer. MATERIALS AND METHODS: Prostates were obtained from 194 deceased men 45 years or older who did not have a history of prostate cancer. Serial sections and histological examinations of the prostate were performed. The MnSOD genotypes of the specimens were determined by polymerase chain reaction restriction fragment length polymorphism analysis. RESULTS: Of the 194 men, 31 and 26 had clinically insignificant and significant prostate cancer. Clinically significant cancer comprised 29% and 58% of the cancers in men <70 and >70 years old, respectively. The age-specific proportion of significant cancer significantly increased with the advance of age (p<0.001). MnSOD AA, as compared with the other genotypes (VA and VV together), was associated with significant prostate cancer across all ages, odds ratio (OR) 2.34, 95% confidence interval (CI) 0.99-5.49, and in men older than 69 years (OR 4.89, 95% CI 1.51-15.8), but not in men younger than 70 years. The genotype was not associated with clinically insignificant cancer regardless of age. The comparison between significant and insignificant cancer, the OR (95% CI) for MnSOD AA was 5.04 (1.05-24.2) (sensitivity 0.57, specificity 0.78, positive predictive value 0.78) in men older than 69 years. CONCLUSIONS: MnSOD polymorphism is strongly associated with the clinical significance of prostate cancer in men older than 69 years, but not in men younger than 70 years suggesting that oxidative stress may be involved in the progression of the disease. MnSOD may be a clinically useful marker to predict the potential of progression of prostate cancer.

Radiation-induced epithelial-myoepithelial carcinoma in a patient previously treated with mantle-field radiation therapy for Hodgkin lymphoma.

BACKGROUND: Radiation-induced salivary gland tumors are well described in the literature, with mucoepidermoid cancer being the most common histologic entity. Epithelial-myoepithelial carcinoma is a rare tumor accounting for <1% of all tumors in the salivary glands. METHODS AND RESULTS: We describe the first case of radiation-induced epithelial-myoepithelial carcinoma in the English-language medical literature. A 48-year-old man presented with right-sided mandibular pain and trismus, 25 years after mantle-field radiation therapy (RT) for Hodgkin lymphoma. He underwent excision of a right submandibular mass, which revealed a diagnosis of epithelial-myoepithelial carcinoma. Although typically a low-grade tumor, the histology revealed extensive necrosis and high mitotic activity. The patient required multiple resections and adjuvant therapy after multiple recurrences over a 4-year period. CONCLUSION: Reports of epithelial-myoepithelial carcinoma are relatively rare and this case highlights the importance of long-term follow-up and increased awareness of the risks of salivary gland tumors in this population.

Follicular adenoma with extensive extracellular mucin deposition: report on two cases.

We report two cases of follicular adenoma of the thyroid with extensive extracellular mucin deposition. Fine needle aspiration in Case 1 showed singly discohesive polygonal cells in a granular mucinous background. They contained abundant eosinophilic cytoplasm, nuclear irregularities, and frequent nuclear inclusions with occasional bizarre mitoses. A right lobectomy was done. In Case 2, a 47-year-old Caucasian woman with multinodular goiter had total thyroidectomy and a yellow-tan nodule was found within the right lobe. Both tumors were well-encapsulated masses with thick capsules. Each was characterized by microfollicles without papillae in a mucinous stroma. Tumor cells were positive for thyroglobulin and negative for calcitonin, CEA, galectin-3, HBME-1, and CK19. The extracellular mucin stained with Alcian-blue and colloidal iron but not with mucicarmine and D-PAS. No BRAF gene mutation was detected. Because there were neither capsular nor vascular invasions, both cases were diagnosed as follicular adenomas of the thyroid with extensive extracellular mucin deposition, which as proposed by the WHO classification can be categorized as a mucinous variant of follicular adenoma. Retrospectively, frequent nuclear inclusions and the absence of nuclear grooves in the mucin-containing background of cytologic smears and histologic sections were shared by those of mucin-producing papillary carcinoma. It is unclear whether it belongs to an existing category of thyroid neoplasm with mucin production or whether it is truly a new tumor variant. Furthermore, pathologists should pay attention to avoid misdiagnosis of this variant of follicular neoplasm that shows an overlapping cytology with that of papillary carcinoma.

PAX2 and PAX8 expression in primary and metastatic renal tumors: a comprehensive comparison.

CONTEXT: The diagnosis of renal cell carcinoma (RCC) remains problematic, especially in the context of metastasis or small-needle biopsies. PAX2 and PAX8 transcription factors are known to be expressed by several histologic types of renal neoplasms. OBJECTIVE: To evaluate the diagnostic utility of PAX2 and PAX8 relative to one another, which has not been studied. DESIGN: Consecutive tissue sections from the archival samples of 243 primary and 99 metastatic renal neoplasms were submitted to PAX2 and PAX8 immunostain. RESULTS: Within the primary neoplasms, PAX2 versus PAX8 expression was noted in 90 of 95 (95%) versus 92 of 95 (97%) for clear cell RCC, 29 of 38 (76%) versus 38 of 38 (100%) for papillary RCC, 14 of 25 (56%) versus 22 of 25 (88%) for chromophobe RCC, 3 of 7 (43%) versus 5 of 7 (71%) for collecting duct RCC, 6 of 8 (75%) versus 8 of 8 (100%) for acquired cystic kidney disease-related RCC, and 7 of 13 (54%) versus 11 of 13 (85%) for oncocytoma. Regardless of histologic subtype, PAX8 staining was noted in more cells and with more intense staining than PAX2. Within the metastatic RCCs, PAX8 expression was more frequently positive than PAX2 expression (88 of 99 cases; 89%; versus 75 of 99 cases; 76%). CONCLUSIONS: Both PAX2 and PAX8 are diagnostically useful markers for both primary and metastatic renal neoplasms of a large variety of histologic types. However, PAX8 appears to be more sensitive than PAX2 in both primary and metastatic settings. PAX8 can be included in any immunohistochemical panel for the diagnosis of primary renal neoplasms. Adding PAX2 should be optional, but this would gain limited further diagnostic yield. In a metastatic setting, both PAX8 and PAX2 can be included in a panel because a small subset of metastatic RCCs are stained only with PAX2.

IgG4-related inflammatory pseudotumor of the central nervous system responsive to mycophenolate mofetil.

Orbital apex and skull base masses often present with neuro-ophthalmic signs and symptoms. Though the localization of these syndromes and visualization of the responsible lesion on imaging is typically straightforward, definitive diagnosis usually relies on biopsy. Immunohistochemistry is important for categorization and treatment planning. IgG4-related disease is emerging as a pathologically defined inflammatory process that can occur in multiple organ systems. We present two patients with extensive inflammatory mass lesions of the central nervous system with immunohistochemistry positive for IgG4 and negative for ALK-1 as examples of meningeal based IgG4-related inflammatory pseudotumors. In both patients, there was treatment response to mycophenolate mofetil.

Molecular characterization of an EWSR1-POU5F1 fusion associated with a t(6;22) in an undifferentiated soft tissue sarcoma.

We report a soft tissue sarcoma from the thigh with morphologic features resembling Ewing sarcoma, clear cell sarcoma, and myoepithelial tumor of soft tissue. In addition, the genetic and immunohistochemical findings do not correspond to any established pattern, so the tumor does not clearly fit into any one classification. The karyotype analysis revealed a rare chromosomal rearrangement, t(6;22)(p22;q12), that previously has been reported in bone and epithelial tumors. Molecular studies confirmed the presence of an EWSR1-POU5F1 fusion creating a chimeric gene with the N-terminal transcriptional activation domain of EWSR1 and the C-terminal POU DNA binding domain of POU5F1. This report is novel in that to our knowledge, it is the first complete molecular characterization of an EWSR1-POU5F1 fusion in a soft tissue sarcoma. Evaluation of existing data on the known EWSR1-POU5F1 tumors suggests that the fusion gene functions in a wide variety of cell types and may modify the differentiation state of cells, resulting in susceptibility to tumorigenesis.

p63 expression in giant cell-containing lesions of bone and soft tissue.

CONTEXT: Previous studies have demonstrated p63 overexpression in giant cell tumors of bone and advocate its use as a potential diagnostic marker. Although routine histology is often all that is required to diagnose giant cell tumor of bone, immunohistochemistry could prove useful to distinguish it from other benign and malignant giant cell-containing lesions of bone and soft tissue on needle biopsies and unusual clinical settings. OBJECTIVE: To assess p63 expression in giant cell-containing lesions of bone and soft tissue. DESIGN: p63 immunohistochemistry was performed in 23 giant cell tumors of bone, 8 primary aneurysmal bone cysts, 12 chondroblastomas, 4 giant cell reparative granulomas, 4 osteosarcomas, 15 tenosynovial giant cell tumors, 6 nonossifying fibromas, and 4 pigmented villonodular synovitides. RESULTS: p63 overexpression was identified in 20 of 23 giant cell tumors of bone (86.9%), 5 of 8 primary aneurysmal bone cysts (62.5%), 10 of 12 chondroblastomas (83.3%), 4 of 4 giant cell reparative granulomas (100%), 2 of 4 osteosarcomas (50%), 1 of 15 tenosynovial giant cell tumors (6.6%), 1 of 6 nonossifying fibromas (16.6%), and 1 of 4 pigmented villonodular synovitides (25%). The sensitivity, specificity, positive predictive value, and negative predictive value of p63 immunohistochemistry for the diagnosis of giant cell tumor of bone were 86.95%, 53.36%, 45.45%, and 91.17%, respectively. CONCLUSIONS: This study shows that although p63 is expressed by most giant cell tumors of bone, its lack of specificity limits its use as an immunohistochemical marker in the differential diagnosis of giant cell-containing lesions of bone and soft tissue.

Updating the prostate cancer risk indicator for contemporary biopsy schemes.

INTRODUCTION AND OBJECTIVE: The prostate cancer risk indicator is a validated tool for predicting the chance of a screen detected prostate cancer to be classified as indolent, partially based on lateralized sextant biopsies. Our objective is to extract correction factors for adjustment of the model, addressing contemporary extended biopsy schemes. MATERIALS AND METHODS: Post-mortem 18-core biopsy results of men who died of unrelated causes, but were diagnosed with prostate cancer post-mortem were used to provide details on prostate biopsies and whole mount specimens. For each of the 18-core biopsies showing cancer, Gleason score, number of positive cores, location in the gland and percentage of cancer involvement were determined and correlated to final pathology. Total length of cancer tissue in a 6-core scheme was related to the length in 12 and 18-core schemes to compute correction factors. Furthermore, upgrading on extended biopsies and final pathology was evaluated. RESULTS: Data from 33 autopsied men were included. The 18 and 12-core biopsies showed 192.72 mm and 143.76 mm of prostate cancer, compared to 70.80 mm with lateralized sextant biopsy, resulting in correction factors of 2.72 and 2.03 for 18 and 12-core schemes respectively. Upgrading in Gleason score on extended biopsy regimens compared to lateralized sextant biopsy occurred in 33% (11/33) of the cases. CONCLUSION: Based on autopsy data, the present correction factors provide a support in the adjustment of the prostate cancer risk indicator towards more extended contemporary biopsy schemes, eventually leading to a more accurate prediction of the probability of indolent cancers and assisting patients and clinicians to make appropriate choices in daily practice.

Newly described translocation (18;19)(q23;q13.2) in abdominal wall soft-tissue tumor resembling Ewing sarcoma/primitive neuroectodermal tumor.

From a morphologic standpoint, Ewing sarcoma (EWS) is one of a number of pediatric malignancies that are characterized by sheets of small, round, blue cells. Ewing sarcoma can usually be differentiated from other small round blue cell tumors by the presence of a gene rearrangement having a consistent breakpoint within the Ewing sarcoma gene (EWSR1) at 22q12. Although the most common translocation partner is FLI1, located at 11q24, there is a growing list of alternate rearrangements involving different loci. We describe the first example of a soft-tissue sarcoma morphologically and immunohistochemically similar to Ewing sarcoma, but with a novel t(18;19)(q23;q13.2).