Breast Cancer With HER2 Immunohistochemical Score 2 and Average HER2 Signals/Cell 6 or More and HER2/CEP17 Ratio Less Than 2 ('ISH Group 3'): A Multiinstitutional Cohort Analysis Emphasizing Outcome and Molecular Subtype.

Breast cancer (BC) with average human epidermal growth factor receptor 2 (HER2) signals/cell ≥6 and HER2/chromosome enumeration probe 17 (CEP17) ratio <2 (in situ hybridization [ISH] group 3) is very rare, accounting for 0.4% to 3.0% of cases sent for the dual-probe ISH assay. Although such patients are currently eligible for treatment with HER2-targeted therapy, their characteristics and outcomes remain poorly understood. Sixty-two BCs with equivocal HER2 immunohistochemical score (2+) and reflex ISH group 3 results were identified across 4 institutions. Available clinicopathologic characteristics, MammaPrint and BluePrint molecular results, and follow-up information were retrospectively analyzed. Most BCs with HER2 equivocal immunohistochemical and ISH group 3 results were histologic grade 2 or 3 (100%), estrogen receptor (ER) positive (90.3%), with an average HER2 signals/cell of 7.3. Molecular profiles revealed that 80% (16/20) of tumors were luminal subtypes, and HER2 molecular subtype was identified in 10% of tumors (2/20). Twelve (19.4%) out of 62 patients developed local recurrence and/or distant metastasis with a median follow-up of 50 months. One (10%) of 10 patients achieved pathologic complete response after neoadjuvant chemotherapy. Forty-nine (79%) out of 62 patients completed anti-HER2 agents, and exploratory analysis showed no statistically significant difference in disease outcomes between patients who completed anti-HER2 treatment and those who did not. Univariate analysis revealed advanced clinical stage, and ER/progesterone receptor negativity was associated with unfavorable disease outcomes, and exploratory multivariate analysis demonstrated that clinical stage was the most significant factor associated with disease outcomes in the studied population. These findings increase our understanding of this rare, but clinically important HER2 category. Large-scale prospective randomized studies are needed to further evaluate the role of perioperative HER2-targeted therapy in this patient population.

Applying the New Guidelines of HER2 Testing in Breast Cancer.

PURPOSE OF REVIEW: The human epidermal growth factor receptor 2 (HER2) is an important prognostic and predictive biomarker in the breast cancer. The American Society of Clinical Oncology/College of American Pathology (ASCO/CAP) has published HER2 testing guidelines in breast cancer. We herein reviewed the HER2 testing guidelines in breast cancer with a focus on the application of the current guidelines. RECENT FINDINGS: The continual investigation of HER2 testing in breast cancer has resulted in updates in the HER2 testing guidelines. The current guidelines focus on the uncommon clinical scenarios and emphasize the coordination between immunohistochemistry and in situ hybridization results, in an effort to improve clarity and accuracy. The ASCO/CAP guidelines provide valuable recommendations to ensure the accurate evaluation of HER2 status in breast cancer patients through standardization. Additional studies, particularly those with long-term outcome data are still needed to validate the guideline recommendations, especially the uncommon cases.

Myositis ossificans in the chest wall: A case report.

Myositis ossificans is delineated and distinguished by the generation and deposition of cartilaginous and osseous soft tissues. It generally occurs in the lower extremities and is caused by direct trauma. During the different developmental stages of maturation, the lesion has different radiological appearances that can be confused with sarcomas. Here, we present the case of a 38-year-old woman who presented to the outpatient clinic with a painful mass in the lateral chest wall that had rapidly expanded and increased in size. The patient had no history of trauma. Chest computed tomography revealed an intramuscular mass in the lateral chest wall; postcontrast images demonstrated heterogeneous enhancement and peripheral calcification. The patient was then referred to our center for subsequent assessment and examinations. Pathological examination findings confirmed the diagnosis of myositis ossificans. Surgical resection was performed after obtaining patient consent. The symptoms experienced by the patient were successfully relieved, and no evidence of recurrence was observed during the 2-year follow-up period. Knowledge of the atypical locations of myositis ossificans, calcification patterns at different stages, and radiopathological correlations can help accurately diagnose myositis ossificans and avoid unnecessary medical imaging and interventions.

Intraligamentous synovial osteochondroma of the ligamentum teres: a series of 14 cases.

BACKGROUND: The ligamentum teres (LT) is covered by synovium. It acts as a stabilizer of the hip and as such it has been compared to the ACL of the knee joint. Pathologic changes occur in the LT with aging and osteoarthritis (OA), including degeneration, occasional chondroid metaplasia, and synovial chondromatosis are well-recognized in the literature. However, there are no reports of intraligamentous synovial osteochondroma occuring in the LT. METHODS: We reviewed the pathology reports of 542 osteoarthritic femoral arthroplasty specimens between January 2016 and December 2018. The LT was examined histologically in 55 cases because it was abnormal on gross examination. RESULTS: A single synovial osteochondroma, ranging in size from 0.4-1.7 cm in diameter, was present in the body of the LT in 14 cases (9 males; 5 females, aged 34 to 81 years), representing 2.6% of 542 arthroplasty cases. Ten of the osteochondromas had bone marrow fat without hematopoietic elements, 1 had hematopoietic elements, and 3 had no marrow among the bony trabeculae. Radiographically, all cases had moderate to severe osteoarthritis with no mention of an abnormality of LT. CONCLUSION: To our knowledge, this is the first report of intraligamentous synovial osteochondroma in the LT in osteoarthritis patients undergoing hip arthroplasty. It provides further support for microscopic examination of arthroplasty specimens for histologic abnormalities. Further prospective study is needed to determine if this lesion contributes adversely to the development or progression of osteoarthritis and if it is a reactive or neoplastic process.

Cytospin performance when using Paris system for reporting urinary cytology.

Objectives: The Paris System (TPS) for Reporting Urine Cytology has significantly improved the approach to evaluating urine cytology. TPS criteria were defined mainly according to ThinPrep and SurePath preparations, as they are widely utilized. The objective of this study is to validate urine cytology interpretation according to the TPS classification using cytospin technique in relation to the gold slandered histology. Material and Methods: This retrospective study examined and analyzed 316 urine specimens from King Abdulaziz University Hospital between 2015 and 2020. Cytospin technique is performed for all cases. Slides were recategorized using TPS criteria, then compared with the original histology diagnosis. Results: According to the TPS, 108 cases were classified as 101 AUC (32%), 95 NEG (30%), 59 HGUC (18.7%), 31 SHGUC (9.8%), and 30 (9.5%) others. The computed sensitivity of cytospin in urine cytology was 94.7%, with 73.9% specificity, a positive predictive value of 85.6%, a negative predictive value of 89.5%, and overall accuracy of 86.8%. Conclusion: Urine cytology testing is considered to be a non-invasive and sensitive method to screen for urothelial carcinoma. TPS defined standards are reliable on cytospin prepared slides for reporting urine cytology.

Histiocytic Sarcoma Arising From a Long Bone: Report of Two Cases.

Histiocytic sarcoma is a rare, but aggressive malignant neoplasm of monocyte/macrophage lineage with a wide age distribution. Bone involvement is exceedingly rarer compared to the lymph node, skin, and soft tissue, and no long bone involvement has been reported in the English literature. We here report 2 cases of histiocytic sarcoma involving the long bone: one from the femur of a 77-year-old female, status post the placement of an intramedullary nail for subtrochanteric hip fracture; the other from the radius of a 3-year-old female with no significant medical history. Radiologic imaging showed highly destructive lesions in both cases with soft-tissue extension. Microscopy in both cases showed sheets of polygonal mononuclear cells with abundant eosinophilic cytoplasm, prominent nucleoli, and frequent mitosis. Hemophagocytosis were also identified. Immunohistochemistry showed that the lesional cells were strongly diffusely positive for CD68 and CD163. The first patient deteriorated rapidly, despite the aggressive treatment of amputation and chemotherapy. However, the second patient is disease free 36 months post the treatment of amputation only. We conclude that the long bone could be the primary site of histiocytic sarcoma. Its prognosis could be very variable and it is difficult to predict its behavior based on morphological evaluation only.

Surgical management of aggressive hemangiomas of the spine.

Our objective is to describe the surgical management and outcomes following surgical intervention for aggressive spine hemangiomas. Patients from 2005 to 2018 with an aggressive hemangioma of the cervical, thoracic, lumbar spine and sacrum treated surgically at a tertiary referral academic medical center were included in this study. The hospital pathology department database was used to identify patients with a diagnosis of aggressive hemangioma. Patient demographics, medical history, operative procedure, adjunct treatment, early and late complications, and recurrence were analyzed using the Fischer exact test with significance set at p < 0.05 Ten patients met inclusion criteria for the study. The average follow up was 11 months. Eight out of ten patients had aggressive hemangioma of the thoracic spine. Seven of the ten patients presented with back or leg pain. The most common surgery was laminectomy at the site of the lesion (70%). 40% of patients underwent a spinal fusion, with two of these patients receiving concurrent intra-operative vertebroplasty. Three patients underwent post-operative radiation therapy. Five complications were noted among three individuals. There were three perioperative complications, deep venous thrombosis, renal insufficiency, one surgical site infection, and two postoperative complications, both revisions. There were no recurrences. Surgical intervention for aggressive spine hemangiomas is an effective treatment with relatively low complication and recurrence rates.

Frequency, Clinicopathologic Characteristics, and Follow-up of HER2-Positive Nonpleomorphic Invasive Lobular Carcinoma of the Breast.

OBJECTIVES: To investigate human epidermal growth factor receptor 2 (HER2)-positive nonpleomorphic invasive lobular carcinoma (ILC), which has rarely been addressed. METHODS: Clinicopathologic characteristics and follow-up of HER2-positive nonpleomorphic ILCs were collected and compared to those of HER2-negative counterparts. RESULTS: Twenty-one cases of HER2-positive nonpleomorphic ILCs were identified, 6.3% of the study population. Compared to HER2-negative nonpleomorphic ILC, patients with HER2 positivity were older (P < .05), likely to be hormonal receptor negative (P < .01), and had higher histologic grade and angiolymphatic invasion (P < .01). HER2 positivity in nonpleomorphic ILCs was associated with higher recurrence/metastasis with hazard ratio of 2.03 (P < .05). No patient who received neoadjuvant therapy achieved pathologic complete response, and HER2-targeted therapy tended to reduce recurrence/metastasis in patients with HER2-positive nonpleomorphic ILC. CONCLUSIONS: Our results highlight the existence of HER2 positivity in nonpleomorphic ILCs and reinforce that HER2 is associated with worse prognosis in nonpleomorphic ILC.