Variability in endometrial carcinoma pathology practice: opportunities for improvement with molecular classification.

We assessed the landscape of diagnostic pathology practice and how molecular classification could potentially impact management of patients with endometrial cancer by collecting patient samples, clinicopathologic data, and patient outcomes from EC patients diagnosed in 2016 at 10 Canadian tertiary cancer centers and 19 community hospitals. ProMisE molecular subtype (POLEmut, MMRd, p53abn, No Specific Molecular Profile (NSMP)) was assigned retrospectively. 1357 patients were fully evaluable including 85 POLEmut (6.3%), 380 MMRd (28.0%), 643 NSMP (47.4%), and 249 p53abn ECs (18.3%). Immunohistochemistry (IHC) for MMR proteins was undertaken at the time of primary diagnosis in 2016 in only 42% of the cohort (570/1357; range 3.5-95.4%/center). p53 IHC had only been performed in 21.1% of the cohort (286/1357; range 10.1-41.9%/center). Thus, based on the retrospective molecular subtype assignment, 54.7% (208/380) of MMRd EC had not been tested with MMR IHC (or MSI) and 48.2% (120/249) of p53abn ECs were not tested with p53 IHC in 2016. Molecular subtype diversity within histotypes was profound; most serous carcinomas were p53abn (91.4%), but only 129/249 (51.8%) p53abn EC were serous. Low-grade (Gr1-2) endometrioid carcinomas were mostly NSMP (589/954, 61.7%) but included all molecular subtypes, including p53abn (19/954, 2.0%). Molecular subtype was significantly associated with clinical outcomes (p < 0.001) even in patients with stage I disease (OS p = 0.006, DSS p < 0.001, PFS p < 0.001). Assessment of national pathologic practice in 2016 shows highly variable use of MMR and p53 IHC and demonstrates significant opportunities to improve and standardize biomarker reporting. Inconsistent, non-reflexive IHC resulted in missed opportunities for Hereditary Cancer Program referral and Lynch Syndrome diagnosis, and missed potential therapeutic implications (e.g., chemotherapy in p53abn EC, immune blockade for MMRd EC). Routine integration of molecular subtyping into practice can improve the consistency of EC pathology assessment and classification.

Successful treatment of hepatic oligometastases with stereotactic ablative radiotherapy and radiofrequency ablation in an anaplastic lymphoma kinase fusion-positive lung cancer patient.

Local ablative therapy with stereotactic ablative radiotherapy may improve survival in oncogene-addicted lung cancer patients with extracranial oligometastatic disease treated with targeted therapies. There is limited data on the use of radiofrequency ablation (RFA) in this same setting. We present a case of an anaplastic lymphoma kinase (ALK)-positive lung cancer patient with hepatic oligometastatic progression who was successfully treated with both stereotactic ablative radiation and RFA while continuing with an ALK inhibitor.

Microchimerism in the rheumatoid nodules of patients with rheumatoid arthritis.

OBJECTIVE: The rheumatoid nodule is a lesion commonly found on extraarticular areas prone to mechanic trauma. When present with inflammatory symmetric polyarthritis, it is pathognomonic of rheumatoid arthritis (RA), an autoimmune disease in which naturally acquired microchimerism has previously been described and can sometimes contribute to RA risk. Since RA patients harbor microchimerism in the blood, we hypothesized that microchimerism is also present in rheumatoid nodules and could play a role in rheumatoid nodule formation. This study was undertaken to investigate rheumatoid nodules for microchimerism. METHODS: Rheumatoid nodules were tested for microchimerism by real-time quantitative polymerase chain reaction (qPCR). The rheumatoid nodules of 29 female patients were tested for a Y chromosome-specific sequence. After HLA genotyping of patients and family members, rheumatoid nodules from 1 man and 14 women were tested by HLA-specific qPCR, targeting a nonshared HLA allele of the potential microchimerism source. Results were expressed as genome equivalents of microchimeric cells per 10(5) patient genome equivalents (GE/10(5)). RESULTS: Rheumatoid nodules from 21% of the female patients contained male DNA (range <0.5, 10.3 GE/10(5)). By HLA-specific qPCR, 60% of patients were microchimeric (range 0, 18.5 GE/10(5)). Combined microchimerism prevalence was 47%. A fetal or maternal source was identified in all patients who tested positive by HLA-specific qPCR. Unexpectedly, a few rheumatoid nodules also contained microchimerism without evidence of a fetal or maternal source, suggesting alternative sources. CONCLUSION: Our findings indicate that microchimerism is frequently present in the rheumatoid nodules of RA patients. Since microchimerism is genetically disparate, whether microchimerism in rheumatoid nodules serves as an allogeneic stimulus or allogeneic target warrants further investigation.

Synchronous metastatic seminoma and primary retroperitoneal ganglioneuroma: case report and literature review.

Testicular cancer is the most common malignancy in young men with seminomas comprising almost half of all germ cell tumours. Benign ganglioneuromas are rare tumours derived from the sympathetic nervous system. They usually occur in aldolescents and young adults and are predominantly located in the mediastinum and retroperitoneum. We report a case of a patient with synchronous metastatic testicular seminoma with retroperitoneal lymph node involvement and a benign retroperitoneal ganglioneuroma (RGN) which caused diagnostic and management challenges. The patient had a complete response following combination chemotherapy for his seminoma and subsequently underwent complete resection of his ganglioneuroma.

Tuberculosis of the bladder without previous renal infection.

Tuberculous (TB) infections are usually limited to the pulmonary system but the hematogenous spread of TB can result in secondary infections in any part of the body. Genitourinary TB is uncommon and follows hematogenous spread from a primary pulmonary infection to the kidneys. A rare case of a TB infection of the bladder without renal involvement is described.

Treatment of invasive breast carcinoma with ultrasound-guided radiofrequency ablation.

BACKGROUND: Radiofrequency ablation (RFA) is a minimally invasive thermal ablation technique. This study reports the safety and efficacy of RFA as a minimally invasive strategy for breast cancers <3 cm diameter in postmenopausal women. METHODS: Twenty-two postmenopausal women (aged 60 years or older) with clinical T-1N0 core biopsy proven breast cancers were studied. Thermocoagulation was undertaken using a sonographically guided RF probe under local anesthesia and sedation. The ablated tumor was resected between 1 and 2 weeks later. Endpoints were technical success, completeness of tumor kill, marginal clearance, skin damage, and patient reports of pain and procedural acceptability. RESULTS: The procedure was well tolerated and cosmesis was excellent. Pathology revealed a central ablation zone surrounded by hyperemia. Coagulative necrosis was complete in 19 of 22 patients. Disease at the ablation zone margin was found in 3 patients and 5 patients had disease distant to the ablation zone consisting of multifocal tumors (2), in-transit metastasis (1), and extensive ductal carcinoma in situ with microinvasive carcinoma (2). Ninety-five percent of patients would be willing to have RFA again. CONCLUSIONS: Radiofrequency ablation can be safely applied in an outpatient setting with acceptable patient tolerance. By itself, RFA cannot be considered effective local therapy. Trials to evaluate RFA complemented with breast irradiation are justified.