Androgen receptor expression is usually maintained in initial surgically resected breast cancer metastases but is often lost in end-stage metastases found at autopsy

Androgen receptor (AR) is expressed in approximately 70% of primary breast carcinomas (PBCs) and is a promising therapeutic target for metastatic breast carcinoma (MBC). Here, we examine AR expression in a population of initial surgically resected metastases and a separate cohort of end-stage metastases harvested at autopsy compared with their matched PBCs. Tissue microarrays of matched PBC and MBC were labeled by immunohistochemistry for AR, estrogen receptor (ER), progesterone receptor (PR), and Her2 and classified into the following previously described categories: luminal (ER/PR+/Her2-), triple negative (ER/PR/Her2-), Her2 (ER/PR-/Her2+), and luminal loss (ER/PR loss from primary to metastasis). In the cohort of surgically resected metastases (n = 16), AR was expressed in 12 of 16 PBC and maintained in 11 of 12 corresponding MBCs. Of these, 36% showed stronger AR labeling in the metastases and none showed a decrease. In the cohort of metastases harvested at autopsy (n = 16), AR was expressed in 11 of 16 primary carcinomas and maintained in only 5 of 11 corresponding metastases. Of these, none showed increased AR and 80% showed decreased AR labeling. AR expression is overwhelmingly concordant between matched PBC and MBC at initial presentation. These findings validate AR as a therapeutic target in MBC and suggest that AR may need to be reevaluated in metastases even if the primary is negative. However, similar to ER/PR, AR expression is often decreased with a trend toward complete loss in end-stage metastases, suggesting a shift of AR expression between initial and end-stage metastases. This suggests an opportunity for targeted antiandrogen therapy at an earlier stage of disease progression.     

Use of computerized assessment to predict neuropsychological functioning and emotional distress in patients with systemic lupus erythematosus

OBJECTIVE: Cognitive dysfunction and neuropsychiatric disturbance are common in systemic lupus erythematosus (SLE). This study addressed the ability of the Automated Neuropsychological Assessment Metrics (ANAM), a computerized cognitive testing battery consisting of cognitive subtests, a sleepiness rating scale, and a mood scale, to predict neuropsychological status in patients with SLE. METHODS: Sixty individuals with SLE and no overt neuropsychiatric symptoms were administered ANAM to determine its validity as a screening measure of cognitive dysfunction and emotional distress in SLE. RESULTS: Performance on ANAM was compared with results of a consecutively administered, 2-hour battery of traditional neuropsychological tests and the Beck Depression Inventory II (BDI-II). Individual ANAM cognitive test scores were significantly correlated with most neuropsychological tests, particularly those measuring psychomotor processing speed and executive functioning. Using logistic regression, ANAM cognitive subtests successfully predicted individuals with SLE who had probable versus no impairment after controlling for premorbid levels of cognitive ability. Sensitivity of group classification was 76.2% and specificity was 82.8%, with 80% correct classification overall. ANAM's ability to predict neuropsychological functioning remained even after controlling for subjective reports of depressed mood and current sleepiness. Further, the ANAM mood scale was significantly correlated with the BDI-II (r = 0.67, P < 0.001), indicating its potential future use as a screening tool for emotional distress. CONCLUSION: ANAM shows promise as a time- and cost-efficient tool for screening and monitoring cognitive and emotional functioning in SLE, and can indicate when a more thorough neuropsychological investigation is warranted.     

Atypical granular cell tumor of the thyroid: cytomorphologic features on fine needle aspiration

Granular cell tumors are uncommon soft tissue neoplasms of nerve sheath origin, which are predominately benign and are characterized by abundant granular cytoplasm, uniform nuclei, and indistinct cell borders. Features of malignancy include spindle cell morphology, necrosis, prominent nucleoli, increased nuclear to cytoplasmic ratio, nuclear pleomorphism, and increased mitotic rate. Granular cell tumors are most common in the soft tissues of the head and neck, but have only been rarely described in the thyroid gland. Here we report a case of an atypical granular cell tumor of the thyroid seen on fine needle aspiration, which displayed focal atypical cells with spindle cell morphology, increased nuclear to cytoplasmic ratio, and prominent nucleoli. The differential diagnosis of such findings is also presented.