A pregnant dilemma: primary hyperparathyroidism due to parathyromatosis in pregnancy.

OBJECTIVE: To describe an exceedingly rare case of parathyromatosis in pregnancy and the limited medical treatment options available for such cases that are refractory to surgery. METHODS: Case presentation and description of clinical course with brief review of the literature. RESULTS: A 21-year-old woman with a history of 3.5 gland parathyroidectomy presented with severe hyperemesis during her first trimester of pregnancy and was found to have primary hyperparathyroidism attributable to parathyromatosis. We describe the diagnostic and management dilemmas associated with this case, which included localization of the culprit lesions, a technically challenging surgical resection and subsequent medical management with cinacalcet when symptomatic hypercalcemia recurred during the third trimester. To our knowledge, this is only the third report of the successful use of cinacalcet during pregnancy, and the first case report of parathyromatosis presenting during pregnancy. CONCLUSION: Cinacalcet was used safely and effectively during the third trimester of pregnancy to treat symptomatic hypercalcemia due to parathyromatosis.

Quantitative diagnosis of malignant pleural effusions by single-cell mechanophenotyping.

Biophysical characteristics of cells are attractive as potential diagnostic markers for cancer. Transformation of cell state or phenotype and the accompanying epigenetic, nuclear, and cytoplasmic modifications lead to measureable changes in cellular architecture. We recently introduced a technique called deformability cytometry (DC) that enables rapid mechanophenotyping of single cells in suspension at rates of 1000 cells/s-a throughput that is comparable to traditional flow cytometry. We applied this technique to diagnose malignant pleural effusions, in which disseminated tumor cells can be difficult to accurately identify by traditional cytology. An algorithmic diagnostic scoring system was developed on the basis of quantitative features of two-dimensional distributions of single-cell mechanophenotypes from 119 samples. The DC scoring system classified 63% of the samples into two high-confidence regimes with 100% positive predictive value or 100% negative predictive value, and achieved an area under the curve of 0.86. This performance is suitable for a prescreening role to focus cytopathologist analysis time on a smaller fraction of difficult samples. Diagnosis of samples that present a challenge to cytology was also improved. Samples labeled as "atypical cells," which require additional time and follow-up, were classified in high-confidence regimes in 8 of 15 cases. Further, 10 of 17 cytology-negative samples corresponding to patients with concurrent cancer were correctly classified as malignant or negative, in agreement with 6-month outcomes. This study lays the groundwork for broader validation of label-free quantitative biophysical markers for clinical diagnoses of cancer and inflammation, which could help to reduce laboratory workload and improve clinical decision-making.

Sinonasal undifferentiated carcinoma metastatic to the skin.

Sinonasal undifferentiated carcinoma (SNUC) is an aggressive malignancy of disputed histogenesis that arises in the sinonasal tract and has an extremely poor prognosis. Despite multimodality treatment with surgical resection, radiation, and chemotherapy, recurrence is common. The tumor spreads by direct local extension, but also metastasizes to lymph nodes, brain, lung and bone. To date, reports of metastasis to the skin have not been published. We report a case of a 58-year-old woman diagnosed with SNUC who underwent surgical resection of the tumor followed by chemoradiation. The tumor soon recurred, and she required wide re-excision. Two months after this procedure, she developed multiple dermal nodules in the head and neck region, clinically suspicious for metastases. Biopsy of a nodule from the right neck revealed a poorly differentiated carcinoma, with morphological and immunohistochemical findings consistent with a metastasis of the patient's known SNUC. We conclude that the skin may be a rare site of metastasis of SNUC, and in some cases may be the presenting sign of tumor recurrence despite aggressive multimodality treatment.

Mycobacterium tuberculosis/HIV-1 coinfection and disease: role of human leukocyte antigen variation.

Genetic variation influences immune responses and may contribute to differential development of tuberculosis (TB), particularly in immunosuppressed individuals. To examine the risk of Mycobacterium tuberculosis infection progressing to disease in the context of M. tuberculosis/human immunodeficiency virus (HIV) type 1 coinfection, HIV-1 RNA load and human leukocyte antigen (HLA) genotypes were determined among subjects from Harare, Zimbabwe, an area where both TB and HIV-1 are endemic. Patients with TB were compared with control subjects, stratified by HIV-1 infection status and progression of TB disease. Alleles of class I HLA-A and -C were associated with risk of developing active TB, depending on HIV-1 status. Among HIV-positive subjects, HIV-1 load was independently associated with increased risk of developing pulmonary TB. HLA DRB1 homozygosity among HIV-positive subjects was associated with reduced risk of developing pulmonary TB but increased risk of rapid progression to pleural effusion TB. These observations suggest that HLA plays a role in risk of developing symptomatic TB at various stages of disease and that these effects are modified by HIV-1 coinfection.