Granular cell tumor of distal bile duct treated with Whipple's procedure.

Granular cell tumors (GCTs) are rare benign neoplasms that are most often located in the soft tissues of the extremities and chest wall. Malignant GCTs have also been reported. GCTs of the biliary tract are extremely rare, uncommon non-epithelial benign neoplasms that cause focal thickening of bile duct wall without mucosal invasion. They consist of polygonal cells with granular appearance and stain positive in S-100 protein, indicating a neural (Schwann cell) origin. We report our experience of a 57-year-old Caucasian woman who presented with obstructing jaundice due to a distal bile duct stricture highly suspicious of cholangiocarcinoma. A Whipple's procedure was successfully performed, and the final pathology revealed a benign GCT of the distal bile duct. Whipple's is an extremely radical procedure for such benign lesions and additional investigations, such as cytology sample, may result in a less aggressive approach as those tumors grow slowly and do not metastasize.

Vaccinated and Convalescent Donor-Derived Severe Acute Respiratory Syndrome Coronavirus 2-Specific T Cells as Adoptive Immunotherapy for High-Risk Coronavirus Disease 2019 Patients.

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic poses an urgent need for the development of effective therapies for coronavirus disease 2019 (COVID-19). METHODS: We first tested SARS-CoV-2-specific T-cell (CοV-2-ST) immunity and expansion in unexposed donors, COVID-19-infected individuals (convalescent), asymptomatic polymerase chain reaction (PCR)-positive subjects, vaccinated individuals, non-intensive care unit (ICU) hospitalized patients, and ICU patients who either recovered and were discharged (ICU recovered) or had a prolonged stay and/or died (ICU critical). CoV-2-STs were generated from all types of donors and underwent phenotypic and functional assessment. RESULTS: We demonstrate causal relationship between the expansion of endogenous CoV-2-STs and the disease outcome; insufficient expansion of circulating CoV-2-STs identified hospitalized patients at high risk for an adverse outcome. CoV-2-STs with a similarly functional and non-alloreactive, albeit highly cytotoxic, profile against SARS-CoV-2 could be expanded from both convalescent and vaccinated donors generating clinical-scale, SARS-CoV-2-specific T-cell products with functional activity against both the unmutated virus and its B.1.1.7 and B.1.351 variants. In contrast, critical COVID-19 patient-originating CoV-2-STs failed to expand, recapitulating the in vivo failure of CoV-2-specific T-cell immunity to control the infection. CoV-2-STs generated from asymptomatic PCR-positive individuals presented only weak responses, whereas their counterparts originating from exposed to other seasonal coronaviruses subjects failed to kill the virus, thus disempowering the hypothesis of protective cross-immunity. CONCLUSIONS: Overall, we provide evidence on risk stratification of hospitalized COVID-19 patients and the feasibility of generating powerful CoV-2-ST products from both convalescent and vaccinated donors as an "off-the shelf" T-cell immunotherapy for high-risk patients.

The Expression and Prognostic Impact of Immune Cytolytic Activity-Related Markers in Human Malignancies: A Comprehensive Meta-analysis.

BACKGROUND: Recently, immune-checkpoint blockade has shown striking clinical results in different cancer patients. However, a significant inter-individual and inter-tumor variability exists among different cancers. The expression of the toxins granzyme A (GZMA) and perforin 1 (PRF1), secreted by effector cytotoxic T cells and natural killer (NK) cells, were recently used as a denominator of the intratumoral immune cytolytic activity (CYT). These levels are significantly elevated upon CD8+ T-cell activation as well as during a productive clinical response against immune-checkpoint blockade therapies. Still, it is not completely understood how different tumors induce and adapt to immune responses. METHODS: Here, we calculated the CYT across different cancer types and focused on differences between primary and metastatic tumors. Using data from 10,355, primary tumor resection samples and 2,787 normal samples that we extracted from The Cancer Genome Atlas and Genotype-Tissue Expression project databases, we screened the variation of CYT across 32 different cancer types and 28 different normal tissue types. We correlated the cytolytic levels in each cancer type with the corresponding patient group's overall survival, the expression of several immune-checkpoint molecules, as well as with the load of tumor-infiltrating lymphocytes (TILs), and tumor-associated neutrophils (TANs) in these tumors. RESULTS: We found diverse levels of CYT across different cancer types, with highest levels in kidney, lung, and cervical cancers, and lowest levels in glioma, adrenocortical carcinoma (ACC), and uveal melanoma. GZMA protein was either lowly expressed or absent in at least half of these tumors; whereas PRF1 protein was not detected in almost any of the different tumor types, analyzing tissue microarrays from 20 different tumor types. CYT was significantly higher in metastatic skin melanoma and correlated significantly to the TIL load. In TCGA-ACC, skin melanoma, and bladder cancer, CYT was associated with an improved patient outcome and high levels of both GZMA and PRF1 synergistically affected patient survival in these cancers. In bladder, breast, colon, esophageal, kidney, ovarian, pancreatic, testicular, and thyroid cancers, high CYT was accompanied by upregulation of at least one immune-checkpoint molecule, indicating that similar to melanoma and prostate cancer, immune responses in cytolytic-high tumors elicit immune suppression in the tumor microenvironment. CONCLUSION: Overall, our data highlight the existence of diverse levels of CYT across different cancer types and suggest that along with the existence of complicated associations among various tumor-infiltrated immune cells, it is capable to promote or inhibit the establishment of a permissive tumor microenvironment, depending on the cancer type. High levels of immunosuppression seem to exist in several tumor types.

Renal cell carcinoma with bilateral synchronous adrenal gland metastases: a case report.

INTRODUCTION: Renal cell carcinoma is characterized by its potential of metastasizing widely and to unusual sites, with the metastases occasionally preceding clinical recognition of the primary tumor. Synchronous bilateral adrenal metastases from renal cell carcinoma, without other metastases, are rare and, to our knowledge, only 17 cases have been published in the literature to date. In general, patients with synchronous bilateral adrenal metastases from renal cell carcinoma have a poor prognosis. CASE PRESENTATION: We report a case of right-sided renal cell carcinoma with simultaneous bilateral adrenal metastases in a 58-year-old woman. The primary tumor was localized in the upper and mid pole of the kidney. The diagnosis was established preoperatively by abdominal ultrasound and computed tomography. Surgical treatment consisted of a right radical nephrectomy and bilateral adrenalectomy. Postoperative cortisone acetate replacement was instituted. The pathological findings of the right renal tumor showed clear cell carcinoma and both adrenal tumors showed the same pathology as the right renal tumor. There was no evidence of recurrence after 6 months of follow-up. CONCLUSION: Patients with bilateral synchronous adrenal metastases should be considered to have disseminated metastatic disease. However, good performance status, the presence of paraneoplastic syndrome and the alleviation of refractory pain are important reasons make an urologist to consider radical nephrectomy in renal cell carcinoma patient with metastases.