Humoral Response of Patients With Autoimmune Rheumatic Disease to BNT162b2 Vaccine: A Retrospective Comparative Study.

Objective The effectiveness and safety of SARS-CoV-2 vaccines in patients with autoimmune rheumatic diseases (ARDs) treated with immunomodulators remain uncertain. Therefore, this study aimed to evaluate whether the humoral immune response to the BNT162b2 vaccine differs between patients without and with ARDs treated with immunomodulators. Methods We retrospectively reviewed 3208 electronic medical records from the database of the Hamad Medical Corporation (HMC) outpatient rheumatology clinics to capture patients with ARDs and control patients without autoimmune inflammatory diseases. All patients who were SARS-CoV-2 infection-naïve, had received two doses of BNT162b2 vaccination, and had been serologically tested using Elecsys® anti-SARS-CoV-2 S immunoassays (Roche Holdings AG, Basel, Switzerland), were included in the analysis. Patients with ARD were classified into six subgroups according to the received ARD immunomodulators: methotrexate monotherapy (MTXM), a combination of conventional synthetic disease-modifying antirheumatic drugs (Cs-DMARDs), tumor necrosis factor inhibitor (TNF-i), rituximab, interleukin-6 inhibitor (IL6-i), and Janus kinase inhibitor (JAK-i). Samples with an anti-SARS-CoV-2 S titer of <0.8 and <132 binding antibody unit (BAU)/mL were defined as negative and poor seroconversion, respectively. The overall mean of anti-SARS-CoV-2 S titer and its level at <0.8 and <132 were compared between the six subgroups of patients with ARD and the controls by performing an unpaired t-test and Chi-squared or Fisher's exact test as appropriate. Results The mean (SD) age of 110 patients with ARDs and 20 controls was 47.1 (12) and 59.3 (8.9) years (P < 0.001), respectively, and women predominated both groups (60% vs. 75%, P = 0.20). The most frequently prescribed Cs-DMARDs was methotrexate in 50 (45.5%) patients, followed by TNF-i in 46 (41.8%), rituximab in 20 (18.2%), JAK-i in 12 (10.9%), and IL6-i in 7 (6.4%) patients. The mean (SD) anti-SARS-CoV-2 S antibody titer of only the rituximab subgroup significantly differed from the controls (P = 0.012). Conclusion The most prevalent ARD immunomodulators (Cs-DMARDs, TNF-i, JAK-i, and IL6-i) were associated with comparable seroconversion rates to the BNT162b2 vaccine. In comparison, rituximab was significantly associated with decreased immunogenicity.

IgG4-related disease mimicking pancreatic cancer: Case report and review of the literature.

INTRODUCTION: Most patients with pancreatic masses pose a diagnostic challenge when a benign lesion is suspected, and often, resection is needed before a benign diagnosis is confirmed. PRESENTATION OF CASE: A 57 years old male patient presented with a pancreatic head mass, obstructive jaundice and submandibular lymph node enlargement. He also had a history of recurrent eye pain and redness, skin lesions, and benign prostatic hypertrophy. MRI showed a pancreatic head mass with double duct sign, aortic thickening, bilateral renal lesions, diffuse lymph node enlargement, and prostatic enlargement. FDG-PET/CT demonstrated abnormal uptake corresponding to the MRI lesions, and there were elevated IgG4 levels on blood investigations. Biopsy of an inguinal lymph node revealed infiltrates with IgG4 plasma cells, consistent with the diagnosis of IgG4 disease. The patient was treated with IV steroids and showed significant improvement. DISCUSSION: IgG4 related disease is a rare entity that is characterized by lesions that show heavy infiltration with IgG4 positive plasma cells, storiform fibrosis, and obliterative phlebitis. The pancreas is the most commonly involved organ, but several other organ systems are involved, and this helps in clinical suspicion of the diagnosis. A biopsy from any easily accessible site that shows the characteristic histological features is sufficient for diagnosis. Patients respond quickly to steroids, but recurrence is frequent. CONCLUSION: IgG4 related disease is a rare cause of pancreatic tumorous lesions that need a high index of suspicion for diagnosis and should be differentiated from pancreatic neoplastic lesions.

Chronic Myeloid Leukemia with cryptic Philadelphia translocation and extramedullary B-lymphoid blast phase as an initial presentation.

Chronic Myeloid Leukemia (CML) is a clonal myeloproliferative neoplasm (MPN) characterized by the presence of a reciprocal translocation between the long arms of chromosomes 9 and 22, t(9;22)(q34:q11), resulting in fusion of the break point cluster region (BCR) with the ABL gene, which forms an oncogene, the transcript of which is an oncoprotein with a tyrosine kinase function. In the great majority of CML; BCR/ABL1 is cytogenetically visualized as t(9;22); giving rise to the Ph chromosome, harboring the chimeric gene. Cryptic or masked translocations occur in 2-10% patients with no evidence for the BCR/ABL rearrangement by conventional cytogenetics but are positive by Fluorescence in Situ Hybridization (FISH) and/or reverse transcriptase polymerase chain reaction (RT-PCR). These patients are described as Philadelphia negative (Ph negative) BCR/ABL1- positive CML with the chimeric gene present on the derivative chromosome 22, as in most CML cases, or alternatively on the derivative 9 in rare occasions. In the majority of cases, CML is diagnosed in the chronic phase; it is less frequently diagnosed in accelerated crises, and occasionally, its initial presentation is as acute leukemia. The prevalence of extramedullary blast phase (BP) has been reported to be 7-17% in patients with BP. Surprisingly, no extra-medullary blast crises of B- lymphoid lineage have been reported before among cases of CML as the initial presentation. We report an adult male diagnosed as CML- chronic phase when he was shortly presented with treatment-naive extramedullary B-lymphoid blast crises involving multiple lymph nodes, with no features of acceleration or blast crises in the peripheral blood (PB) and bone marrow (BM). In addition the patient had variant/cryptic Philadelphia translocation. This is the first report of CML, on the best of our knowledge, with extramedullary B-lymphoid blast phase, as initial presentation, that showed a cryptic Ph translocation.

Concomitant Classic Hodgkin Lymphoma of Lymph Node and cMYC-Positive Burkitt Leukemia/Lymphoma of the Bone Marrow Presented Concurrently at the Time of Presentation: A Rare Combination of Discordant Lymphomas.

Discordant lymphoma is rare condition in which different types of malignant lymphomas occurring in different anatomic sites. The two diseases may present clinically as concurrent or sequential disease (10). Herein we are reporting a Pakistani female in her 60s, a carrier of hepatitis B virus with multiple comorbidities presented with cervical lymphadenopathy, diagnosed as Hodgkin's lymphoma, mixed cellularity. During the staging workup, the patient was discovered to have extensive bone marrow (BM) involvement by Burkitt leukaemia/lymphoma (BL). Cytogenetic analysis revealed positivity for t(8;14)(q24;q32) confirmed by Fluorescence In Situ Hybridization (FISH) for IGH/MYC. Epstein-Barr virus (EBV) was demonstrated heavily in our case, with (EBV) DNA of 24,295,560 copies/ml by PCR at time of presentation, in addition, the neoplastic cells in both diagnostic tissues (cervical lymph node and BM) demonstrated positivity for EBV. A diagnosis of concomitant EBV related discordant lymphoma (classical Hodgkin lymphoma (cHL) and Burkitt lymphoma (BL) in leukemic phase was made. Among all reported cases, this case is highly exceptional because it is the first case of discordant/composite lymphoma, with this combination and concomitant presentation. Since we are dealing with a case with an exceptionally rare combination, we found it significant to elaborate more on its clinical features, contributing factors including EBV role, response to treatment, complications, and prognosis.

Choriocarcinoma syndrome: a case report and a literature review.

A 35-year-old Qatari man presented to our hospital with a 4-month history of mild abdominal pain, weight loss, and jaundice. He was found to have central intra-abdominal mass and a single testis in the scrotum. His investigations showed cholestatic jaundice and very high level of ß -HCG (1131379 IU/L). CT scans of the chest and abdomen showed a huge pelvic-abdominal mass with extensive retroperitoneal lymphadenopathy, in addition to liver and lung metastases. CT-guided Tru-Cut biopsy of the mass showed mixed germ cell tumor. Chemotherapy was refused by the patient and his family. In the following days, the patient bled from his liver metastases leading to hemorrhagic shock, hemorrhage from metastatic sites of choriocarcinoma containing tumors is named choriocarcinoma syndrome. He was transferred to the medical intensive care unit, where he was intubated and resuscitated. Embolization of the right hepatic artery was done, but failed to control the bleeding, which continued with development of disseminated intravascular coagulopathy and a severe abdominal compartment syndrome, and eventually the patient died.

Quantitative assessment of nuclear grooves in fine needle aspirates of the thyroid: a retrospective cytohistologic study of 94 cases.

OBJECTIVE: To quantify the association between the percentage of nuclear grooves and papillary thyroid carcinoma (PTC) in fine needle aspirates (FNAs) of the thyroid. STUDY DESIGN: All the thyroid FNA cases (n = 1,775) received at the McGill University Health Center Cytopathology Laboratory in 2003 and 2004 were retrieved. The 94 diagnostic FNAs with histologic followup were selected. The percentage of nuclear grooves was quantified manually by counting the number of grooves in 300 cells, at x400, in the areas where the nuclear grooves were most frequent. Using descriptive statistics and graphs, we evaluated the association between the percentage of nuclear grooving and 2 outcomes of surgical diagnosis. RESULTS: The mean percentage of nuclear grooves was 23.7% in PTC vs. 9.44% in non-PTC cases. We identified the cut-off of 20% nuclear grooving as having the optimal positive predictive value of 80% for presence of PTC and negative predictive value of 77% for absence of PTC. CONCLUSION: The presence of nuclear grooves in > or = 20% of cells, as counted in selective fields where grooves are the most frequent, is highly predictive of PTC.

Accuracy of fine-needle aspiration cytology of axillary lymph nodes in breast cancer patients: a study of 115 cases with cytologic-histologic correlation.

BACKGROUND: Fine-needle aspiration (FNA) cytology of axillary lymph nodes is a simple, minimally invasive technique that can be used to improve preoperative determination of the status of the axillary lymph nodes in patients with breast cancer, thereby serving as a tool with which to triage patients for sentinel versus full lymph node dissection procedures. The aim of the current study was to determine the sensitivity and specificity of FNA cytology to detect metastatic breast carcinoma in axillary lymph nodes. METHODS: A total of 115 FNAs of axillary lymph nodes of breast cancer patients with histologic follow-up (subsequent sentinel or full lymph node dissection) were included in the current study. The specificity and sensitivity, as well as the positive and negative predictive values, were calculated. RESULTS: The positive and negative predictive values of FNA cytology of axillary lymph nodes for metastatic breast carcinoma were 1.00 and 0.60, respectively. The overall sensitivity of axillary lymph node FNA in all the cases studied was 65% and the specificity was 100%. The sensitivity of FNA was lower in the sentinel lymph node group than in the full lymph node dissection group (16% vs 88%, respectively), which was believed to be attributable to the small size of the metastatic foci in the sentinel lymph node group (median, 0.25 cm). All false-negative FNAs, with the exception of 1 case, were believed to be the result of sampling error. There was no 'true' false-positive FNA case in the current study. CONCLUSIONS: FNA of axillary lymph nodes is a sensitive and very specific method with which to detect metastasis in breast cancer patients. Because of its excellent positive predictive value, full axillary lymph node dissection can be planned safely instead of a sentinel lymph node dissection when a preoperative positive FNA result is rendered. .