Hodgkin's lymphoma of the thyroid: a clinicopathologic study of five cases and review of the literature.

Hodgkin's lymphoma rarely involves the thyroid gland. We report the clinical and pathologic features of five cases of Hodgkin's lymphoma that presented as thyroid lesions. All five patients were females, aged 29-59 years. Three patients had a history of chronic thyroiditis and hypothyroidism and two were euthyroid. One patient had a remote history of Hodgkin's lymphoma. Imaging studies showed a 'cold' nodule (three cases) or a diffusely enlarged thyroid gland, resembling goiter or fibrosclerosing thyroiditis (two cases). Thyroid fine-needle aspiration was performed before thyroidectomy in all cases; three of these cases contained some atypical cells, raising the possibility of Hodgkin's lymphoma. Histologically, all cases were classical Hodgkin's lymphoma, nodular sclerosis subtype. The four patients with primary thyroid lymphoma had Stage IIE disease. All patients were treated with surgical excision and chemotherapy, with or without radiation therapy, and were alive after 2 months to 7 years of follow-up. A review of the English literature between 1962 and 2005 revealed 16 cases of thyroid Hodgkin's lymphoma, with a female preponderance and generally favorable outcome similar to the cases in our series. Hodgkin's lymphoma of the thyroid is rare and can mimic a primary thyroid epithelial tumor or thyroiditis clinically. Histologic diagnosis may be difficult due to marked fibrosis. Hodgkin's lymphoma should be considered in the differential diagnosis of thyroid neoplasms.     

Immune reconstitution and associated infections following axicabtagene ciloleucel in relapsed or refractory large B-cell lymphoma

CD19 chimeric antigen receptor T (CAR T)-cell therapy with axicabtagene ciloleucel (axi-cel) for relapsed or refractory (R/R) large B-cell lymphoma (LBCL) may lead to durable remissions, however, prolonged cytopenias and infections may occur. In this single center retrospective study of 85 patients, we characterized immune reconstitution and infections for patients remaining in remission after axi-cel for LBCL. Prolonged cytopenias (those occurring at or after day 30 following infusion) were common with ≥grade 3 neutropenia seen in 21 of 70 (30%) patients at day 30 and persisting in 3 of 31 (9.7%) patients at 1 year. B cells were undetectable in 30 of 34 (88.2%) patients at day 30, but were detected in 11 of 19 (57.9%) at 1 year. Median immunoglobulin G levels levels reached a nadir at day 180. By contrast, CD4 T cells decreased from baseline and were persistently low with a median CD4 count of 155 cells/mL at 1 year after axi-cel (n=19, range: 33– 269). In total, 23 of 85 (27.1%) patients received intravenous immunoglobulins after axi-cel, and 34 of 85 (40%) received granulocyte-colony stimulating factor. Infections in the first 30 days occurred in 31 of 85 (36.5%) patients, of which 11 of 85 (12.9%) required intravenous antibiotics or hospitalization (“severe”) and were associated with cytokine release syndrome, neurotoxicity, tocilizumab use, corticosteroid use, and bridging therapy on univariate analyses. After day 30, seven severe infections occurred, with no late deaths due to infection. Prolonged cytopenias are common following axi-cel therapy for LBCL and typically recover with time. Most patients experience profound and prolonged CD4 T-cell immunosuppression without severe infection.     

Diagnostic utility of cerebrospinal fluid flow cytometry in patients with and without prior hematologic malignancy

Flow cytometry (FCM) is an adjunct study to routine analysis of cerebrospinal fluid (CSF) to investigate for involvement by a hematologic malignancy. However, in our experience, FCM only infrequently detects abnormalities in CSF. To help optimize resources without forfeiting clinically important data, we sought to determine evidence‐based indications and criteria for performing FCM on CSF. FCM results of 316 consecutive CSF specimens were retrospectively reviewed and correlated with clinical history, total nucleated cell (TNC) counts, and results of concurrent cytologic review. Of 255 samples adequate for analysis, 54% were from patients with a prior history of hematologic malignancy, of which 12% (17 cases) were abnormal by FCM. Corresponding TNC counts among samples with abnormal FCM ranged from 0–1050 cells/µL, and only 44% showed abnormal morphology on concurrent cytology. Of the remaining 46% of samples from patients with no known history of hematologic malignancy who had CSF sampling for neurological indications, only one (1%) was abnormal by FCM. This specimen had an elevated TNC count (39 cells/µL) but lacked clearly abnormal findings on concurrent cytology. These results support the use of CSF FCM only in patients with a history of hematologic malignancy or, in the absence of such a history, in samples showing pleocytosis. If these criteria were applied to the current cohort using a TNC count cut‐off of > 5 cells/µL, 23% of samples would have been deferred from testing, resulting in decreased cost, improved efficiency, and reduction in the need for unnecessary testing without a negative impact on clinical care. Am. J. Hematol. 89:978–984, 2014. © 2014 Wiley Periodicals, Inc.     

Elective antireflux surgery in the US: an analysis of national trends in utilization and inpatient outcomes from 2005 to 2010

Background

Previous research suggested that antireflux surgery reached its peak volume in the US more than a decade ago. Factors such as changes in population demographics and improvements in surgical outcomes may have reversed this decline. We sought to examine national trends in the management of antireflux surgery patients and identify patient and hospital characteristics associated with postoperative complications.

Methods

We analyzed data from the Nationwide Inpatient Sample to identify adults with gastroesophageal reflux disease or esophagitis who underwent elective antireflux surgery between 2005 and 2010. Patient and hospital characteristics were analyzed. A multivariate logistic regression model was used to identify characteristics associated with an increased risk of postoperative complications following laparoscopic antireflux surgery.

Results

The volume of elective antireflux surgery remained relatively stable between 2005 (n = 15,819) and 2010 (n = 18,780). The percentage of patients older than 64 years of age increased from 21.1 % in 2005 to 30.9 % in 2010 (p < 0.01), while the percentage with a Charlson score over 2 more than doubled (1.2–2.7 %; p < 0.01). Inpatient complication rates (6.3 vs. 6.6 %; p = 0.21) and mortality (0.08 vs. 0.21; p = 0.72) were unchanged. On multivariate analysis, patients older than 79 years were three times as likely to develop a complication (odds ratio [OR] 3.1; 95 % CI 2.1–4.5) as were patients with a Charlson score over 2 (OR 3.1; 95 % CI 2.2–4.3).

Conclusions

Today’s antireflux surgery patient population is a higher-risk cohort, but complication rates have remained stable and inpatient mortality has declined more than 50 % over the past decade. Given these findings, additional research is needed to understand why antireflux surgery is underutilized, with a decline of more than two-thirds since its peak in 1999.     

No evidence for the need of a routine renal transplant ultrasound after elective transplant ureteric stent removal—A retrospective cohort study

Transplant ureteric stent insertion reduces the incidence of MUCs, but it is not known whether routine PSRGU is needed to detect unmasked MUCs. This study evaluated whether routine PSRGU in the pRTR is a useful tool to identify MUCs before they become clinically apparent. A retrospective analysis was undertaken of the clinical outcomes following elective stent removal from pediatric kidney‐only transplant recipients at two London centers between 2012 and 2016. Our policy was to perform PSRGU either routinely or urgently if there were concerning symptoms or biochemical evidence of renal allograft dysfunction. Elective stent removal was performed in 86% (97 of 113 pRTR), and 75 (77%) of whom had routine PSRGU at a median (IQR) of 6 (2‐8) days after stent removal. There were changes to management in 3 (4%) of pRTR with PSRGU identifying no MUC. Nineteen patients (25%) had urgent PSRGU, most commonly due to renal allograft dysfunction, at a median (IQR) of 5.5 (2.7‐12.3) days after stent removal. Of these, two pRTR required ureteric intervention. For our current practice of removing transplant stents at 4‐6 weeks post‐transplantation, our study has found no evidence to support routine PSRGU after elective stent removal.     

Activin A promotes multiple myeloma-induced osteolysis and is a promising target for myeloma bone disease

Understanding the pathogenesis of cancer-related bone disease is crucial to the discovery of new therapies. Here we identify activin A, a TGF-β family member, as a therapeutically amenable target exploited by multiple myeloma (MM) to alter its microenvironmental niche favoring osteolysis. Increased bone marrow plasma activin A levels were found in MM patients with osteolytic disease. MM cell engagement of marrow stromal cells enhanced activin A secretion via adhesion-mediated JNK activation. Activin A, in turn, inhibited osteoblast differentiation via SMAD2-dependent distal-less homeobox–5 down-regulation. Targeting activin A by a soluble decoy receptor reversed osteoblast inhibition, ameliorated MM bone disease, and inhibited tumor growth in an in vivo humanized MM model, setting the stage for testing in human clinical trials.     

Primary effusion lymphoma

Primary effusion lymphoma (PEL) is a rare HIV-associated non-Hodgkin's lymphoma (NHL) that accounts for approximately 4% of all HIV-associated NHL. PEL has a unique clinical presentation in having a predilection for arising in body cavities such as the pleural space, pericardium, and peritoneum. PEL cells are morphologically variable with a null lymphocyte immunophenotype and evidence of human herpesvirus (HHV)-8 infection. The exact oncogenic mechanisms of HHV-8 have not been clearly defined. Treatment is usually with combination CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy and antiretroviral therapy (if HIV positive). The prognosis for PEL is poor, with a median survival time of around 6 months. As the exact molecular steps in HHV-8-driven oncogenesis are unraveled, it is hoped that more specific therapeutic targets will be revealed.