Nadia Talat

Castleman's Disease: Systematic Analysis of 416 Patients from the Literature

BACKGROUND Castlemans disease is a rare primary disease of the lymph nodes with limited available clinical information. METHODS A systematic literature search identified 416 cases amenable to detailed analysis. RESULTS In HIV(-) patients, centricity, pathology type, the presence of symptoms, gender, and age all predict outcome in univariate analyses. The 3-year disease-free survival (DFS) rate for patients with unicentric hyaline vascular disease (49.5% of cases, class I) was 92.5%, versus 45.7% for those with multicentric plasma cell disease (20.2% of cases, class III) and 78.0% for those with any other combination (22.6% of cases, class II) (p < .0001). HIV(+) patients (class IV) exclusively presented with multicentric plasma cell disease and had a 3-year DFS rate of only 27.8%. Kaposis sarcoma and lymphoma were observed in 59.3% and 9.4% of HIV(+) patients and in 2.6% and 3.6% of HIV(-) patients (p < .0001). Paraneoplastic pemphigus and the syndrome of polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes were observed exclusively in HIV(-) patients at a rate of 1.3% and 1.8%, respectively. CONCLUSION Clinical, pathological, and viral markers allow for the classification of Castlemans disease into groups with markedly different outcomes and disease associations.

Castleman's disease—a two compartment model of HHV8 infection

Castlemans disease is a primary infectious disease of the lymph node that causes local symptoms or a systemic inflammatory syndrome. Histopathology reveals a destroyed lymph node architecture that can range from hyaline-vascular disease to plasma-cell disease. Viral interleukin 6 (vIL-6) produced during the replication of human herpesvirus type 8 (HHV8) is the key driver of systemic inflammation and cellular proliferation. Stage progression of Castlemans disease results from switches between viral latency and lytic replication, and lymphatic and hematogenous spread. Multicentric plasma-cell disease in HIV-1 patients is associated with HHV8 infection. Polyclonal plasmablast proliferation escapes control in the germinal center with eventual malignant transformation into non-Hodgkin lymphoma. Surgery produces excellent results in unicentric disease, while multicentric disease responds to anti-CD20 therapy or IL-6 and chemotherapy. Lymphovascular endothelium and naive B cells are infectious reservoir-opening options for antiangiogenic and anti-CD19 strategies to enhance outcomes in patients with systemic disease.

Lymph Node Involvement and Surgical Approach in Parathyroid Cancer

BackgroundThe best surgical approach to parathyroid cancer is disputed. Recommendations vary and are built on incoherent evidence. High rates of recurrence and death require an in-depth review of underlying findings.MethodsThis retrospective study includes 11 patients with parathyroid cancer who underwent surgery with central and/or lateral neck dissection by a single surgeon between 2005 and 2010. The diagnosis was based on histopathological criteria in all patients. Patterns of lymph node and soft tissue involvement of these and formerly reported patients were analysed based on full-text review of all published cases of parathyroid cancer.ResultsIn this series only 1 of 11 patients (9.1%) manifested lymph node metastasis. In the literature, lymph node metastases have been reported in only 6.5% of 972 published patients, or in 32.1% of the 196 in whom lymph node involvement was assessed by the authors. They were, with few exceptions, localised in the central compartment. Recurrence in soft tissue is more frequent than in locoregional lymph nodes.ConclusionOncological en bloc clearance of the central compartment with meticulous removal of all possibly involved soft tissues, including a systematic central lymph node resection, may improve outcomes and should be included in the routine approach to the suspicious parathyroid lesion. There is no need for a prophylactic lateral neck dissection.

The Clinical Spectrum of Multiple Endocrine Neoplasia Type 2a Caused by the Rare Intracellular RET Mutation S891A

BACKGROUND Germline missense mutations of the RET protooncogene cause a clinical spectrum called multiple endocrine neoplasia (MEN) type 2. A strong genotype-phenotype correlation results in major implications for the clinical approach. More information on less common mutations is needed to advance specific guidance. PATIENTS AND METHODS We report individualized patient information on 36 carriers of the intracellular RET gene mutation S891A from three centers and clustered data of 38 former patients reported in the literature in nine additional studies. RESULTS S891A mutation accounts for up to 5% of all patients to date reported with RET mutations and 16% of those hitherto reported with intracellular mutations. S891A mutation caused medullary thyroid cancer (MTC) in 69.4%, pheochromocytoma in 2.8%, and parathyroid hyperplasia in 8.3% of the 36 patients of this case series and in 63.5, 4.1, and 4.1%, respectively, for the entire groups of 74 patients. The youngest age of onset for MTC in this group was 17 yr (median, 46 yr; range, 17-80 yr), for pheochromocytoma 46 yr (median, 46 yr), and for parathyroid hyperplasia 17 yr (median, 20 yr, range, 17-46 yr). Persistence of MTC was described in 14.3% of patients with available follow-up. Additional findings included corneal nerve thickening in three of 74 patients (4.1%). CONCLUSION This intracellular mutation can initiate the full spectrum of MEN2a, initiates MTC at an early age, and causes recurrence and death if undertreated. We recommend stringent adherence to established guidance in MEN2a in this rare mutation.

Inflammatory diseases of the parathyroid gland

Talat N, Diaz‐Cano S & Schulte K‐M
(2011) Histopathology59, 897–908
Inflammatory diseases of the parathyroid gland

18F-FDG PET rarely provides additional information to 11C-methionine PET imaging in hyperparathyroidism

Aim The aim of this study was to assess the utility of combined 11C-methionine and 18F-FDG PET/CT imaging in hyperparathyroidism. Patients and Methods We reviewed all scans performed for hyperparathyroidism with both 11C-methionine and 18F-FDG PET/CT or PET in our institution since 1993. Forty-three patients (47 pairs of scans) were included (13 men and 30 women) with a mean age of 63 years. 11C-methionine and 18F-FDG PET/CT scans were classified as positive or negative for localization of abnormal parathyroid tissue, and the site of uptake was noted in the positive scans. Other concurrent imaging (99mTc-MIBI scintigraphy, ultrasonography, CT, or MRI) findings were also noted when performed. Clinical follow-up information was available in 27 patients (30 episodes). Results Of the 47 PET scan episodes, 23 (49%) were positive. Twenty-two 11C-methionine scans showed abnormal focal localization of which 10 also showed concordant abnormal 18F-FDG uptake. One patient was positive with 18F-FDG and negative with 11C-methionine. Of the 16 patients who underwent subsequent surgery, 6 had concordant 11C-methionine, 18F-FDG, and surgical findings; 6 had concordant 11C-methionine and surgical findings; 1 had concordant 18F-FDG and surgical findings; and 3 had both PET scans negative but had adenomas excised during surgery. Of the 3 with both PET scans negative and discordant surgical findings, 1 had mediastinal parathyroid lipoadenoma excised and 2 had normally sited parathyroid adenoma excised. Conclusions 18F-FDG PET/CT rarely provides additional information and could be saved for patients in whom 11C-methionine PET/CT is negative.

Retroperitoneal unicentric Castleman's disease with multiple lymph node involvement.

A 78-year-old woman with B-symptoms was referred for a left adrenal incidentaloma of 5 cm. Imaging revealed features compatible with adrenal cancer. The authors excluded excess production of catecholamines or adrenal steroids. The tumour was removed by en bloc radical left retroperitonectomy with adrenalectomy, nephrectomy, interaortocaval lymphadenectomy and splenectomy. Histology demonstrated periadrenal hyaline vascular Castleman’s disease with local infiltration and 14 positive lymph nodes. The lymphoid infiltrate spilled into the adjacent renal cortex. HHV8 was negative. The Ki67 proliferative index was 30–40% in germinal centres. There was no syn- or metachronous disease on extended imaging including fluorodeoxyglucose positron emission tomography-CT and narrow follow-up at 3 years. This is a rare case of unicentric hyaline vascular Castleman’s disease with documented locoregional lymph node involvement. The case exemplifies the transition from unifocal unicentric disease into disseminated disease with involvement of multiple lymph node stations (multicentric disease). The authors demonstrate surgical cure by oncological resection.