Rashpal Flora

Sporadic medullary thyroid carcinoma with a pedunculated intraluminal internal jugular vein recurrence: A case report and literature review

Medullary thyroid carcinoma (MTC) is an uncommon usually slowly progressing neuroendocrine tumour that arises from calcitonin (CT) producing parafollicular C cells of the thyroid gland. It accounts for approximately 5% of all thyroid cancers. The majority of MTCs are sporadic (75%) whilst 25% are part of the MEN 2 hereditary syndrome (MEN 2A and MEN 2B and familial MTC). Mutations of the proto-oncogene, RET (Rearranged during Transfection), found on chromosome 10q11, are present in more than 95% of hereditary MTCs and about 25% of sporadic MTCs. MTC metastasizes primarily via lymphatic spread, to central, and lateral nodal neck compartments and the anterior and superior mediastinum. Distant haematogenous spread targets the lungs, liver, bone and brain, and is presumed to be secondary to a lymphatic pathway. There are no previously documented reports of a focal pedunculated metastases located within the jugular vein. We present the first reported case of a metastatic MTC lesion found in the right internal jugular vein in a man with recurrent MTC.

Surgical Management of Patients with Neuroendocrine Neoplasms of the Appendix: Appendectomy or More?

Background: Appendiceal neuroendocrine neoplasms (ANEN) are mostly indolent tumours treated effectively with simple appendectomy. However, controversy exists regarding the necessity of oncologic right hemicolectomy (RH) in patients with histologic features suggestive of more aggressive disease. We assess the effects of current guidelines in selecting the surgical strategy (appendectomy or RH) for the management of ANEN. Methods/Aims: This is a retrospective review of all ANEN cases treated over a 14-year period at 3 referral centres and their management according to consensus guidelines of the European and the North American Neuroendocrine Tumor Societies (ENETS and NANETS, respectively). The operation performed, the tumour stage and grade, the extent of residual disease, and the follow-up outcomes were evaluated. Results: Of 14,850 patients who had appendectomies, 215 (1.45%) had histologically confirmed ANEN. Four patients had synchronous non-ANEN malignancies. One hundred and ninety-three patients had index appendectomy. Seventeen patients (7.9%) had lymph node metastases within the mesoappendix. Forty-nine patients underwent RH after appendectomy. The percentages of 30-day morbidity and mortality after RH were 2 and 0%, respectively. Twelve patients (24.5%) receiving completion RH were found to have lymph node metastases. Two patients had liver metastases, both of them synchronous. The median follow-up was 38.5 months (range 1-143). No patient developed disease recurrence. Five- and 10-year overall survival for all patients with ANEN as the only malignancy was both 99.05%. Conclusions: The current guidelines appear effective in identifying ANEN patients at risk of harbouring nodal disease, but they question the oncological relevance of ANEN lymph node metastases. RH might present an overtreatment for a number of patients with ANEN.

Correlation of multiparameter flow cytometry and bone marrow trephine immunohistochemistry in the identification and characterization of neoplastic plasma cells.

Identification and quantification of neoplastic plasma cells (PC) and differentiating them from normal/reactive PC is critical for the work-up, diagnosis and classification of suspected PC neoplasms. Identification of light chain restriction and/or aberrant phenotype using either multiparameter flow cytometry (MFC) or bone marrow trephine biopsy (BMTB) immunohistochemistry (IHC) is needed as a surrogate for PC clonality. There are a few studies in the literature comparing MFC on bone marrow aspirate (BMA) and BMTB in patients with PC disorders (Paiva et al, 2009; Johnsen et al, 2010); yet no comparison between immunophenotypic results obtained through MFC and BMTB-IHC has been undertaken on a larger scale. We aimed to compare these two techniques in their ability to quantify PC, and to demonstrate light chain restriction and an aberrant phenotype. We retrospectively identified 89 presentation samples from PC myeloma (PCM) patients from our archive for which both BMTB-IHC and MFC results were available. PC quantification on BMTB was based on CD138 (clone MI15, Dako, Glostrup, Denmark) immunostain. BMTB were also immunostained for CD3 (clone LN10; Dako), CD20 (clone L26; Dako), CD79a (clone JCB117; Dako), CD56 (clone 1B6; Leica, Nussloch, Germany), cyclin D1 (CCND1; clone SP4, Thermoshandon, Billerica, MA, USA) and CD117 (Dako, polyclonal) expression. Light chain analysis was performed by IHC (Dako, polyclonal) in all cases and additionally by mRNA in situ hybridization (ISH) (Leica) in 13 cases. The criteria for a diagnosis of PC neoplasm by BMTB-IHC were the presence of PC with abnormal morphology, light chain restriction and/or aberrant PC phenotype. MFC was carried out on BMA samples using a 3-laser, 8-colour BD FACSCANTO II (Becton Dickinson BD, Franklin Lakes, NJ, USA) with the following fluorochrome-antibody combination: FITC-CD38 (clone HB7, BD), PE/CD56 (clone MY31, BD), PerCP-Cy5.5-CD138 (clone MI15; Dako), PE-cy7-CD19 (clone SJ25C1, BD), APC-CyKappa (Dako, polyclonal), APCH7-CyLambda (clone 1-155-2, BD), V450-CD20 (clone L27, BD), V500-CD45 (clone H30, BD). Data interpretation was performed using FACS Diva software (BD) and/or Infinicyt (Cytognos, Salamanca, Spain). Gating and analysis strategies used in this study have been previously described (Rawstron et al, 2008). The MFC criteria for involvement by neoplastic PCs were the presence of PCs (minimum 100 events) with cytoplasmic light chain restriction and/or abnormal PC phenotype. Data was analysed using Microsoft Excel 2010 (Microsoft, Redmond, WA, USA). Statistical analysis was performed using IBM SPSS version 22 (IBM, Armonk, NY, USA). The percentage of PCs (PC%) among all nucleated cells on BMTB-IHC was significantly higher than that by MFC (median 50% vs. 6%; P < 0 001; Table I). There was a positive correlation between the PC% by BMTB-IHC and MFC (Spearman correlation coefficient of R = 0 443, P < 0 001)

Anaplastic Spindle Cell Squamous Carcinoma Arising from Tall Cell Variant Papillary Carcinoma of the Thyroid Gland: A Case Report and Review of the Literature

Tall cell variant (TCV) of papillary thyroid carcinoma (PTC), an aggressive form of thyroid cancer, is characterised by 50% of cells with height that is three times greater than the width. Very rarely, some of these cancers can progress to spindle cell squamous carcinoma (SCSC) resulting in cancers with elements of both SCSC and TCV PTC. Here we report a case of SCSC arising from TCV PTC. In addition to this case, we have performed a literature review and compiled all published reports of SCSC arising from TCV PTC, including the nature of treatment and the prognosis for each of the 20 patients recorded. This is intended for use as a guide for clinicians in what the most appropriate treatment options may be for a newly diagnosed patient. Due to the rarity coupled with diagnosis occurring at a very advanced stage of disease progression, performing clinical trials is difficult and therefore drawing conclusions on optimal treatment methods remains a challenge.

Diagnostic Utility of Lymphoid Enhancer Binding Factor 1 Immunohistochemistry in Small B-Cell Lymphomas

Objectives Recent studies have shown that lymphoid enhancer binding factor 1 (LEF1) is a useful marker for chronic lymphocytic B-cell leukemia (CLL)/small lymphocytic lymphoma. Yet, it is not still being widely used in a diagnostic setting. In this study, we document the experience with LEF1 immunohistochemistry during routine diagnostics. Methods In total, 191 B-cell lymphoma cases from Hammersmith Hospital, Imperial College NHS Healthcare Trust (London, UK) were investigated by immunohistochemistry for LEF1 during routine diagnostic workup. These cases included both bone marrow trephines and lymph node biopsy specimens. The monoclonal antibody clone EPR2029Y was used. Results LEF1 expression was strong and diffuse (>70% of cells) in most cases. Few CLL cases showed a staining in proliferation centers only. Seventy-seven of 80 CLL cases expressed LEF1. Other entities expressing LEF1 included one of 38 follicular lymphomas, two of 33 marginal zone lymphomas, and one diffuse large B-cell lymphoma with a background of follicular lymphoma grade 3B. Sensitivity for LEF1 for the diagnosis of CLL was 0.96, and specificity was 0.93. Conclusions In this study, we could demonstrate the diagnostic utility of LEF1. LEF1 is a sensitive and specific marker for CLL and is helpful in the diagnosis of diagnostically challenging small B-cell lymphomas.

1158PROLE OF MICRORNA AS BIOMARKERS IN SMALL BOWEL NEUROENDOCRINE TUMOURS

ABSTRACT Aim: Novel molecular biomarkers are needed in neuroendocrine tumours (NET) which can better stratify patients based on factors such as disease aggressiveness and treatment response. Our study was performed on small bowel neuroendocrine tumours (SBNET). Aim 1: determine the global microRNA (miRNA) profile of SBNET. Aim 2: identify miRNA involved in tumour progression for use used as potential biomarkers. Methods: Forty four samples were studied with matched primary/metastasis/normal formalin fixed paraffin embedded tissue from 15 SBNET patients. Included were primary SBNET (n = 15), lymph node metastases (n = 9), adjacent normal small bowel (n = 13) and normal lymph nodes (n = 7). RNA was extracted and 800 miRNA quantified using nCounter® technology (NanoString Technologies, Seattle, USA). Normalisation was performed using the geometric mean of the 100 highest expressed miRNA followed by quantile normalisation. Two-sample t test (p value Results: Out of 800 miRNA, 178 were significantly up or downregulated in SBNET compared to adjacent non-neoplastic tissue. The most up regulated miRNA (-204-5p, -7-5p, -375) and the most downregulated miRNA (-215, -451a -378a-3p, -378i) were chosen for future validation as biomarkers of progression. There were 3 miRNA (-1, -1233, 143-3p) significantly downregulated in lymph node metastasis compared to the primary. One miRNA (-2117) was significantly downregulated in lymph node metastasis compared to normal lymph nodes. Conclusions: These preliminary results provide information on the global miRNA profile of SBNET and show that some miRNA are differentially regulated during tumour progression. Following further validation, these miRNA have the potential to act as biomarkers for patient stratification based on disease aggressiveness, which could inform patient treatment. Disclosure: All authors have declared no conflicts of interest.

Bone marrow trephine biopsy findings in essential thrombocythemia

A woman in her mid-30s presented with unexplained mild splenomegaly (17 cm in greatest dimension by ultrasound scan). Her hemoglobin was 13.8 g/L. Her platelet count was initially 586 3 10/L and remained relatively steady over the following 7 years ranging between 416 and 586 3 10/L. Her white cell count and neutrophil count was only minimally increased on intermittent occasions during these years.