Rana S. Hoda

A Panel of Four miRNAs Accurately Differentiates Malignant from Benign Indeterminate Thyroid Lesions on Fine Needle Aspiration

Purpose: Indeterminate thyroid lesions on fine needle aspiration (FNA) harbor malignancy in about 25% of cases. Hemi- or total thyroidectomy has, therefore, been routinely advocated for definitive diagnosis. In this study, we analyzed miRNA expression in indeterminate FNA samples and determined its prognostic effects on final pathologic diagnosis. Experimental Design: A predictive model was derived using 29 ex vivo indeterminate thyroid lesions on FNA to differentiate malignant from benign tumors at a tertiary referral center and validated on an independent set of 72 prospectively collected in vivo FNA samples. Expression levels of miR-222, miR-328, miR-197, miR-21, miR-181a, and miR-146b were determined using reverse transcriptase PCR. A statistical model was developed using the support vector machine (SVM) approach. Results: A SVM model with four miRNAs (miR-222, miR-328, miR-197, and miR-21) was initially estimated to have 86% predictive accuracy using cross-validation. When applied to the 72 independent in vivo validation samples, performance was actually better than predicted with a sensitivity of 100% and specificity of 86%, for a predictive accuracy of 90% in differentiating malignant from benign indeterminate lesions. When Hurthle cell lesions were excluded, overall accuracy improved to 97% with 100% sensitivity and 95% specificity. Conclusions: This study shows that that the expression of miR-222, miR-328, miR-197, and miR-21 combined in a predictive model is accurate at differentiating malignant from benign indeterminate thyroid lesions on FNA. These findings suggest that FNA miRNA analysis could be a useful adjunct in the management algorithm of patients with thyroid nodules. Clin Cancer Res; 18(7); 2032–8. ©2012 AACR.

The emerging technique of electromagnetic navigation bronchoscopy-guided fine-needle aspiration of peripheral lung lesions: Promising results in 50 lesions

Literature on the diagnostic yield of electromagnetic navigation bronchoscopy (ENB) with ENB‐guided fine‐needle aspiration (ENB‐FNA) in peripheral lung lesions (PLLs) that measure ≤u20092 cm is scarce. Data on the diagnostic yield of ENB‐FNA for PLLs when performed in conjunction with positron emission tomography‐computed tomography (PET‐CT), rapid on‐site evaluation (ROSE), ENB‐guided bronchial brushing (ENB‐BB), and ENB‐guided transbronchial biopsy (ENB‐TBx) is also limited. In this study, the authors evaluated their experience with ENB‐FNA performed in conjunction with all 4 modalities: PET‐CT, ROSE, ENB‐BB, and ENB‐TBx.

Diagnostic utility of the monoclonal antibody A103 in fine-needle aspiration biopsies of the adrenal.

Fine-needle aspiration (FNA) of the adrenal is a useful modality for the evaluation of primary and metastatic neoplasms. Until now, however, few reliable markers existed for the positive identification of adrenal cortical cells. Originally studied as a melanoma marker, Melan-A, as detected by the murine monoclonal antibody, A103, has gained recent attention as a marker for steroid-producing cells. Formalin-fixed, paraffin-embedded cell blocks from 24 adrenal FNA specimens were stained for cytokeratins (AE1/AE3) and Melan-A (A103). Seven of 8 cases containing normal, hyperplastic, and neoplastic adrenal cortical cells were positive for A103. Among 16 cases of metastatic carcinoma, tumor cells in 14 samples were positive for cytokeratins but negative for A103. The A103 monoclonal antibody is a sensitive marker for the identification of normal, hyperplastic, and neoplastic adrenal cortical cells in cell blocks of adrenal FNA specimens. With the exception of melanoma, A103 reactivity is restricted to adrenal cortical and other steroid-producing cells. A103 should be used routinely for the evaluation of FNA specimens of adrenal mass lesions.

Transformation of Follicular Lymphoma to Plasmablastic Lymphoma With c-myc Gene Rearrangement

Follicular lymphoma (FL) is an indolent lymphoma that transforms to high-grade lymphoma, mostly diffuse large B-cell lymphoma, in about a third of patients. We present the first report of a case of FL that transformed to plasmablastic lymphoma (PBL). Clonal transformation of the FL to PBL was evidenced by identical IGH/BCL2 gene rearrangements and VDJ gene usage in rearranged IGH genes. IGH/ BCL2 translocation was retained in the PBL, which also acquired c-myc gene rearrangement. Genealogic analysis based on somatic hypermutation of the rearranged IGH genes of both FL and PBL suggests that transformation of the FL to PBL occurred most likely by divergent evolution from a common progenitor cell rather than direct evolution from the FL clone. Our study of this unusual case expands the histologic spectrum of FL transformation and increases our understanding of the pathogenetic mechanisms of transformation of indolent lymphomas to aggressive lymphomas.

Intercellular Adhesion Molecule-1 (ICAM-1) is Upregulated in Aggressive Papillary Thyroid Carcinoma

BackgroundIntercellular adhesion molecule-1 (ICAM-1) is implicated in carcinogenesis. In this study we examined the expression of ICAM-1 in papillary thyroid cancer (PTC). We hypothesized that ICAM-1 correlates with indicators of tumor aggressiveness in PTC.MethodsThirty-five primary and metastatic PTCs, five follicular adenomas, five Hashimoto thyroiditis, five nodular hyperplasia, and eight normal thyroid tissue samples were analyzed for ICAM-1 gene expression using quantitative reverse-transcription polymerase chain reaction (RT-PCR). ICAM-1 gene expression was analyzed at protein level by immunohistochemistry (IHC) using a semiquantitative score. Gene expression and intensity levels were correlated with markers of tumor aggressiveness including BRAF V600E mutation, tumor size, extrathyroidal extension (ETE), angiolymphatic invasion, and lymph node metastasis.ResultsICAM-1 gene expression was higher in PTC (pxa0=xa00.01) and lymph node metastases (pxa0=xa00.03) when compared with benign tumors and Hashimoto’s. Furthermore, PTCs exhibiting BRAF V600E mutation (pxa0=xa00.01), ETE (pxa0<xa00.01), and lymph node metastasis (pxa0=xa00.02) were associated with higher ICAM-1 levels. Gene expression correlated with protein levels on IHC. Additionally, poorly differentiated thyroid carcinoma had a higher ICAM-1 intensity score compared with well-differentiated carcinoma (pxa0=xa00.03).ConclusionsICAM-1 expression is upregulated in papillary thyroid carcinoma. Furthermore, ICAM-1 upregulation correlated with aggressive tumor features such as BRAF V600E mutation, ETE, and lymph node metastasis, suggesting that ICAM-1 plays a role in thyroid cancer progression.

Are microinvasion and micrometastasis in breast cancer mountains or molehills

BACKGROUNDnThe increased rate of early detection of breast cancer due to widespread mammographic screening has led to an increased incidence of in situ as well as microinvasive carcinoma. The enhanced pathological examination to which sentinel lymph nodes are subjected has led to an increased rate of detection of micrometastatic carcinoma. Despite the augmented rate of diagnoses of both diseases, the pathological diagnoses as well as clinical management of these entities continue to be controversial.nnnDATA SOURCESnA computerized literature search was performed on the Medline and PubMed database from 1990 to date. Relevant earlier publications were also perused. The database of the Department of Pathology at New York Presbyterian Hospital-Well Medical College of Cornell University were also accessed.nnnCONCLUSIONSnBased on cumulative data, patients diagnosed with either microinvasive or micrometastatic carcinoma of breast have a relatively favorable, albeit guarded, prognosis. Treatment recommendations for both of these disease entities continue to be controversial, and may remain so until additional refined clinicopathological data becomes available.

Cytologic diagnosis of metastatic basal cell carcinoma. Report of a case with immunocytochemical and molecular pathologic considerations.

BACKGROUNDnMetastases of basal cell carcinoma (BCC) are extraordinarily rare events, with only about 200 published reports. The usefulness of immunohistochemical markers in the diagnosis of metastatic BCC was previously established on cytologic material. Furthermore, in recent years, numerous molecular markers have been studied to explain its pathogenesis and relatively indolent behavior.nnnCASE REPORTnA 62-year-old, white male presented with lymphadenopathy in the right side of the neck. The patient had a long-standing history of multiple excisions of BCCs during the previous 30 years. Fine needle aspiration biopsy revealed tight clusters and sheets of small, round tumor cells with hyperchromatic nuclei, small nucleoli and minimal cytoplasm. In addition, in some of the clusters the tumor cells showed peripheral palisading. Based on the cytomorphology and diffuse immunohistochemical positivity for a low-molecular-weight cytokeratin marker, MNF 116, and negativity for AE1/AE3, Cam5.2, synaptophysin and chromogranin, a diagnosis of metastatic BCC was rendered. Subsequent histopathologic examination of metastatically involved lymph nodes removed in a radical neck dissection confirmed this diagnosis. In addition, on histologic sections the metastatic tumor cells were found to express bcl-2 and CD44, markers that have been recently studied in cutaneous tumors.nnnCONCLUSIONnIn acquiring metastatic potential, this lesion did not lose the molecular characteristics of bcl-2 and CD44 expression, the two features deemed to be important in the indolent behavior of BCC.

Metastatic squamous-cell carcinoma in pericardial effusion : Report of four cases, two with cardiac tamponade

For reasons unknown, metastatic squamous‐cell carcinoma is a rare cause of pleural effusions and is even less common in pericardial effusions. A review of all pericardial effusions examined in the Cytology Service at Montefiore Medical Center over a 15‐year (1980–1994) period was undertaken (N = 251). Four cases with metastatic squamous‐cell carcinoma were identified among 39 malignant effusions. Two patients with metastatic squamous‐cell carcinoma presented with cardiac tamponade, and the other two cases had progressive cardiac failure. The diagnostic cells on cytology evaluation were scant in all four cases but exhibited classical features of metastatic squamous carcinoma, such as cytoplasmic keratinization, intercellular bridges, and occasional “pearl” formation. Pericardial biopsies available in three patients, two with cardiac failure and one with cardiac tamponade, were negative. In all four cases the primary tumor was a bronchogenic carcinoma. Metastatic squamous‐cell carcinoma is an uncommon cause of pericardial effusion and usually indicates the presence of a bronchogenic carcinoma with a rapidly fatal outcome. Cytologic examination of pericardial fluid is essential in the evaluation of such patients. Diagn. Cytopathol. 1998;18:422–424.

Solitary mastocytoma in an infant - case report with review of literature.

Solitary mastocytoma in infants is an uncommon disease which is characterized by mast cell hyperplasia and release of mast cell mediators. The most common presentation is pruritus. The treatment of solitary mastocytoma is symptomatic. Cutaneous mastocytoma tend to resolve by adulthood.

Ultrasound-guided fine-needle aspiration diagnosis of adenocarcinoma of esophagus with signet-ring cell features arising in Barrett's esophagus: A case report

We report a rarely documented case of adenocarcinoma of esophagus with signet‐ring cell features arising in a Barretts esophagus. This was diagnosed by employing combined endosonography and fine‐needle aspiration cytology. The patient had progressive dysphagia and a poorly circumscribed mass involving the distal esophagus and gastroesophageal junction. An incisional biopsy was performed which showed Barretts esophagus with highly atypical glands suspicious for adenocarcinoma. Following that, an ultrasound‐guided endoscopic fine‐needle aspiration revealed a cellular specimen with multiple groups and singly dispersed atypical glandular cells with a predominance of signet‐ring features. These findings represented an adenocarcinoma with signet‐ring cell features arising in Barretts esophagus. Diagn. Cytopathol. 1998;19:51–54.