Zahra Maleki

Application of the hybrid capture 2 assay to squamous cell carcinomas of the head and neck: a convenient liquid-phase approach for the reliable determination of human papillomavirus status.

A growing proportion of head and neck squamous cell carcinoma (HNSCC) is caused by the human papillomavirus (HPV). In light of the unique natural history and prognosis of HPV‐related HNSCCs, routine HPV testing is being incorporated into diagnostic protocols. Accordingly, there is an escalating demand for an optimal detection strategy that is sensitive and specific, transferrable to the diagnostic laboratory, standardized across laboratories, cost‐effective, and amenable to broad application across specimen types including cytologic preparations.

Human papillomavirus status of head and neck cancer as determined in cytologic specimens using the hybrid-capture 2 assay

OBJECTIVE A standardized assay to determine the HPV status of head and neck squamous cell carcinoma (HNSCC) specimens has not yet been established, particularly for cytologic samples. The goal of this study was to determine whether the hybrid capture-2 (HC-2) assay, already widely used for the detection of high risk HPV in cervical brushings, is applicable to cytologic specimens obtained from patients with suspected HNSCCs. MATERIALS AND METHODS Fine needle aspirates (FNA) of cervical lymph nodes were pre-operatively obtained from patients with suspected HNSCCs and evaluated for the presence of HPV using the HC-2 assay. HPV analysis was performed on the corresponding resected tissue specimens using p16 immunohistochemistry (IHC) and HR-HPV in situ hybridization (ISH). A cost analysis was performed using the Center for Medicare & Medicaid Services. RESULTS HPV status of the cervical lymph node metastases was correctly classified using the HC-2 assay in 84% (21/25) of cases. Accuracy was improved to 100% when cytologic evaluation confirmed the presence of cancer cells in the test samples. The estimated cost savings to CMS using the HC-2 assay ranged from

The Fidelity of p16 Staining as a Surrogate Marker of Human Papillomavirus Status in Fine- Needle Aspirates and Core Biopsies of Neck Node Metastases: Implications for HPV Testing Protocols

113.74 to

Utility of the Quantitative Ki-67 Proliferation Index and CD56 Together in the Cytologic Diagnosis of Small Cell Lung Carcinoma and Other Lung Neuroendocrine Tumors

364.63 per patient. CONCLUSIONS HC-2 is a reliable method for determining the HPV status of HNSCCs. Its application to HNSCCs may reduce costs by helping to localize the primary site during the diagnostic work-up as well as decrease the interval time of determining the HPV status which would be relevant for providing prognostic information to the patient as well as determining eligibility for clinical trials targeting this unique patient population.

Hemorrhagic synovial cyst: the possible role of initial trauma and subsequent microtrauma in its pathogenesis: case report.

Objectives: The importance of detecting human papillomavirus (HPV) in head and neck squamous cell carcinoma (HNSCC) has resulted in a growing expectation for HPV testing of clinical samples. Although testing protocols vary, most pertain to primary tumor biopsies/resections. Testing of fine-needle aspirates and core biopsies (FNACBs) is advantageous, but it is unclear whether technical and biological factors adversely affect the fidelity of HPV detection in these samples. Methods: Data was collected for 85 patients with regionally metastatic HNSCC that had undergone FNACB with HPV analysis as part of clinical care. HPV testing consisted of p16 immunostaining and HPV in situ hybridization (ISH). The FNACBs were compared with the subsequent biopsies/resections for HPV status. Results: p16 staining was present in 60 cases (71%). p16 positivity was predictive of oropharyngeal origin (p < 0.001) and correlated with the presence of HPV by ISH (98% correlation). On comparison of the metastases and primary cancers, the HPV status was concordant in 58 of 59 cases (98%). Conclusions: For patients with metastatic HNSCC, p16 staining reliably reflects the HPV status of the primary tumor. p16 staining of FNACBs may obviate the need for more invasive sampling of the primary cancer solely for the purpose of HPV testing.

Periventricular Leukomalacia and Placental Histopathologic Abnormalities

Background: Distinction of small cell lung carcinoma (SCLC) from non-small cell lung carcinoma (NSCLC) is critical because of the differences in prognosis and management. Patients with SCLC usually present with distant metastasis, and clinicians demand an accurate diagnosis in order to initiate appropriate therapy. Limited cytology material, occasionally with crush artifact, is not uncommon. Therefore, robust cytomorphologic features and a small immunostaining panel would be ideal to differentiate SCLC from NSCLC and other neuroendocrine neoplasms. We evaluated CD56 and the quantitative Ki-67 immunohistochemical panel in comparison to synaptophysin and chromogranin, along with cytomorphology to diagnose SCLC. Design: Eighty-eight cases of SCLC were retrieved from the cytology archives of The Johns Hopkins Hospital. Forty neuroendocrine neoplasms were used as control cases. Results: SCLCs included 33 lung cases and 55 metastatic lesions. The specimens were obtained by fine needle aspiration, thoracocentesis, bronchoalveolar lavage and abdominal paracentesis. CD56 was expressed in 98.9% of SCLCs, which is significantly more sensitive than synaptophysin and chromogranin. The Ki-67 labeling index was high (>70%) in all cases, which is a reliable marker to differentiate SCLC from other neuroendocrine neoplasms and NSCLC. Conclusion: CD56 and quantitative Ki-67 along with cytomorphology is a robust immunohistochemical panel to differentiate SCLC from other neuroendocrine neoplasms and NSCLC.

Molecular alterations in non-small cell lung carcinomas of the young.

BACKGROUND AND IMPORTANCE:Intraspinal synovial cysts are uncommon causes of back and radicular leg pain. Usually associated with degenerative spinal disease, these juxtafacet cysts are usually located in the lumbar spine and may rarely undergo intracystic hemorrhage. The pathogenesis of these cysts are unclear, and risk factors that may contribute to hemorrhagic complications are largely unknown. CLINICAL PRESENTATION:A 68-year-old man presented to the clinic 4 months after a fall on ice with persistent back pain and lumbar radiculopathy. A week after the initial clinic consultation, the patient presented to the emergency room with increased pain and worsening weakness in the left foot. An emergent magnetic resonance image showed thecal sac compression secondary to a large, juxtafacet cyst that was hyperintense on T1-weighted and hypointense on T2-weighted images. Lumbar decompressive laminectomies were performed at L3 and L4 with cyst removal and stabilization. CONCLUSION:We present the eighth reported case of a hemorrhagic juxtafacet cyst secondary to physical trauma, the second in which the patients symptoms acutely worsened several months after the initial insult without new trauma. We also present summary statistics of the 31 cases of hemorrhagic juxtafacet cysts reported in the literature and propose a putative mechanism that may account for the development and progression of symptoms in some patients.

Giant cell tumor of tendon sheath: Cytomorphologic and radiologic findings in 41 patients

OBJECTIVE: To estimate whether there are placental histopathologic abnormalities associated with neonatal periventricular leukomalacia (PVL), a major precursor of cerebral palsy. METHODS: This is a case-control study of 167 neonates born between 23 and 34 weeks of gestation diagnosed with PVL by head ultrasonography within 6 weeks of birth, and 167 control neonates without neurologic morbidity matched by gestational age. Placentas for both case neonates and control neonates were reviewed by two perinatal pathologists who were blinded to neonatal course. RESULTS: Neonates with PVL were significantly more likely to have positive neonatal blood (28.7%, 16.8%, P=.001) and cerebrospinal fluid (14.4%, 4.8%, P=.007) cultures. The ratio of placental weight to birth weight did not differ between groups, but neonates with PVL had significantly more chronic diffuse capsular deciduitis (20.4%, 10.8%, P=.02) and capsular decidual plasma cells (8.4%, 2.4%, P=.02). Conditional logistic regression adjusting for birth weight and the presence of multiple gestation in the identification of PVL showed a significant increase for diffuse capsular deciduitis (P=.02) and capsular decidual plasma cells (P=.03). CONCLUSION: Periventricular leukomalacia has a significant but weak association with chronic diffuse capsular deciduitis and the presence of capsular decidual plasma cells, evidence of chronic infection but not histologic acute chorioamnionitis. LEVEL OF EVIDENCE: II

Elastofibroma: cytomorphologic, histologic, and radiologic findings in five cases.

Lung cancer is the leading cause of cancer death in the United States. Gene alterations are significant in lung tumorigenesis, with certain genes (Kristen rat sarcoma viral oncogene homolog (KRAS), epidermal growth factor receptor [EGFR], anaplastic lymphoma kinase [ALK], and B-Raf proto-oncogene, serine/threonine kinase (BRAF)) possessing alterations important in the prognosis and treatment of lung adenocarcinoma. Mutation frequencies are affected by different patient factors, such as smoking history, age, and race. Because most lung cancers occur in patients older than age of 50 years, few studies have examined molecular alterations present in these younger patients. The pathology database was searched for patients age of 50 years or younger with non-small cell lung carcinomas (NSCLCs) tested for EGFR, ALK, KRAS, and/or BRAF alterations. A total of 53 cases were identified. The mean patient age was 44.4 years old, and there were 19 men and 34 women. Of the tumors, 11.6% had ALK rearrangements, 25.5% had KRAS mutations, and 20.0% had EGFR mutations. No BRAF mutations were identified in the 28 cases tested. All but 1 (92% [12/13]) tumor with KRAS mutation were from women patients. A smoking history of greater than 5 pack-years was associated with KRAS mutations and negatively associated with EGFR mutations and ALK translocation. The frequencies of EGFR mutation and ALK translocation in the study cohort are greater than the reported frequencies among NSCLC from adults of all ages in the United States but less than the reported frequencies among NSCLC from East Asian young adults. The frequency of KRAS mutation is significantly greater than what was previously found in young Japanese patients.

A panel of novel detection and prognostic methylated DNA markers in primary non–small cell lung cancer and serum DNA

Giant cell tumor of tendon sheath (GCTTS) is a common soft tissue lesion and presents as a firm, slow‐growing, non‐tender mass adjacent to the tendon sheath. It can be further classified into diffuse or localized types based on its growth pattern. Using cytomorphologic analysis, we assessed the feasibility of fine‐needle aspiration (FNA) as an initial diagnostic modality for GCTTS. Forty‐one cases of image‐guided FNA of GCTTS were retrospectively retrieved from the archives of The Johns Hopkins Hospital. Clinical information, imaging studies, histopathology, and other ancillary studies were also reviewed. The majority of the cytology specimens demonstrated hypercellularity. A uniform population of spindled to polygonal stromal cells constituted more than half of the cellularity. Other cell types frequently present included multinucleated giant cells, hemosiderin‐laden macrophages, and foamy histiocytes. Nuclear grooves or intranuclear pseudo‐inclusions present in stromal cells were also distinctive cytomorphologic features, but only present in less than a quarter of the cases. Our study has shown the usefulness and accuracy of imaging‐guided FNA as a diagnostic tool for GCTTS. Diagnostic accuracy can be optimized with a thorough review of clinical history, careful physical examination, and radiologic correlation. Diagn. Cytopathol. 2012;