Israh Akhtar

Age-appropriate use of human papillomavirus vaccines in the U.S.

Cervical infections by approximately 15 cancer-associated (carcinogenic) human papillomavirus (HPV) genotypes cause virtually all cervical cancer and its immediate precursor lesions worldwide. Prophylactic vaccines against human papillomavirus (HPV) types HPV16 and HP18, which cause 70% of cervical cancer worldwide, hold great promise for reducing the burden of cervical cancer worldwide. However, current HPV vaccines prevent future infections and related cervical abnormalities and do not treat pre-existing HPV infections. In the U.S., HPV vaccine introduction should be considered in the context of a very successful cervical cancer screening program that has reduced the rates of cervical cancer by 75% or more. Thus, HPV vaccines will only prevent an incremental number of additional cervical cancers in the U.S. The introduction of HPV vaccines can also prevent other HPV-related sequelae, most importantly cervical intraepithelial neoplasia grade 2 or 3 (CIN2/3), which precede the development of cervical cancer and require clinical follow-up and treatment. Examining data from 7 clinical centers in the U.S., the median age of CIN2/3 is typically between 25 and 30 years of age in 2007; if screen-detected CIN2/3 develops on average 5-10 years after the causal infection is acquired, HPV vaccination will only prevent a significant proportion of CIN2/3 if it is given to women before the age of 26 and more so if given to women 18 and younger. It is increasingly evident that prophylactic HPV vaccines will provide the greatest public health or population benefit only when delivered to adolescent, mostly HPV-naive women.

Hybrid Capture 2 human papillomavirus DNA testing for women with atypical squamous cells of undetermined significance papanicolaou results in SurePath and ThinPrep specimens

Human papillomavirus (HPV) DNA testing using Hybrid Capture 2 assay with ThinPrep Papanicolaou (Pap) collection is the only US Food and Drug Administration‐approved method for the triage of women with atypical squamous cells of undetermined significance (ASCUS). Although SurePath Pap collection has been used for Hybrid Capture 2 HPV DNA testing, clinical validation of this method has been scarce.

Fine needle aspiration biopsy of vertebral and paravertebral lesions: retrospective study of 124 cases.

OBJECTIVE To evaluate the diagnostic value of image-guided fine needle aspiration biopsy (FNAB) in the diagnosis and management of vertebral and paravertebral lesions and to review similar studies in the literature. STUDY DESIGN One hundred twenty-four FNAB cases (113 [corrected] patients) of vertebral and paravertebral lesions occurring over a 10-year period were retrieved from the archives of the University of Mississippi Medical Center for review and clinico-radiologic correlation. Thirty-four of the cases included a concurrent core needle biopsy sample, 15 cases had subsequent surgical specimens, while 32 cases had previously established malignancy. The age range was 11 days to 91 years (mean, 46 years), with 57 male patients and 56 female. RESULTS One hundred five cases were vertebral lesions, and 19 cases were paravertebral lesions. FNAB diagnosis were malignant in 33.87% of cases, benign in 5.64%, suspicious in 4.03%, infectious/inflammatory and degenerative in 12.91%, unsatisfactory in 16.13% and negative in 27.42%. The overall sensitivity of the procedure was 89.3% and the specificity, 93.8%. The positive predictive value was 95.7% and negative predictive value, 85.2%. CONCLUSION FNAB is an effective means of establishing a definitive diagnosis of vertebral and paravertebral lesions, allowing appropriate patient management. Cell blocks, core biopsies and ancillary studies are useful adjuncts in rendering the diagnosis.

MTA1‐activated Epi‐microRNA‐22 regulates E‐cadherin and prostate cancer invasiveness

We have previously shown that metastasis‐associated protein 1 (MTA1), a chromatin remodeler, plays an important role in prostate cancer invasiveness, likely through regulation of epithelial‐to‐mesenchymal transition. Here, we identified miR‐22 as an epigenetic‐microRNA (Epi‐miR) directly induced by MTA1 and predicted to target E‐cadherin. Loss‐of‐function and overexpression studies of MTA1 reinforced its regulatory role in miR‐22 expression. MiR‐22 directly targets the 3′‐untranslated region of E‐cadherin, and ectopic overexpression of miR‐22 diminishes E‐cadherin expression. Overexpression of miR‐22 in prostate cancer cells promotes cell invasiveness and migration. Meta‐analysis of patient tumor samples indicates a positive correlation between MTA1 and miR‐22, supporting their inhibitory effect on E‐cadherin expression. Our findings implicate the MTA1/Epi‐miR‐22/E‐cadherin axis as a new epigenetic signaling pathway that promotes tumor invasion in prostate cancer.

Unusual presentation of chronic myelogenous leukemia as multiple skin chloromas: report of a case with clinical and cytologic correlation.

BACKGROUND Chronic myelogenous leukemia (CML) presenting as multiple skin chloromas is an extremely rare manifestation. Though often seen in acute myelogenous leukemia, to date there have been no reported cases of CML presenting as multiple skin chloromas in the chronic phase. Chloromas in blastic phase of CML at different body sites have been reported previously. CASE A 53-year-old African American male presented to his primary care provider with multiple skin nodules. A complete blood cound showed a high white cell count, for which he was transferred to a university tertiary care center. Fine needle aspiration (FNA) of the skin lesion revealed cellular smears consisting of immature myeloid cells of CML. Based on these findings, and with clinical correlation, a preliminary diagnosis of chloroma was made and confirmed by ancillary studies. CONCLUSION This rare manifestation should alert a clinician to include CML in chronic phase in the differential diagnosis of patients presenting with multiple nonpigmented, nonpruritic skin nodules. FNA with ancillary studies can provide a rapid diagnosis.

Additional diagnostic features of mammary analogue secretory carcinoma on cytology

Mammary analogue secretory carcinoma (MASC)/secretory carcinoma is a recently described tumour with ETV6 translocation. Most published data on MASC are based on retrospective review of previously diagnosed low-grade adenocarcinomas, acinic cell carcinoma (AciCC) and low-grade mucoepidermoid carcinomas (MEC) of the salivary gland that were eventually shown to harbour ETV6 translocation. Overlapping morphological features and lack of familiarity with the tumour possibly contributes to the tumour being under recognised. In this case report, we describe ETV6-positive MASC in an 18-year-old man. In addition to vacuolated cells/histiocytoid cells and colloid-like material in the background we noticed nuclear membrane irregularities, nuclear grooving and hyalinised tissue fragments in the cell block. These additional features can serve as important diagnostic clues in making a diagnosis of MASC on cytology.

Targeting MTA1/HIF-1α signaling by pterostilbene in combination with histone deacetylase inhibitor attenuates prostate cancer progression

The metastasis‐associated protein 1(MTA1)/histone deacetylase (HDAC) unit is a cancer progression‐related epigenetic regulator, which is overexpressed in hormone‐refractory and metastatic prostate cancer (PCa). In our previous studies, we found a significantly increased MTA1 expression in a prostate‐specific Pten‐null mouse model. We also demonstrated that stilbenes, namely resveratrol and pterostilbene (Pter), affect MTA1/HDAC signaling, including deacetylation of tumor suppressors p53 and PTEN. In this study, we examined whether inhibition of MTA1/HDAC using combination of Pter and a clinically approved HDAC inhibitor, SAHA (suberoylanilide hydroxamic acid, vorinostat), which also downregulates MTA1, could block prostate tumor progression in vivo. We generated and utilized a luciferase reporter in a prostate‐specific Pten‐null mouse model (Pb‐Cre+; Ptenf/f; Rosa26Luc/+) to evaluate the anticancer efficacy of Pter/SAHA combinatorial approach. Our data showed that Pter sensitized tumor cells to SAHA treatment resulting in inhibiting tumor growth and additional decline of tumor progression. These effects were dependent on the reduction of MTA1‐associated proangiogenic factors HIF‐1α, VEGF, and IL‐1β leading to decreased angiogenesis. In addition, treatment of PCa cell lines in vitro with combined Pter and low dose SAHA resulted in more potent inhibition of MTA1/HIF‐1α than by high dose SAHA alone. Our study provides preclinical evidence that Pter/SAHA combination treatment inhibits MTA1/HIF‐1α tumor‐promoting signaling in PCa. The beneficial outcome of combinatorial strategy using a natural agent and an approved drug for higher efficacy and less toxicity supports further development of MTA1‐targeted therapies in PCa.

Follicular Thyroid Carcinoma Metastatic to the Kidney: Report of a Case with Cytohistologic Correlation

Here we report a case of a 45-year-old female who underwent thyroidectomy for thyroid cancer and presented 20 years later with a left renal mass. CT-guided core biopsy was performed, and imprints and histologic sections of the biopsy showed cells resembling thyroid follicular cells with a background containing colloid. Immunohistochemistry revealed positivity for thyroglobulin and thyroid transcription factor 1, consistent with metastatic follicular thyroid carcinoma (FTC). The patient later underwent radical nephrectomy; histologic sections of the resected tumor revealed an encapsulated lesion morphologically similar to the biopsy specimen. Thyroid metastases to the kidney are extremely rare and are often detected during postthyroidectomy surveillance by elevation in thyroid hormone levels, 131I scintigraphy, or 18F-fluorodeoxyglucose uptake in positron emission tomography studies. Treatment involves total thyroidectomy, resection of the metastatic foci, and 131I therapy. The differential diagnoses of renal metastasis of FTC include the encapsulated follicular variant of papillary thyroid carcinoma (PTC), which possesses some of the nuclear features seen in conventional PTC but may occasionally be indistinguishable from FTC in cytologic preparations, and renal lesions such as benign thyroidization of the kidney and thyroid-like follicular carcinoma of the kidney, which mimic FTC in histologic appearance but do not stain with thyroid markers.

Ductopapillary apocrine carcinoma of the eyelid metastatic to the parotid gland: report of a case diagnosed by fine-needle aspiration biopsy.

Ductopapillary apocrine carcinoma (DPAC) of the eyelid is a rare malignant neoplasm in the periocular region. The relative rarity of this tumor is a diagnostic challenge to the cytopathologist, especially when present as a metastatic lesion to an intraparotid lymph node, where the differential diagnosis includes primary parotid neoplasms, as well as various other metastatic malignancies. There are only a few reported cases of recurrent and metastatic DPAC of the eyelid, and to our knowledge, metastatic DPAC diagnosed by fine‐needle aspiration biopsy (FNAB) has not been described. We report a case of a 65‐year‐old African‐American male with a history of ductopapillary apocrine adenocarcinoma of the eyelid, diagnosed 6 weeks ago now presenting with a recurrence in the same area. Magnetic resonance imaging of the head and neck revealed an intraparotid mass also. FNAB of the parotid mass showed a well‐differentiated papillary adenocarcinoma with a cystic component, similar to a previously excised ductopapillary apocrine adenocarcinoma of the eyelid. Diagn. Cytopathol. 2009.

Cyto-histological correlation of Xp11.2 translocation/TFE3 gene fusion associated renal cell carcinoma: Report of a case with review of literature

The MiT family translocation renal cell carcinomas (RCCs) are relatively rare in comparison to the conventional RCC. The cytologic features overlap with conventional clear cell RCC and papillary RCCs, thereby making the diagnosis extremely challenging. Here, we describe a case of TFE3 translocation associated RCC in a 58‐year‐old patient, with emphasis on cytomorphologic features and clues toward this diagnostic entity. Correlating the cytohistologic findings and review of touch imprints revealed that presence of hyaline nodules resembling leisegang rings and psammoma bodies in cytologic smears from kidney tumors serve as an important clue in raising a suspicion for the diagnosis of MiT family translocation RCCs.