Cod Liver Oil, but Not Retinoic Acid, Treatment Restores Bone Thickness in a Vitamin A-Deficient Rat.

Vitamin A plays a prominent role for maintaining optimal bone status, but its impact upon the bone in response to vitamin A deficiency is not well defined. The purpose of this study was to evaluate how replenishing vitamin A by either whole food cod liver oil (COD) or the active metabolite of vitamin A, retinoic acid (RA), altered bone thickness of vitamin A-deficient (VAD) rats. Weanling rats were administered a control diet (CTRL) or VAD diet for 9 weeks. This was followed by four weeks of treatment in which the VAD group was divided into the following 4 subgroups: (1) VAD (9 weeks)-VAD (4 weeks); (2) VAD-CTRL; (3) VAD-COD; and (4) VAD-RA. Compared to controls, VAD rats had thicker bones which showed marked dysplasia. VAD-rats treated with COD produced a thinner bone that was not significantly different from that of untreated rats. In contrast, RA did not significantly change the thicker bone, and also had significantly greater periosteal and endosteal osteoblast numbers compared to VAD-COD. Active osteoclasts were not detected in VAD rats, nor during the treatment period. These findings suggest that the abnormal bone thickness in VAD rats appears to be more effectively restored to bone thickness of untreated control rats when treated with COD.

Diagnosis of intrathyroidal ectopic thymus in thyroid fine needle aspiration samples.

AIMS: Intrathyroidal ectopic thymus (ITET) is a rare cause of paediatric thyroid nodules. Although ultrasonography of ITET demonstrates a characteristic appearance similar to that of normal thymus, accurate differentiation from other thyroid nodule etiologies by ultrasonography is difficult, and so that fine needle aspiration (FNA) is usually performed for further analysis. The aim of this study was to evaluate the utility of flow cytometry (FCM) in confirming the diagnosis of ITET in thyroid FNA samples. METHODS: Five cases of ITET were retrieved from our thyroid FNA database within a 3-year period. Their clinical information, ultrasonographic features, cytology and FCM findings were retrospectively reviewed. The FCM results were compared with those of 22 T-cell acute lymphoblastic leukaemia/lymphoblastic lymphoma (T-ALL/LBL) cases. RESULTS: The FNA smears of all five ITET cases demonstrated abundant lymphocytes of variable sizes, which included some immature lymphoid cells. No Hassall's bodies or atypical epithelioid cells were recognised. By multicolour FCM analysis including antibodies against CD1a, CD2, CD3, CD4, CD5, CD7, CD8, CD10, CD34, TDT and TCR, all ITET cases showed antigen expression patterns consistent with normal thymocyte maturation. All T-ALL/LBL cases exhibited significant immunophenotypic aberrancy. CONCLUSIONS: The diagnosis of ITET based on FNA cytology is often inconclusive. The presence of immature lymphocytes often raises the concern for LBL. FCM with adequate antigen coverage can reliably distinguish ITET from T-ALL/LBL and make the diagnosis of ITET in FNA samples. Avoiding unnecessary further invasive procedures, providing reassurance to clinician and patient, the accurate diagnosis of ITET by FCM in FNA samples is clinically important.

Preclinical Safety Evaluation of HIV-1 gp120 Responsive Microbicide Delivery System in C57BL/6 Female Mice.

Many novel vaginal/rectal microbicide formulations failed clinically due to safety concerns, indicating the need for the early investigation of lead microbicide formulations. In this study, the preclinical safety of an HIV-1 gp120 and mannose responsive microbicide delivery system (MRP) is evaluated in C57BL/6 mice. MRP was engineered through the layer-by-layer coating of calcium carbonate (CaCO3) with Canavalia ensiformis lectin (Con A) and glycogen. MRP mean particle diameter and zeta potential were 857.8 ± 93.1 nm and 2.37 ± 4.12 mV, respectively. Tenofovir (TFV) encapsulation and loading efficiencies in MRP were 70.1% and 16.3% w/w, respectively. When exposed to HIV-1 rgp120 (25 µg/mL), MRP released a significant amount of TFV (∼5-fold higher) in vaginal and seminal fluid mixture compared to the control (pre-exposure) level (∼59 µg/mL) in vaginal fluid alone. Unlike the positive control treated groups (e.g., nonoxynol-9), no significant histological damages and CD45+ cells infiltration were observed in the vaginal and major reproductive organ epithelial layers. This was probably due to MRP biocompatibility and its isosmolality (304.33 ± 0.58 mOsm/kg). Furthermore, compared to negative controls, there was no statistically significant increase in pro-inflammatory cytokines such as IL1α, Ilß, IL7, IP10, and TNFα. Collectively, these data suggest that MRP is a relatively safe nanotemplate for HIV-1 gp120 stimuli responsive vaginal microbicide delivery system.

Spray-Dried Thiolated Chitosan-Coated Sodium Alginate Multilayer Microparticles for Vaginal HIV Microbicide Delivery.

It is hypothesized that novel thiolated chitosan-coated multilayer microparticles (MPs) with enhanced drug loading are more mucoadhesive than uncoated MPs and safe in vivo for vaginal delivery of topical anti-HIV microbicide. Formulation optimization is achieved through a custom experimental design and the alginate (AG) MPs cores are prepared using the spray drying method. The optimal MPs are then coated with the thiolated chitosan (TCS) using a layer-by-layer method. The morphological analysis, in situ drug payload, in vitro drug release profile, and mucoadhesion potential of the MPs are carried out using scanning electron microscopy, solid-state 31P NMR spectroscopy, UV spectroscopy, fluorescence imaging and periodic acid Schiff method, respectively. The cytotoxicity and preclinical safety of MPs are assessed on human vaginal (VK2/E6E7) and endocervical (End1/E6E7) epithelial cell lines and in female C57BL/6 mice, respectively. The results show that the MPs are successfully formulated with an average diameter ranging from 2 to 3 µm with a drug loading of 7-12% w/w. The drug release profile of these MPs primarily follows the Baker-Lonsdale and Korsmeyer-Peppas models. The MPs exhibit high mucoadhesion (20-50 folds) compared to native AGMPs. The multilayer MPs are noncytotoxic. Histological and immunochemical analysis of the mice genital tract shows neither signs of damage nor inflammatory cell infiltrate. These data highlight the potential use of TCS-coated AG-based multilayer MPs templates for the topical vaginal delivery of anti-HIV/AIDS microbicides.

Stimuli-sensitive thiolated hyaluronic acid based nanofibers: synthesis, preclinical safety and in vitro anti-HIV activity.

AIM: To develop a seminal enzyme bioresponsive, mucoadhesive nanofibers (NFs) as safe and effective nanocarriers for the prevention of HIV vaginal transmission. METHODS: A novel thiolated hyaluronic acid (HA-SH) polymer was synthesized to fabricate tenofovir (TFV)-loaded electrospun NFs (HA-SH-NFs) and characterized in vitro/in vivo. RESULTS: A triggered drug release (87% w/w) from the engineered HA-SH-NFs (mean diameter ∼75 nm) occured within 1 h under the influence of seminal hyaluronidase enzyme. HA-SH-NFs were noncytotoxic, induced no damage on the C57BL/6 mice genital-tract and other organs. No significant CD45 cell-infiltration and changes in cytokines level in cervicovaginal tissues were observed. HA-SH-NFs significantly enhanced both TFV retention and bioavailability in vaginal tissue compared with the 1% TFV-gel. The anti-HIV activity of TFV (on pseudotyped virus followed by luciferase assay) was not adversely affected by the electrospinning process. CONCLUSION: HA-SH-NFs developed in this study could potentially serve as a safe nanotemplate for topical intravaginal delivery of HIV/AIDS microbicides.

Tenofovir Containing Thiolated Chitosan Core/Shell Nanofibers: In Vitro and in Vivo Evaluations.

It is hypothesized that thiolated chitosan (TCS) core/shell nanofibers (NFs) can enhance the drug loading of tenofovir, a model low molecular weight and highly water-soluble drug molecule, and improve its mucoadhesivity and in vivo safety. To test this hypothesis, poly(ethylene oxide) (PEO) core with TCS and polylactic acid (PLA) shell NFs are fabricated by a coaxial electrospinning technique. The morphology, drug loading, drug release profiles, cytotoxicity and mucoadhesion of the NFs are analyzed using scanning and transmission electron microscopies, liquid chromatography, cytotoxicity assays on VK2/E6E7 and End1/E6E7 cell lines and Lactobacilli crispatus, fluorescence imaging and periodic acid colorimetric method, respectively. In vivo safety studies are performed in C57BL/6 mice followed by H&E and immunohistochemical (CD45) staining analysis of genital tract. The mean diameters of PEO, PEO/TCS, and PEO/TCS-PLA NFs are 118.56, 9.95, and 99.53 nm, respectively. The NFs exhibit smooth surface. The drug loading (13%-25%, w/w) increased by 10-fold compared to a nanoparticle formulation due to the application of the electrospinning technique. The NFs are noncytotoxic at the concentration of 1 mg/mL. The PEO/TCS-PLA core/shell NFs mostly exhibit a release kinetic following Weibull model (r2 = 0.9914), indicating the drug release from a matrix system. The core/shell NFs are 40-60-fold more bioadhesive than the pure PEO based NFs. The NFs are nontoxic and noninflammatory in vivo after daily treatment for up to 7 days. Owing to their enhanced drug loading and preliminary safety profile, the TCS core/shell NFs are promising candidates for the topical delivery of HIV/AIDS microbicides such as tenofovir.

Conjunctival myxoma: a synopsis of a rare ocular tumor.

Conjunctival myxoma is an exceptionally rare, slow-growing, benign neoplasm of primitive mesenchyme origin. Forty-one cases of conjunctival myxoma from a literature review, including the authors' case, are listed. The usual clinical history is a painless mass appearing during months to years. Grossly, the tumor is a well-circumscribed, cystlike, gelatinous, yellow-to-pink, translucent-to-solid mass. Microscopically, the hypocellular tumor contains stellate- and spindle-shaped cells in a mucoid stroma with abundant hyaluronic acid mucopolysaccharides. Vimentin and α-smooth muscle actin highlight the spindle and stellate cells. S100 protein and desmin are negative for the tumor cells. Treatment is complete surgical excision, with no recurrence reported in the follow-up period. Notably, conjunctival myxoma may be associated with Carney complex, an autosomal-dominant disorder associated with skin pigmentation, endocrine abnormalities, and myxoma of the heart and eye. Physicians should appreciate this unique ocular tumor because of its potential association with Carney complex.

Evidence of BRAF V600E in indeterminate cell tumor and interdigitating dendritic cell sarcoma.

BRAF V600E mutations have been reported in several histiocytic and dendritic cell neoplasms. In this case series, we report BRAF V600E-positive histiocytic and dendritic cell neoplasms in association with lymphomas and lymphoid proliferations. This is a review of cases with immunohistochemistry for BRAF V600E, with additional immunohistochemistry to categorize tumors. We report the first case of BRAF V600E-positive indeterminate cell tumor in association with angioimmunoblastic T-cell lymphoma. We also report a case of BRAF V600E-positive interdigitating dendritic cell sarcoma in a patient with positive B-cell polymerase chain reaction. It is unclear if these neoplasms developed as transdifferentiation of lymphoid neoplasms or if they developed independently. These cases illustrate the expanding spectrum of BRAF V600E-positive histiocytic and dendritic cell tumors and suggest that attention should be paid to lymphomas for possible coincident presentation of these disorders.

Resveratrol inhibits estrogen-induced breast carcinogenesis through induction of NRF2-mediated protective pathways.

The importance of estrogens in the etiology of breast cancer is widely recognized. Estrogen-induced oxidative stress has been implicated in this carcinogenic process. Resveratrol (Res), a natural antioxidant phytoestrogen has chemopreventive effects against a variety of illnesses including cancer. The objective of the present study was to characterize the mechanism(s) of Res-mediated protection against estrogen-induced breast carcinogenesis. Female August Copenhagen Irish rats were treated with 17ß-estradiol (E2), Res and Res + E2 for 8 months. Cotreatment of rats with Res and E2 inhibited E2-mediated proliferative changes in mammary tissues and significantly increased tumor latency and reduced E2-induced breast tumor development. Resveratrol treatment alone or in combination with E2 significantly upregulated expression of nuclear factor erythroid 2-related factor 2 (NRF2) in mammary tissues. Expression of NRF2-regulated antioxidant genes NQO1, SOD3 and OGG1 that are involved in protection against oxidative DNA damage was increased in Res- and Res + E2-treated mammary tissues. Resveratrol also prevented E2-mediated inhibition of detoxification genes AOX1 and FMO1. Inhibition of E2-mediated alterations in NRF2 promoter methylation and expression of NRF2 targeting miR-93 after Res treatment indicated Res-mediated epigenetic regulation of NRF2 during E2-induced breast carcinogenesis. Resveratrol treatment also induced apoptosis and inhibited E2-mediated increase in DNA damage in mammary tissues. Increased apoptosis and decreased DNA damage, cell migration, colony and mammosphere formation in Res- and Res + E2-treated MCF-10A cells suggested a protective role of Res against E2-induced mammary carcinogenesis. Small-interfering RNA-mediated silencing of NRF2 inhibited Res-mediated preventive effects on the colony and mammosphere formation. Taken together, these results suggest that Res inhibits E2-induced breast carcinogenesis via induction of NRF2-mediated protective pathways.

The usefulness of S100P, mesothelin, fascin, prostate stem cell antigen, and 14-3-3 sigma in diagnosing pancreatic adenocarcinoma in cytological specimens obtained by endoscopic ultrasound guided fine-needle aspiration.

Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) of the pancreas is an efficient and minimally invasive procedure for the diagnosis and staging of pancreatic adenocarcinoma. Because of some limitations of EUS-FNA in diagnosis of well-differentiated or early stage cancers, the purpose of this study is to assess the added benefit of immunohistochemistry. We studied five proteins overexpressed in pancreatic adenocarcinoma, namely, prostate stem cell antigen, fascin, 14-3-3 sigma, mesothelin and S100P utilizing immunohistochemistry on paraffin sections from cellblocks obtained by EUS-FNA. Sixty-two cases of EUS-FNA of the pancreas that had follow-up histological and/or clinical diagnosis and sufficient material in cell blocks were included. Using histological diagnosis and/or clinical outcome as the reference standard, EUS-FNA shows the highest sensitivity (95%) and specificity (91%) and is superior to any marker in this study. Among five antibodies, S100P reveals the best diagnostic characters showing 90% of sensitivity and 67% of specificity. Fascin shows high specificity (92%) but low sensitivity (38%). Mesothelin has a moderate sensitivity (74%) and low specificity (33%), PSCA and 14-3-3 show high sensitivity but zero specificity. S100P and mesothelin were useful in nine indeterminate cases. S100P correctly predicted six of seven cancers and one of one without cancer and mesothelin correctly diagnosed five of seven cancers and one of two noncancers in this group. EUS-FNA cytomorphology is superior to any of the immunohistochemical markers used in this study. Use of S100P and mesothelin in cytologically borderline cases can increase the diagnostic accuracy in this group.

Targeted disruption of MCPIP1/Zc3h12a results in fatal inflammatory disease.

Previous studies using MCP-induced protein 1 (MCPIP1)/Zc3h12a-deficient mice suggest that MCPIP1 is an important regulator of inflammation and immune homeostasis. However, the characterization of the immunological phenotype of MCPIP1-deficient mice has not been detailed. In this study, we performed evaluation through histological, flow cytometric, enzyme-linked immunosorbent assay and real-time PCR analysis and found that targeted disruption of MCPIP1 gene leads to fatal, highly aggressive and widespread immune-related lesions. In addition to previously observed growth retardation, splenomegaly, lymphoadenopathy, severe anemia and premature death, MCPIP1-deficient mice showed disorganization of lymphoid organs, including spleen, lymph nodes and thymus, and massive infiltration of lymphocytes, macrophages and neutrophils into many other non-lymphoid organs, primarily in lungs and liver. Flow cytometric analysis found significant increase in activated and differentiated T cells in peripheral blood and spleen of MCPIP1-deficient mice. Moreover, heightened production of inflammatory cytokines from activated macrophages and T cells were observed in MCPIP1-deficient mice. Interestingly, treatment of MCPIP1-deficient mice with antibiotics resulted in significant improvement of life span and a decrease in inflammatory syndrome. Taken together, these results suggest a prominent role for MCPIP1 in the control of inflammation and immune homeostasis.

Dietary Flaxseed Oil Protects against Bleomycin-Induced Pulmonary Fibrosis in Rats.

Bleomycin, a widely used antineoplastic agent, has been associated with severe pulmonary toxicity, primarily fibrosis. Previous work has shown a reduction in bleomycin-induced lung pathology by long-chain omega-3 fatty acids. Treatment by short-chain omega-3 fatty acids, α-linolenic acid, found in dietary flaxseed oil may also reduce lung fibrosis, as previously evidenced in the kidney. To test this hypothesis, 72 rats were divided between diets receiving either 15% (w/w) flaxseed oil or 15% (w/w) corn oil (control). These groups were further divided to receive either bleomycin or vehicle (saline) via an oropharyngeal delivery, rather than the traditional intratracheal instillation. Lungs were harvested at 2, 7, and 21 days after bleomycin or saline treatment. Animals receiving flaxseed oil showed a delay in edema formation (P = 0.025) and a decrease in inflammatory cell infiltrate and vasculitis (P = 0.04 and 0.007, resp.). At days 7 and 21, bleomycin produced a reduction in pulmonary arterial lumen patency (P = 0.01), but not in rats that were treated with flaxseed oil. Bleomycin-treated rats receiving flaxseed oil had reduced pulmonary septal thickness (P = 0.01), signifying decreased fibrosis. Dietary flaxseed oil may prove beneficial against the side effects of this highly effective chemotherapeutic agent and its known toxic effects on the lung.

Primary chondrosarcoma of the breast: report of a case and review of the literature.

Sarcomas of the breast are rare, comprising 1% of all breast tumors. Primary chondrosarcomas of the breast account for an extremely rare subset of such tumors, with few reports in the literature. We report the case of a 52 year-old woman with a primary chondrosarcoma of the breast and review the current literature.

Ganglioneuroma presenting as a paraesophageal mass lesion diagnosed by endoscopic ultrasound-guided fine needle aspiration cytology: a case report.

BACKGROUND: Endoscopic ultrasound-guided fine needle aspiration is a well-established modality in detection and diagnosis of mediastinal lesions. Ganglioneuroma is a benign, rare, soft tissue neoplasm arising from sympathetic ganglion cells, and complete surgical resection is considered to be curative. Ganglioneuroma in a surgical specimen is a straightforward diagnosis; however, due to the infrequent occurrence of this entity, diagnosis by fine needle aspiration is more challenging. CASE: A case of paraesophageal ganglioneuroma was diagnosed by endoscopic ultrasound-guided fine needle aspiration. A 75-year-old man with a history of adenocarcinoma of the lung was noted to have a mediastinal mass on chest computed tomography. Upper endosonography identified a 40x17-mm mass extrinsic to the thoracic esophagus. An endoscopic ultrasound-guided fine needle aspiration of the mass revealed intermingled fragments of spindle cells and ganglion cells admixed within a fibromyxoid stroma. Immunohistochemistry showed that both the spindle and ganglion cell components were positive for S-100 protein and negative for pancytokeratin. This immunohistochemical profile established both the neurogenic origin of the spindle and ganglion cells. CONCLUSION: Our case represents 1 of the few reported cases of ganglioneuroma diagnosed by fine needle aspiration cytology and the second case diagnosed under endoscopic ultrasound guidance.

The expression of TRMT2A, a novel cell cycle regulated protein, identifies a subset of breast cancer patients with HER2 over-expression that are at an increased risk of recurrence.

BACKGROUND: Over-expression of HER2 in a subset of breast cancers (HER2+) is associated with high histological grade and aggressive clinical course. Despite these distinctive features, the differences in response of HER2+ patients to both adjuvant cytotoxic chemotherapy and targeted therapy (e.g. trastuzumab) suggests that unrecognized biologic and clinical diversity is confounding treatment strategies. Furthermore, the small but established risk of cardiac morbidity with trastuzumab therapy compels efforts towards the identification of biomarkers that might help stratify patients. METHODS: A single institution tissue array cohort assembled at the Clearview Cancer Institute of Huntsville (CCIH) was screened by immunohistochemistry staining using a large number of novel and commercially available antibodies to identify those with a univariate association with clinical outcome in HER2+ patients. Staining with antibody directed at TRMT2A was found to be strongly associated with outcome in HER2+ patients. This association with outcome was tested in two independent validation cohorts; an existing staining dataset derived from tissue assembled at the Cleveland Clinic Foundation (CCF), and in a new retrospective study performed by staining archived paraffin blocks available at the Roswell Park Cancer Institute (RPCI). RESULTS: TRMT2A staining showed a strong correlation with likelihood of recurrence at five years in 67 HER2+ patients from the CCIH discovery cohort (HR 7.0; 95% CI 2.4 to 20.1, p < 0.0004). This association with outcome was confirmed using 75 HER2+ patients from the CCF cohort (HR 3.6; 95% CI 1.3 to 10.2, p < 0.02) and 64 patients from the RPCI cohort (HR 3.4; 95% CI 1.3-8.9, p < 0.02). In bivariable analysis the association with outcome was independent of grade, tumor size, nodal status and the administration of conventional adjuvant chemotherapy in the CCIH and RPCI cohorts. CONCLUSIONS: Studies from three independent single institution cohorts support TRMT2A protein expression as a biomarker of increased risk of recurrence in HER2+ breast cancer patients. These results suggest that TRMT2A expression should be further studied in the clinical trial setting to explore its predictive power for response to adjuvant cytotoxic chemotherapy in combination with HER2 targeted therapy.

Expression profiling of the ovarian surface kinome reveals candidate genes for early neoplastic changes.

OBJECTIVES: We tested the hypothesis that co-coordinated up-regulation or down-regulation of several ovarian cell surface kinases may provide clues for better understanding of the disease and help in rational design of therapeutic targets. STUDY DESIGN: We compared the expression signature of 69 surface kinases in normal ovarian surface epithelial cells (OSE), with OSE from patients at high risk and with ovarian cancer. RESULTS: Seven surface kinases, ALK, EPHA5, EPHB1, ERBB4, INSRR, PTK, and TGFbetaR1 displayed a distinctive linear trend in expression from normal, highrisk, and malignant epithelium. We confirmed these results using semiquantitative reverse transcription-polymerase chain reaction and tissue array of 202 ovarian cancer samples. A strong correlate was shown between disease-free survival and the expression of ERBB4. DNA sequencing revealed two novel mutations in ERBB4 in two cancer samples. CONCLUSIONS: A distinct subset of the ovarian surface kinome is altered in the transition from high risk to invasive cancer and genetic mutation is not a dominant mechanism for these modifications. These results have significant implications for early detection and targeted therapeutic approaches for women at high risk of developing ovarian cancer.

Ultrasound-guided fine needle aspiration cytology diagnosis of a foregut cyst in the thyroid: a case report.

BACKGROUND: Foregut cysts represent abnormal budding of the tracheobronchial anlage during embryogenesis. They occur most commonly in the mediastinum and pulmonary parenchyma and very seldom in the neck. CASE: A 42-year-old woman developed neck swelling and discomfort. An ultrasound scan showed a cystic nodule with a thick wall extending from the left lower pole of the thyroid gland. The material obtained from fine needle aspiration of the cyst demonstrated numerous detached ciliated tufts (DCTs) in a background of amorphous debris and degenerated cells. A diagnosis of ciliated cell remnants or DCTs consistent with a foregut cyst was made. CONCLUSION: Although this entity is rare, awareness of its occurrence in the thyroid gland may prevent unnecessary surgery.

Clear cell sarcoma of soft tissue metastatic to the ovaries: a heretofore unreported occurrence.

Clear cell sarcoma of soft tissue (CCSST) is a rare soft tissue neoplasm with marked variable tumor progression and prognosis. Although morphologically similar to malignant melanoma, CCSST can be distinguished by the presence of a t(12; 22)(q13; q12) and/or associated EWSR1-ATF1 chimeric gene. CCSST has an affinity for the extremities and is capable of metastasizing to a wide variety of sites including bone, lung, and lymph nodes and rarely to skin, liver, heart, muscle, and brain. Metastases have been known to occur as late as 29 years after initial presentation. We report a case of a 33-year-old woman who presented with bilateral ovarian cystic tumors, ascites, and pulmonary nodules. Her past medical history was significant for clear cell sarcoma of the left foot 2 years earlier. Bilateral salpingo-oophorectomy was performed and the light microscopic and immunohistochemical findings coupled with the detection of an EWSR1 rearrangement by fluorescence in situ hybridization were compatible with a diagnosis of CCSST metastases to the ovaries. To the best of our knowledge, this is the first reported case of CCSST metastatic to the ovaries.

Metastatic merkel cell carcinoma of the pancreas mimicking primary pancreatic endocrine tumor diagnosed by endoscopic ultrasound-guided fine needle aspiration cytology: a case report.

BACKGROUND: Merkel cell carcinoma (MCC) is a relatively infrequent, rapidly progressive and often fatal cutaneous malignancy exhibiting neuroendocrine differentiation. It has a penchant for local recurrence and distant metastasis to various sites, including regional lymph nodes, distant skin, lung, liver, testis and other rare organs, such as the pancreas. There are only 4 cases of MCC metastatic to the pancreas reported in the English-language literature, and they were all diagnosed by histology from pancreatic resection. CASE: A 79-year-old woman with a large pancreatic tail mass underwent endoscopic ultrasound guided fine needle aspiration (EUS-FNA). She had a history of MCC of the upper extremity with wide local excision 15 months earlier. Metastatic MCC was diagnosed based on the cytomorphology, characteristic immunohistochemical staining pattern, clinical history and comparison of the morphology with that of the primary tumor. CONCLUSION: The cytomorphology and immunohistochemical profile of this neoplasm mimicked a pancreatic endocrine tumor. We discuss the diagnostic pitfalls and differential diagnoses of the metastatic pancreatic MCC, highlighting the importance of thorough clinical history, attention to cytologic detail and corroborating immunohirtochemistry in arriving at the correct diagns. This is the first case ofa metastatic pancreatic MCC diagnosed by EUS-FNA cytology.

Placental Cryptococcus neoformans infection without neonatal disease: case report and review of the literature.

We report placental cryptococcosis in a woman with multidrug resistant human immunodeficiency virus (HIV) infection. She received antifungal therapy for cryptococcal meningitis prior to delivery. Cesarean section was performed with delivery of a single full-term male infant. There was no evidence of HIV or cryptococcal infection in the infant. The placenta grossly showed multiple white nodules. Microscopically, numerous encapsulated budding yeasts, morphologically consistent with cryptococci, were identified in the intervillous space and, to a lesser extent, in the chorionic villi. Cryptococcal infections are not uncommon, but only 2 cases of placental cryptococcosis have been reported. Our case is the 1st account documenting cryptococcal organisms within the chorionic villi, and yet there was no evidence of infection in the infant. Mother-to-fetal transmission of cryptococcal infection is not well defined. We review the literature and discuss its possible mechanisms.