Eosinophilic Cytoplasmic Inclusions Research Articles

Paneth Cell-Like Component in Prostate Cancer - Case Report.

Prostate adenocarcinoma with Paneth cell-like neuroendocrine differentiation is a rare entity. Foci of scattered cells and small clusters are found in the majority of described cases, although cases with predominant Paneth cell-like features have also been recorded. These cells contain eosinophilic cytoplasmic inclusions and lack androgen receptors, and are consequently immune to hormone therapy. It is, therefore, important for pathologists to recognize them. According to literature, clinical outcome depends on the standard grading of the conventional prostate cancer component. We report a case of a 54 year-old patient with prostatic adenocarcinoma showing Paneth cell-like neuroendocrine differentiation.

Autophagy defects and related genetic variations in renal cell carcinoma with eosinophilic cytoplasmic inclusions

The relationship between autophagy and tumour is well studied, but tumour cell morphological changes associated with autophagy defects are rarely reported, especially in renal cell carcinoma (RCC). We collected 10 renal tumour samples with characteristic eosinophilic cytoplasmic inclusions (ECIs) and found that the ECIs were majorly composed of sequestosome 1/P62, neighbor of BRCA1 gene 1 (NBR1), PEX14, and CATALASE1 (CAT1). Further, transmission electron microscopy analysis revealed that ECIs were aggregates of proteinaceous material and peroxisomes. These results confirmed that ECIs in RCCs were the products of autophagy defects. The presence of ECIs was correlated with high Fuhrman grade components of RCCs. Whole-exome sequencing (WES) and Sanger sequencing confirmed that tumours with ECIs showed somatic mutations or high frequency of genetic variations in autophagy-related (ATG) genes, such as ATG7, ATG5, and ATG10. These results indicate that nucleotide changes in ATG genes are associated with autophagy defect, ECI formation, and even tumour grade in RCCs.

Leiomyoma With Bizarre Nuclei: Clinical and Pathologic Features of 30 Patients.

Leiomyoma with bizarre nuclei (LBN) have significant cytologic atypia, but high mitotic rate and tumor cell necrosis are absent. Although it is a benign leiomyoma variant, recurrent cases have been described. In this study, we investigated the clinical and pathologic features of LBN and compared them with related studies. A total of 30 patients diagnosed with LBN in our department were included in this study. In all cases, clinical data (age, complaint, surgery type), macroscopic features (size, location, number of leiomyomas, necrosis, and hemorrhage), microscopic features (bizarre cell distribution, bizarre cell density, cellularity, mitotic rate, tumor margin, necrosis, nuclear pseudoinclusions, karyorrhectic nuclei, prominent eosinophilic nucleoli with perinucleolar clearing, cytoplasmic eosinophilic inclusions, staghorn vessels, and alveolar-type edema), and follow-up data (recurrence and survival period) were evaluated. The mean age of the patients was 49.76 yr (range: 38-89 yr). Twenty-two patients (73%) had undergone hysterectomy and 8 patients (27%) had undergone myomectomy. The mean tumor diameter was 6.12 cm (range: 0.5-25 cm). The tumor was intramural in 11 patients (37%), subserosal in 7 patients (23%), and submucosal in 4 patients (13%). Microscopically, the bizarre cell distribution was focal in 8 patients (27%), multifocal in 12 patients (40%), and diffuse in 10 patients (33%). Bizarre cell density was low in 15 patients (50%), intermediate in 8 patients (27%), and high in 7 patients (23%). The mean mitotic count was 1.4 (0-4) in 10 high-power fields, and the tumor margin was regular in all cases. We observed pseudoinclusions in 24 of 30 (80%) tumors, karyorrhectic nuclei in 21 of 30 tumors (70%), prominent eosinophilic nucleoli with perinucleolar clearing in 12 tumors (40%), cytoplasmic eosinophilic inclusions in 11 tumors (37%), staghorn vessels in 9 tumors (30%), and alveolar-type edema in 9 tumors (30%). In addition, we examined the follow-up records of 26 patients (average duration: 58.1 mo). One patient had a smooth muscle tumor in the L3-L4 paravertebral region at 67 mo after hysterectomy. This tumor did not share similar microscopic and immunohistochemical findings to the patient's earlier uterine tumor. The definitive diagnosis of uterine smooth muscle tumors is important for the determination of the prognosis of the patient and the most appropriate therapeutic approach. As in several recent studies, our series has shown that LBN has a benign clinical course. However, other malignant morphologic criteria such as high mitotic rate and tumor cell necrosis should be excluded in the diagnosis of LBN.

Methylation changes and aberrant expression of FGFR3 in Lewy body disease neurons

Lewy body disease (LBD) is characterized by accumulation of aggregated α-synuclein in the central nervous system as eosinophilic cytoplasmic inclusions called Lewy bodies. According to their distribution pattern, it is classified into brainstem LBD, limbic LBD and diffuse neocortical LBD. It has been reported that α-synuclein affects various points in the MAPK cascade but its relationship with FGF receptors, which are the most upstream of the pathway, has not been previously investigated. We discovered that among the four FGFRs, FGFR3 showed neuronal upregulation in LBD brains histopathologically. Further examination using neuron-specific methylome analysis revealed that the gene body of FGFR3 was hypermethylated in LBD, suggesting its increased transcription. Altered methylation was not observed in the non-neuronal genome. Altered methylation status was associated with the severity of α-synuclein pathology.

Utility of Cytokeratin7 Immunocytochemistry in the Cytopathological Diagnosis of Fibrolamellar Hepatocellular Carcinoma.

Objective:To distinguish fibrolamellar hepatocellular carcinoma (FL-HCC) variant from the conventional hepatocellular carcinoma (HCC) by cytology, immunocytochemistry, and morphometry.Study Design:Retrospective detailed cytomorphological, immunocytochemical, and morphometric analysis was performed in 6 cases of FL-HCC reported on fine needle aspiration. Cell block immunocytochemistry (CB-ICC) for CK7 and CD68 was performed in four cases. Morphometry was carried out with Cell A software. Area of the cell, nucleus and nucleolus was measured in 50 nuclei per case in 6 cases each of FL-HCC and HCC.Results:The mean age of patients with FL-HCC was 19 years and all had normal serum alpha-fetoprotein levels. Fine needle aspiration smears showed large polygonal cells with abundant cytoplasm, vesicular nucleus and prominent nucleolus, associated with variably cellular fibrous stromal fragments. Intranuclear inclusions, cytoplasmic eosinophilic inclusions, and bile were also noted. FL-HCC showed strong membrano-cytoplasmic CK7 positivity and cytoplasmic granular and canalicular positivity for CD68. In contrast, HCC showed weak focal positivity for CK7 and only canalicular CD68 positivity. Morphometry revealed that FL-HCC cells were 2.19 times the size of HCC.Conclusion:CK7 immunocytochemistry on cell blocks is useful for confirming and distinguishing it from HCC.

Succinate dehydrogenase (SDH)-deficient neoplasia.

The succinate dehydrogenase (SDH) complex is a key respiratory enzyme composed of four subunits: SDHA, SDHB, SDHC and SDHD. Remarkably, immunohistochemistry for SDHB becomes negative whenever there is bi-alleic inactivation of any component of SDH, which is very rare in the absence of syndromic disease. Therefore, loss of SDHB immunohistochemistry serves as a marker of syndromic disease, usually germline mutation of one of the SDH subunits. Tumours which show loss of SDHB expression are termed succinate dehydrogenase-deficient. In addition to loss of SDHB, tumours associated with SDHA mutation also show loss of SDHA expression. Fifteen per cent of pheochromocytoma and paraganglioma (PHEO/PGL) are associated with germline SDH mutation, and therefore SDH-deficient. We recommend screening SDHB immunohistochemistry for all PHEO/PGL. SDH-deficient gastrointestinal stromal tumours (GISTs) show distinctive features, including absent KIT proto-oncogene receptor tyrosine kinase/platelet-derived growth factor receptor A (KIT/PDGFRA) mutations [but positive staining for cKIT and DOG1], virtually exclusive gastric location, lobulated growth, multi-focality, a prognosis not predicted by size and mitotic rate, frequent metastasis to lymph nodes and primary resistance to imatinib therapy. Thirty per cent are associated with SDHA germline mutation and 50% are associated with SDHC epimutation (post-zygotic promoter hypermethylation) - the hallmark of the syndromic but non-hereditary Carney triad (SDH- deficient GIST, SDH-deficient paraganglioma and pulmonary chondroma). SDH-deficient renal carcinoma is newly recognized under the World Health Organization (WHO) 2016 classification and shows vacuolated eosinophilic cytoplasmic and cytoplasmic inclusions. It is particularly associated with SDHB mutation, although SDHC and SDHA mutation occur. SDH-deficient pituitary adenomas are recognized, but appear to be the least common SDH-deficient neoplasm.

Leiomyoma with bizarre nuclei: a morphological, immunohistochemical and molecular analysis of 31 cases

Leiomyomas associated with hereditary leiomyomatosis and renal cell carcinoma syndrome and leiomyomas with bizarre nuclei often show overlapping morphological features, in particular cells with prominent eosinophilic nucleoli, perinucleolar halos, and eosinophilic cytoplasmic inclusions. Although hereditary leiomyomatosis and renal cell carcinoma syndrome is defined by fumarate hydratase (FH) germline mutations, resulting in S-(2-succino)-cysteine (2SC) formation, it is unknown whether leiomyomas with bizarre nuclei show similar alterations. In this study, we evaluated the morphology and FH/2SC immunoprofile of 31 leiomyomas with bizarre nuclei. DNA from tumor and normal tissues from 24 cases was subjected to massively parallel sequencing targeting 410 key cancer genes. Somatic genetic alterations were detected using state-of-the-art bioinformatics algorithms. No patient reported a personal history of renal neoplasia or cutaneous leiomyomas, but one had a family history of renal cell carcinoma while another had a family history of uterine leiomyomas. Aberrant FH/2SC expression was noted in 17 tumors (16 FH-negative/2SC-positive, 1 FH-positive/2SC-positive). On univariate analysis, staghorn vessels, eosinophilic cytoplasmic inclusions, diffuse distribution of prominent eosinophilic nucleoli with perinucleolar halos, and an ‘alveolar pattern of edema’ were associated with an abnormal immunoprofile, but only staghorn vessels remained significant on multivariate analysis. Massively parallel sequencing analysis (n=24) revealed that 13/14 tumors with aberrant FH/2SC immunoprofile harbored somatic FH somatic genetic alterations, including homozygous deletions (n=9), missense mutations coupled with loss of heterozygosity (n=3), and a splice site mutation (n=1), whereas no somatic FH mutations/deletions were found in tumors with normal immunoprofile (n=10; P<0.0001). Leiomyomas with bizarre nuclei with normal FH/2SC staining pattern more frequently harbored TP53 and/or RB1 alterations than those with aberrant FH/2SC immunoprofile (60 vs 14%; P=0.032). These data demonstrate that leiomyomas with bizarre nuclei are morphologically and genetically heterogeneous and that hereditary leiomyomatosis and renal cell carcinoma syndrome-related morphological features, abnormal FH/2SC staining, and somatic FH mutations/deletions can be seen in a subset of sporadic tumors.

Differential Disease Susceptibilities in Experimentally Reptarenavirus-Infected Boa Constrictors and Ball Pythons.

ABSTRACTInclusion body disease (IBD) is an infectious disease originally described in captive snakes. It has traditionally been diagnosed by the presence of large eosinophilic cytoplasmic inclusions and is associated with neurological, gastrointestinal, and lymphoproliferative disorders. Previously, we identified and established a culture system for a novel lineage of arenaviruses isolated from boa constrictors diagnosed with IBD. Although ample circumstantial evidence suggested that these viruses, now known as reptarenaviruses, cause IBD, there has been no formal demonstration of disease causality since their discovery. We therefore conducted a long-term challenge experiment to test the hypothesis that reptarenaviruses cause IBD. We infected boa constrictors and ball pythons by cardiac injection of purified virus. We monitored the progression of viral growth in tissues, blood, and environmental samples. Infection produced dramatically different disease outcomes in snakes of the two species. Ball pythons infected with Golden Gate virus (GoGV) and with another reptarenavirus displayed severe neurological signs within 2 months, and viral replication was detected only in central nervous system tissues. In contrast, GoGV-infected boa constrictors remained free of clinical signs for 2 years, despite high viral loads and the accumulation of large intracellular inclusions in multiple tissues, including the brain. Inflammation was associated with infection in ball pythons but not in boa constrictors. Thus, reptarenavirus infection produces inclusions and inclusion body disease, although inclusions per se are neither necessarily associated with nor required for disease. Although the natural distribution of reptarenaviruses has yet to be described, the different outcomes of infection may reflect differences in geographical origin.IMPORTANCE New DNA sequencing technologies have made it easier than ever to identify the sequences of microorganisms in diseased tissues, i.e., to identify organisms that appear to cause disease, but to be certain that a candidate pathogen actually causes disease, it is necessary to provide additional evidence of causality. We have done this to demonstrate that reptarenaviruses cause inclusion body disease (IBD), a serious transmissible disease of snakes. We infected boa constrictors and ball pythons with purified reptarenavirus. Ball pythons fell ill within 2 months of infection and displayed signs of neurological disease typical of IBD. In contrast, boa constrictors remained healthy over 2 years, despite high levels of virus throughout their bodies. This difference matches previous reports that pythons are more susceptible to IBD than boas and could reflect the possibility that boas are natural hosts of these viruses in the wild.

Atypical teratoid/rhabdoid tumor of lumbar spine in a toddler child.

Atypical teratoid/rhabdoid tumor (AT/RT) is a rare pediatric central nervous system malignancy with poor outcome. AT/RT is infrequently located in the spinal cord. A 16-month-old boy presented with progressive urinary retention and weakness of the lower extremities. Magnetic resonance imaging of the spine revealed an intradural extramedullary mass occupying the spinal canal at the level of T10-L3. The tumor was successfully resected by using neuroendoscopy. Histopathology demonstrated rhabdoid cells with eccentric nuclei and eosinophilic cytoplasmic hyaline inclusions. Immunohistologically, the tumor cells showed positive for epithelial membrane antigen, vimentin and neuron-specific enolase, and negative for integrase interactor 1. After surgery, the patient showed significant improvement in sitting and other neurological signs but presenting with flaccid neurogenic bladder. Intrathecal chemotherapy under European Rhabdoid Registry (EU-RHAB) protocol with Doxorubicin, Carboplatin, Etoposide, Ifosfamide, Vincristine, Cyclophosphamide and Actinomycin-D was given. However, recurrent intradural extramedullary tumor at the level of T11-L2 developed in 3 months. We report a young Asian case of AT/RT in thoracolumbar spine with recurrent tumor shortly after complete surgical resection of the tumor.

Non-H. pylori-Associated Russell Body Gastritis

Case: A 62-year-old woman presented with weakness and rectal bleeding. She was found to be anemic. She denied dysphagia, hematemesis or prior history of gastrointestinal bleeding. She underwent an upper endoscopy that showed mild antral erythema. Biopsies were obtained that showed numerous Mott cells in the lamina propria. These cells have large eosinophilic cytoplasmic inclusions indicating Russell Body Gastritis. Plasma cells, lymphocytes, and neutrophils were also present in the superficial lamina propria. Of note, no Helicobacter pylori bacteria were seen. In situ hybridization kappa and lambda chains showed a polyclonal pattern with a kappa/lambda ratio of 2-3:1. There was no intestinal metaplasia, cellular atypia or evidence of carcinoma. Duodenal biopsies were normal. Discussion: We are reporting this case not only due to the rarity of the diagnosis, but also because in this case of Russell body gastritis, H. Pylori was not identified. A majority of the cases of Russell body gastritis are associated with H. Pylori. Other conditions associated with Russell body gastritis include certain autoimmune conditions like Hashimoto's thyroiditis, rheumatoid arthritis, and also malignancies like MALT lymphoma and plasma cell tumors. Proper identification of Russell Body Gastritis is important for early recognition of these conditions, and also for exclusion of malignancy, which can result in significant reduction in morbidity and mortality.

Immunohistochemistry for 2-Succinocysteine (2SC) and Fumarate Hydratase (FH) in Cutaneous Leiomyomas May Aid in Identification of Patients With HLRCC (Hereditary Leiomyomatosis and Renal Cell Carcinoma Syndrome).

Hereditary leiomyomatosis and renal cell carcinoma syndrome (HLRCC) is caused by germline mutations in the fumarate hydratase (FH) gene and predisposes to cutaneous and uterine leiomyomas and renal cell carcinoma (RCC). HLRCC-associated renal tumors are clinically aggressive, and patients would benefit from surveillance and early detection. Cutaneous leiomyomas that occur in association with HLRCC typically present early and are multiple. Thus far, the presence of certain morphologic features (large eosinophilic macronucleoli surrounded by halos and eosinophilic cytoplasmic inclusions) in RCC and uterine leiomyomas has been shown to correlate with FH mutations. Immunohistochemistry (IHC) for 2-succinocysteine (2SC) and FH has also been shown to correlate well with FH gene mutation status in RCC and uterine leiomyomas. The aim of this study was to assess the effectiveness of morphologic features and IHC at predicting FH gene mutations in cutaneous leiomyomas. We identified 22 patients with multiple cutaneous leiomyomas (40 total MCLs) and 25 patients with single leiomyomas (25 SCLs). Mutations in the FH gene were detected in 11 of 13 (85%) sequenced MCLs and 1 of 11 (9%) SCLs. A strong association was observed between 2SC positivity by IHC and presence of FH gene mutation (P=0.0028 for 2SC) but not with FH loss by IHC (P=0.4 for FH). All 11 MCLs with an FH mutation showed positive staining for 2SC, whereas 6 of 11 showed complete loss of FH staining. Our study suggests that the presence of MCLs should raise the possibility of HLRCC. IHC for FH and 2SC is helpful in detection of FH gene mutations and should be considered in all newly diagnosed cutaneous leiomyomas.

Novel eosinophilic neuronal cytoplasmic inclusions in the external cuneate nucleus of humans.

We report the occurrence of neuronal cytoplasmic inclusions (NCIs) in the external cuneate nucleus of humans. The NCIs appeared as accumulations of eosinophilic rod-like structures in the neuronal somata in 20 (9.5%) of 211 consecutive autopsy cases. Histochemically, the NCIs were stained bright red with Gomori trichrome, Azan-Mallory and methyl green-pyronin, indicating that they contain protein and RNA. Immunohistochemically, the NCIs were positive for stress granule marker proteins, including Hu-antigen R, eukaryotic translation initiation factor 3 and poly(A)-binding protein 1, but negative for ubiquitin- and autophagy-related proteins. Ultrastructurally, the NCIs were composed of randomly oriented arrays of parallel fibrillar crystalline material with a well-defined substructure consisting of longitudinal striations, and were often associated with ribosome-like granules. These NCIs are morphologically, immunohistochemically and topographically distinct from any other inclusions previously described. Their incidence was found to increase with age. A high incidence was also observed in individuals with noninfectious inflammatory disease. These findings suggest that eosinophilic NCIs in the external cuneate nucleus are novel inclusions and might be formed under stress conditions.

The importance of eosinophilic cytoplasmic inclusion bodies in melanocytes as a clue to distinguish between benign and malignant melanocytic lesions

Aim: Since early diagnosis and treatment of melanoma can significantly improve patients' prognosis, discovering new criteria to help differentiate between benign and malignant melanocytic lesions is of significance. In this study we aim to clarify the relationship between the presence of intracytoplasmic eosinophilic inclusion bodies inside melanocytes and the nature of the melanocytic lesion. Methods: Medical records and pathology slides pertaining to 187 patients with melanocytic lesions who had undergone biopsy in Razi Hospital between March 2014 and March 2015 were gathered. Slides were re-examined by a dermatopathologist using a light microscope. Clinical and pathological data were analyzed using SPSS. Results: A total of 196 specimens from 187 patients were studied. The median age of our patients was 42.26 years and 61.5% of them were female while 38.5% were male. The specific eosinophilic intracytoplasmic inclusion bodies were observed in 14 specimens; 8 of which were intradermal nevi and the remaining 6 were from compound nevi. These bodies tended to be present in lesions with congenital features. We found no correlation between age, sex or location of the lesion with the presence of aforementioned bodies. Conclusion: Eosinophilic inclusion bodies present in the cytoplasm of melanocytes are associated with benign melanocytic lesions and are mostly observed in cells with abundant vacuolated cytoplasm and in lesions with congenital features. Therefore these bodies can be helpful in diagnosing benign and longstanding lesions and differentiating them from malignancies.

Isolation and detection of avian nephritis virus by RT-PCR from commercial broiler flocks affected with visceral gout in India

The present study reports pathomorphology, isolation and detection of Avian Nephritis Virus (ANV) by RT-PCR from a field outbreak in commercial broiler in Raipur, Chhattisgarh. Clinical signs and age wise mortality were recorded and detailed post mortem examination were performed in died chicks. The kidney tissues were collected for histopathology and isolation of virus. Clarified suspensions (10% w/v) of homogenate were prepared and inoculated into allantoic cavity of 11 day old embryonated SPF eggs. After three passages the embryos were examined for any lesions and the collected tissue samples were used for RNA extraction. The mortality was ranged from 3 to 8% in different affected flocks with 6% average mortality. During post mortem examination, the major gross lesions were renal damage and visceral uricosis. The kidneys were pale and enlarged with dilated ureters indicated acute tubular nephrosis. Microscopically moderate, multifocal, peri glomerular and interstitial mononuclear cells infiltration were the most prominent lesions. Cytoplasmic eosinophilic inclusion bodies were found in necrotized epithelial cells and desquamated tubular epithelial cells. After three passages, three embryos revealed pale swollen kidneys with full of chalky deposits and dilatation of ureters. For RT-PCR, RNA extract from pooled kidney samples of five embryos were processed. The visualization by agarose gel electrophoresis showed a product of expected size of 325 bp Avian Nephritis Virus (ANV) specific product. The RT-PCR used in the present study can be a potential tool for routine diagnosis of samples submitted from cases of gout and nephropathy in chickens.

Review of renal cell carcinoma with rhabdoid features with focus on clinical and pathobiological aspects.

Rhabdoid morphology in renal cell carcinoma (RCC) may, like sarcomatoid change, be perceived as a type of dedifferentiation, and is a poor prognostic factor. Histologically, rhabdoid neoplastic cells are round to polygonal cells with globular eosinophilic cytoplasmic inclusions and eccentric vesicular nuclei and enlarged nucleoli. All types of RCC, including clear cell, papillary, chromophobe, collecting duct carcinoma, renal medullary carcinoma, acquired cystic disease-associated RCC, ALK-positive renal cancer and unclassified RCC, may display a variably prominent rhabdoid phenotype. Immunohistochemically, the cytoplasm of rhabdoid cells shows positivity for vimentin and/or cytokeratin. Ultrastructurally, cytoplasmic whorls/aggregates of intermediate filaments correspond to light microscopically observed inclusions. Genetically, a previous report suggests that combined loss of BAP1 and PBRM1 may be associated with rhabdoid morphology. As with sarcomatoid change, pathologists should describe, estimate and state the proportion of tumor cells with a rhabdoid phenotype in the routine pathology report of RCC.

Bunina bodies in motor and non‐motor neurons revisited: A pathological study of anALSpatient after long‐term survival on a respirator

Bunina bodies (BBs) are small eosinophilic neuronal cytoplasmic inclusions (NCIs) found in the remaining lower motor neurons (LMNs) of patients with sporadic amyotrophic lateral sclerosis (SALS), being a specific feature of the cellular pathology. We examined a case of SALS, unassociated with TDP-43 or C9ORF72 mutation, of 12 years duration in a 75-year-old man, who had received artificial respiratory support for 9 years, and showed widespread multisystem degeneration with TDP-43 pathology. Interestingly, in this patient, many NCIs reminiscent of BBs were observed in the oculomotor nucleus, medullary reticular formation and cerebellar dentate nucleus. As BBs in the cerebellar dentate nucleus have not been previously described, we performed ultrastructural and immunohistochemical studies of these NCIs to gain further insight into the nature of BBs. In each region, the ultrastructural features of these NCIs were shown to be identical to those of BBs previously described in LMNs. These three regions and the relatively well preserved sacral anterior horns (S1 and S2) and facial motor nucleus were immunostained with antibodies against cystatin C (CC) and TDP-43. Importantly, it was revealed that BBs exhibiting immunoreactivity for CC were a feature of LMNs, but not of non-motor neurons, and that in the cerebellar dentate nucleus, the ratio of neurons with BBs and TDP-43 inclusions/neurons with BBs was significantly lower than in other regions. These findings suggest that the occurrence of BBs with CC immunoreactivity is intrinsically associated with the particular cellular properties of LMNs, and that the mechanism responsible for the formation of BBs is distinct from that for TDP-43 inclusions.

Study on the etiology of fibropapillomatosis of olive ridley sea turtles (&lt;i&gt;Lepidochelys olivacea&lt;/i&gt;) nesting in the National Wildlife Refuge at Ostional, Guanacaste, Costa Rica

Sea turtle fibropapillomatosis is an emerging disease characterized by a proliferation of cutaneous papillomas, fibromas, and fibropapillomas and occasional visceral fibromas. This paper aims to contribute tothe etiology of fibropapillomatosis in olive ridley sea turtles (Lepidochelys olivacea) nesting in OstionalNational Wildlife Refuge. Twenty six olive ridley turtles with cutaneous fibropapilloma were sampled and24 healthy olive ridley turtles served as controls. Biopsies were taken of the cutaneous tumors in sick seaturtles, as well as skin biopsies from control subjects, and blood samples were collected from all turtles.Tumorous samples and skin samples were microscopically analyzed in order to differentiate the histologicalfactors resulting from the disease pathogenesis, where the main histological findings were papillaryepidermal hyperplasia, orthokeratotic hyperkeratosis, spirorchid-like eggs in the dermis, and eosinophilic cytoplasmic inclusion. Hematology and blood chemistry studies were conducted on blood samples, andMCHC, heterophils, lymphocytes, monocytes, AST, total protein, albumin and globulin values were significantlydifferent between healthy turtles and turtles with tumors. A PCR test was also conducted in thesamples to determine the presence of herpesvirus and papillomavirus as possible etiologic agents, wherethe papilomavirus was absent in all the samples, while the herpesvirus was present in 69.23% of the tumors,this being the most probable etiological agent of fibropapillomatosis.La fibropapilomatosis de la tortuga marina es una enfermedad emergente caracterizada por múltiples papilomas, fibromas y fibropapilomas cutáneos, así como ocasionales fibromas viscerales. El presente trabajo tiene como objetivo contribuir a la etiología de la fibropapilomatosis en la tortuga lora (Lepidochelys olivacea) que anida en el Refugio Nacional de Vida Silvestre Ostional. Se muestrearon 26 tortugas lora con fibropapilomas cutáneos y 24 tortugas lora sanas que sirvieron de control. Se tomaron biopsias excisionales de los tumores cutáneos de las tortugas enfermas y biopsias de piel de las tortugas control, además se recolectaron muestras de sangre de todas las tortugas. Las muestras tumorales y de piel se analizaron microscópicamente para diferenciar los factores histológicos que resultan de la patogénesis de la enfermedad, donde los hallazgos histopatológicos principales en los fibropapilomas fueron: crecimiento papiliforme, hiperqueratosis ortoqueratótica, huevos de parásitos similares a espiróquidos en la capa dérmica e inclusión eosinofílica citoplasmática. A las muestras de sangre se les realizó análisis hematológico y de química sanguínea, donde los valores de CHCM, heterófilos, linfocitos, monocitos, AST, proteínas totales, albúmina y globulinas resultaron significativamente diferentes entre las tortugas sanas y las tortugas con tumores. Se realizó PCR a las muestras para determinar la presencia de genoma de herpesvirus y papilomavirus como posibles agentes etiológicos, donde el papilomavirus estuvo ausente en la totalidad de las muestras, mientras el virus Herpes se presentó en el 69.23% de los tumores posicionándose como el posible agente etiológico de la enfermedad.

Metastatic Malignant Extra-renal Rhabdoid Tumor (MERT) of the Esophagus

Purpose: We report a 61-year-old female who presented with a 5-month history of intermittent dysphagia to solids and an 8-pound weight loss. She underwent a barium swallow that revealed a partially obstructing distal esophageal lesion suspicious for malignancy. She was referred to an outside gastroenterologist for an upper endoscopy (EGD). EGD demonstrated a large, partially obstructing fungating mass in the esophagus from 33 cm to 40 cm. Cold forceps biopsies were performed revealing poorly differentiated non-small cell carcinoma. Immunohistochemistry (IHC) staining was performed for epithelial markers and was positive for epithelial membrane antigen (EMA), cytokeratin AE1/3, and CAM 5.2. The impression was that of an esophageal non-small cell carcinoma. Staging CT scan of the chest, abdomen, and pelvis showed marked concentric wall thickening of the distal esophagus with extensive mediastinal lymphadenopathy and porta caval/hepatis lymph nodes. Subsequent PET scan demonstrated uptake in the distal esophagus and adjacent lymph nodes. She was then referred to us for staging via endoscopic ultrasound (EUS). EUS revealed the partially obstructing fungating mass in the distal esophagus with poorly defined borders and evidence of extension beyond the adventitia. Malignant appearing lymph nodes were seen in the paraesophageal region, gastrohepatic ligament, and the celiac axis. The left adrenal gland also appeared enlarged. EUS-guided fine needle aspiration (EUS-FNA) was performed of a celiac lymph node and the left adrenal gland. Immediate cytological evaluation (ICE) of the celiac lymph node aspirate was positive for malignant cells. Cell block of the celiac lymph node revealed large, poorly cohesive cells with vesicular chromatin, eccentric nuclei with prominent nucleoli, and dense eosinophilic cytoplasmic inclusions. IHC staining for vimentin was performed and was positive; this confirmed a diagnosis of metastatic malignant rhabdoid tumor. Recuts of the outside slides also stained positive for vimentin-consistent with malignant extra-renal rhabdoid tumor (MERT) of the esophagus. MERT of the esophagus is rare and carries a poor prognosis with a 1-year survival of approximately 30%. MERT is defined by the presence of large, poorly cohesive cells with vesicular chromatin, eccentric nuclei with prominent nucleoli, and eosinophilic cytoplasmic inclusions. Co-expression of vimentin and epithelial cytokeratin can assist in confirming the diagnosis. Our patient with metastatic MERT was subsequently referred to an oncologist for chemotherapy (cisplatin and 5-fluorouracil). This rare case demonstrates the importance of maintaining a high suspicion of MERT in patients with esophageal non-small cell carcinoma.

Malignant Extra-renal Rhabdoid Tumor (MERT) of the Gastrointestinal Tract: A Systematic Review

Purpose: A 61-year-old female presented to us with metastatic Malignant Extra-renal Rhabdoid Tumor (MERT) of the gastrointestinal tract, which prompted us to conduct a systematic review of the literature. MERT is a rare entity that carries a poor prognosis due to its features of early metastasis and rapid growth. Methods: A systematic search and review of the literature was performed (1966-2013) utilizing MED-LINE (Pubmed), Cochrane Library, and a review of references within review articles. The search was not restricted by date or language. Only cases of rhabdoid tumor of the gastrointestinal tract in adults were included. Results: Our search resulted 19 published cases of MERT of the gastrointestinal tract reported between 1993 to 2005: seven gastric, five esophageal, four small intestinal and three colonic. The mean age of presentation was 63 years (range 52-84). The gender distribution was 74% male (14/19) and 26% female (5/19). The mean tumor size as measured on post-operative pathology was 8.8 cm (range 3.8 cm-16 cm). On gross examination, MERT can appear fungating or ulcerated with hemorrhagic necrosis. The characteristic histology of rhabdoid tumor reveals large, poorly cohesive cells with vesicular chromatin, eccentric nuclei with prominent nucleoli, and dense eosinophilic cytoplasmic inclusions. Immunohistochemical (IHC) staining was used in 100% (19/19) of patients to confirm a diagnosis. MERT stains positive for vimentin and cytokeratin- although other epithelial markers such as Neuron Specific Enolase (NSE) and Epithelial Membrane Antigen (EMA) can also be utilized. In our review, 100% of (19/19) tumors were positive for vimentin, 95% (18/19) were positive for cytokeratin or EMA, and 5% (1/19) were positive for NSE. Forty-seven percent (9/19) of patients had local lymph node metastases and 53% (10/19) had distant metastases at presentation. Eighty-four percent (16/19) of patients had a surgical resection, 5% (1/19) underwent radiation therapy and 5% (1/19) underwent chemotherapy. Sixteen percent (3/19) either died before treatment could be initiated or had no treatment information available. Sixty-eight percent (13/19) of patients died within 1 year of diagnosis, and 16% (3/19) were alive at 1-year follow up. Follow up information was not available for 16% (3/19) of patients. The mainstay of treatment remains surgical resection with limited literature on the use of chemotherapy or radiation therapy. Conclusion: MERT is a rare entity that carries a poor prognosis with a high mortality rate. As such, it is an important entity to consider as it requires IHC staining to confirm the diagnosis.

Unusual Manifestation of Molluscum Contagiosum: Eruptive Papules on the Face and Neck of an Immunocompetent Patient

Dear Editor: Molluscum contagiosum (MC) is a common benign skin disease caused by the pox virus and usually affects young children. Most MC in adults occurs in people with an immunosuppressive status, but it can also appear in immunocompetent adults who have experienced friction or scrubbing. We herein report a case of MC that presents multiple pinhead-sized eruptive skin-coloured papules covering the whole face and neck in a patient without a history of epidermal trauma. A 60-year-old Korean woman with a history of recent onset diabetes presented to our clinic with sudden eruptive papules on her face and neck, which had been persistent for the past 6 months. She had been treated with topical hydrocortisone in the local clinic, but no improvements were observed. Even though she was mostly asymptomatic, the patient complained of occasional mild pruritus. She had no history of towel scrubbing or massage. Upon physical examination, multiple 2 to 3-mm-sized skin-coloured papules were observed on her face and neck (Fig. 1). Fig. 1 (A) Multiple 2- to 3-mm-sized skin-coloured papules observed on the face and neck. (B) Close up view of the skin-coloured papules. Keratin-like material was observed after extractions of some lesions, resulting in the performance of punch biopsy under the initial impression of milium. Histopathologic examination revealed epidermal cells bearing large eosinophilic cytoplasmic inclusion bodies, typical of the molluscum body, and the lesion was diagnosed as MC (Fig. 2). Due to diffuse distributions across the face and neck, imiquimod cream, oral gamma linolenic acid 360 mg and oral cimetidine 2,000 mg were used daily for 3 months, until all the lesions were resolved. We believe that the immunomodulating effects from imiquimod cream and oral cimetidine could have contributed to the resolution. Fig. 2 Epidermal cells bearing large eosinophilic cytoplasmic inclusion bodies, typical of the molluscum body (H&E, ×100). There have been several reports of disseminated molluscum contagiosum in patients with hematologic malignancies, human immunodeficiency (HIV) infection, or in patients taking immunosuppresants such as methotrexate or azathioprine1,2. Cases associated with traumas and contacts have also been reported, such as molluscum folliculitis after shaving or molluscum developed after use of a nylon towel at a public spa3,4. In this case, the patient was a healthy woman without any evidence of systemic diseases other than diabetes and was not taking any medicine that could impair cellular immunity. Lab data including complete blood counts and routine chemistry were within normal values and venereal disease research laboratory (VDRL) was non-reactive. Anti-HIV antibodies were also negative. In addition, she had no history of shaving, friction or massage, which might cause the inoculation of pox virus from epidermal trauma. However, an incidental MC infection could have spread to her whole face and neck due to the application of hydrocortisone cream after a misdiagnosis. In conclusion, our case suggests that dermatologists should perceive various clinical features of MCs in order to avoid misdiagnosis due to unusual clinical features. Additionally, the diagnosis of mollosum contagiosum should not be excluded, even if the patient is a healthy person without immunodeficiency.