Immunoreactivity For Cytokeratin Research Articles

Ciliary body myxoid epithelioid sarcoma in a cat: a case report

BackgroundThe majority of primary, intraocular tumors in cats originate from the uvea and include feline diffuse iris melanoma, lymphoma, and iridociliary epithelial adenoma or adenocarcinoma. In this case report, we describe for the first time the clinical, histological, and immunohistochemical findings of a rare myxoid intraocular neoplasm arising from the ciliary body in a cat.Case presentationA 14-year-old, female, spayed domestic shorthaired cat was presented for evaluation of discolouration of the right eye. Upon examination, a clear to light whitish-tan, bubble-shaped intraocular mass adherent to the inferior ciliary body and extending into the anterior chamber was noted. Within five weeks, the tumor was significantly larger and the eye had developed secondary glaucoma so was enucleated. Light microscopic examination of the globe revealed a multinodular, hypocellular neoplasm arising from the ciliary body composed of interwoven spindle cells embedded in abundant amounts of a lightly basophilic myxoid matrix. Neoplastic cells exhibited strong immunoreactivity for cytokeratin while also showing moderate to strong immunoreactivity to vimentin. A diagnosis was therefore made of an unusual intraocular myxoid epithelioid sarcoma arising from the ciliary body.ConclusionsAlthough apparently exceedingly rare, epithelioid myxosarcoma should be included as a differential diagnosis for intraocular tumors in cats and they represent a clinical, histologic, and immunohistochemical diagnostic challenge. Early surgical intervention should be considered to prevent local invasion and ascension to the brain.

Esophageal carcinoma with SMARCA4 mutation: a narrative review for this rare entity.

Esophageal carcinoma with switch/sucrose nonfermenting (SWI/SNF)-related, matrix-associated, actin-dependent regulator of chromatin, subfamily A, member 4 (SMARCA4) mutation is a rare variant of malignant esophageal epithelial neoplasm, which is characterized by the loss of SMARCA4/BRG1 protein on immunohistochemistry or alterations in the SMARCA4 gene on sequencing. Only a few case series and case reports of esophageal carcinoma with SMARCA4 mutations have been published in the English literature; the rarity of the disease poses significant diagnostic challenges for surgical pathologists and could potentially lead to delayed or suboptimal patient care. Herein, we reviewed the available literature on esophageal carcinoma with SMARCA4 mutations to discuss its epidemiology, clinical presentation, pathological and molecular features, diagnostic challenges, treatment, and prognosis. The PubMed, Scopus, Ovid, and Google Scholar databases were extensively reviewed. The references included in the articles were cross-examined to identify any missing articles. We searched for all published literature on esophageal carcinoma with SMARCA4 mutations from inception of the databases to date. Esophageal carcinoma with SMARCA4 mutations is most common in middle-aged and older men. Barrett esophagus and gastroesophageal reflux disease (GERD) are the most associated risk factors. Dysphagia was the most common initial clinical presentation. Esophagogastroduodenoscopy (EGD) is the preferred diagnostic modality. Microscopically, the tumor cells exhibited epithelioid features mixed with variable components of rhabdoid and glandular differentiation. The tumor cells showed variable immunoreactivity for cytokeratin and sometimes weakly expressed neuroendocrine or B-lymphocyte markers (Pax5), which are potential diagnostic pitfalls. Melanoma marker tests showed negative results. The SMARCB1/INI1 protein remains intact, and a definitive diagnosis necessitates the presence of either SMARCA4/BRG1 protein loss or SMARCA4 gene mutations. Esophageal carcinoma with SMARCA4 mutations shows overly aggressive behavior and presents with advanced stages of disease; most patients succumb to the disease within 1 year of initial diagnosis. Esophageal carcinoma with SMARCA4 mutation is an overly aggressive disease, and further research on the affected molecular pathway may help improve its prognosis.

Histological and immunohistochemical features of carcinomas with pulmonary involvement in cattle.

Primary pulmonary neoplasms in cattle are rare. There are few studies on the pathological findings of these neoplasms in this species. This study aimed to describe the histological and immunohistochemical findings of primary and metastatic pulmonary carcinomas in cattle. We conducted a retrospective study of 19 cases of epithelial neoplasms with pulmonary involvement. Histologically, most of the neoplasms were classified as primary pulmonary neoplasms, including different adenocarcinoma subtypes (4/19, 21%) and adenosquamous carcinomas (3/19, 16%), followed by squamous cell carcinoma (6/19, 32%), metastatic uterine adenocarcinoma (4/19, 21%), metastatic hepatocellular carcinoma (1/19, 5%), and metastatic cholangiocarcinoma (1/19, 5%). By immunohistochemistry, all neoplasms were positive for pancytokeratin, and 4/19 (21%) were positive for vimentin. Primary pulmonary neoplasms had immunoreactivity for thyroid transcription factor-1 (6/7), while only 2 of these cases were positive for napsin A. All cases with squamous differentiation (9/9) had immunoreactivity for cytokeratin (CK) 5/6, while only 7 of these cases were positive for p40. CK20, CK7, and CK8/18 showed varied immunoreactivity in the primary and metastatic pulmonary carcinomas but were important markers to confirm the diagnosis of primary mucinous adenocarcinoma and metastatic cholangiocarcinoma. HepPar-1 was only positive in the metastatic hepatocellular carcinoma. The limited number of cases of metastatic uterine adenocarcinomas in this study precluded identification of a specific immunophenotype for this tumor. Immunohistochemistry proved to be an important tool to confirm the proper classification of these neoplasms.

Intraparotid Ganglioneuroma: A rare case report.

Introduction: Ganglioneuromas (GNs) are slow-growing, benign tumors arising from Schwann cells, gangliocytes, and neuronal tissues. Case Presentation: We report a rare intraparotid ganglioneuroma in a 42-year-old female presented with a parotid mass. The onset of the lesion dated back to 2021, but the growth was remarkable only in November 2022. The FNA suggested a plexiform neurofibroma. The post-surgical microscopic examination of the excised lesion revealed neoplastic large, rounded cells with abundant, finely granular eosinophilic cytoplasm and a large, eccentric nucleus with a prominent nucleolus as well as fasciculated, with an elongated cytoplasm with fine fibrillar extensions. No mitosis or tumor necrosis was observed. The periphery of the tumor showed perineural entrapment. The immunohistochemical staining for S100 protein, synaptophysin, and chromogranin A were positive. However, the neoplastic cells showed no immunoreactivity for cytokeratin (CK5/6, CK7, AE1/AE3), epithelial membrane antigen, HMB45, Melan A, CD30, CD117 and p40. The case was signed out as mature intraparotid ganglioneuroma. Conclusion: The treatment of choice was surgical resection without adjuvant radiotherapy. No recurrence or post-surgical complications were hitherto reported. To the best of our knowledge, this is the first reported case of intraparotid ganglioneuroma. Caution should be taken not to diagnose this benign neoplasm as a metastasis (e.g. metastatic neuroblastoma) or to request unnecessary overtreatment (e.g., postoperative chemotherapy and radiotherapy).

Usefulness and Limitations of Cryopreservation for Immunocytochemical Staining of Canine Cytological Specimens for Detection of Cytokeratin and Vimentin.

Immunocytochemistry is an advanced diagnostic tool for identifying the origin of tumor cells. This study aimed to highlight the usefulness of cryopreserved, air-dried cytological samples in detecting cytokeratin and vimentin. Air-dried cytological smear samples were prepared from a total of 39 resected canine tumors and stored in a medical freezer without fixation. The duration of cryopreservation ranged from 2 to 56 months. The same tumors were processed for routine histopathological examination. Based on the morphological diagnosis, cryopreserved FNA smears from epithelial tumors were stained by enzymatic immunocytochemistry (ICC) for cytokeratin; those from mesenchymal and melanocytic tumors were stained by ICC for vimentin. To ascertain the positivity of tumor cells to the selected markers, tissue paraffin-embedded sections were also stained by immunohistochemistry (IHC) for the same markers. Immunoreactivity for cytokeratin was detected in cryopreserved cytological smears for a maximum of 46 months. Immunoreactivity for vimentin was clearly detected for 33 months. Smears stored at room temperature for 1 week did not show any signals under immunocytochemical examination. Thus, immunocytochemistry for cytokeratin and vimentin can be safely applied to air-dried smears cryopreserved in a freezer for at least 33 months.

Xanthomatous Giant Cell Renal Cell Carcinoma: Another Morphologic Form of TSC -associated Renal Cell Carcinoma.

Over the past decade, several distinct novel renal epithelial neoplasms driven by underlying tuberous sclerosis comples ( TSC)/ mammalian target of rapamycin (MTOR) pathway mutations have been described. We report herein two distinctive TSC2 -mutated renal cell carcinomas which do not fit any previously described entity. The two renal carcinomas occurred in young patients (ages 10 and 31y), and were characterized by highly permeative growth within the kidney with metastases to perirenal lymph nodes. The neoplastic cells were predominantly large, multinucleated giant cells having variably eosinophilic to xanthomatous cytoplasm with basophilic stippling and frequent vacuolization. While the discohesive nature of the neoplastic cells, xanthomatous cytoplasm, immunoreactivity for histiocytic markers and minimal immunoreactivity for conventional epithelial markers raised the possibility of a histiocytic neoplasm, multifocal immunoreactivity for cytokeratin 20 helped establish their epithelial nature. Despite the aggressive growth pattern of these neoplasms and lymph node metastases, mitotic figures were rare and Ki-67 indices were low (<1%). One patient with follow-up shows no evidence of disease seven years after nephrectomy with no adjuvant therapy. Next-generation sequencing demonstrated TSC2 mutations in each case. By immunohistochemistry, downstream markers of mTOR pathway activation S6K1, 4EBP1, and glycoprotein nonmetastatic melanoma protein B were all highly expressed in these neoplasms, suggesting mTOR pathway activation as the neoplastic driver. While the cytokeratin 20 immunoreactivity and focal basophilic cytoplasmic stippling suggest a relationship to eosinophilic solid and cystic renal cell carcinoma, and cytoplasmic vacuolization suggests a relationship to eosinophilic vacuolated tumor, these neoplasms appear to be distinctive given their permeative growth patterns and predominant xanthomatous giant cell morphology. Addition of cytokeratin 20 to a panel of epithelial markers helps avoid misdiagnosis in such cases.

Augmented Expression of NOGO-A and Its Receptors in Human Retinal Pigment Epithelial Cells Following Treatment with Human Amniotic Fluid.

Background:Nogo-A, a myelin-associated inhibitor for neurite outgrowth, has important role in visual system development. Trans-differentiation ability of human amniotic fluid (HAF) on human retinal pigment epithelial cells (hRPEs) towards neural progenitor cells has been observed in several studies. We aimed to investigate the expression of NOGO-A gene and its receptors as a marker of neural differentiation in HAF-treated hRPE cells.Methods:hRPE cells were cultivated and immune characterized via RPE65 and cytokeratin 8/18 protein markers. Also, the cytotoxicity effect of 30% HAF on hRPE cells was evaluated using ELISA cell death assay. Finally, expression of NOGO-A and its receptors, RTN4R and LINGO1 was evaluated in the cells treated with HAF in comparison with FBS-treated cells using quantitative real-time PCR.Results:Harvested cells showed immunoreactivity for cytokeratin 8/18 and RPE65, confirming the hRPE cell identity. Besides, HAF had no cytotoxic effect on hRPE cells compared with FBS-treated cells. Results showed that NOGO-A and its receptors were expressed in cultured hRPE cells. Besides, comparative gene expression analysis revealed significant increased expression of the investigated genes in HAF-treated hRPE cells compared to FBS-treated cells.Conclusion:Augmented expression of NOGO-A and its receptors can support neural differentiation of hRPE when the cells are treated with HAF. Our outcomes provide more evidences on the trans-differentiation ability of HAF on hRPE cells into neural progenitors and retinal neural cells, but further studies are needed to elucidate the exact mechanism.

Pathological and Immunohistochemical Microscopy of Natural Cases of Canine and Feline Neoplastic Mammary Lesions.

Mammary cancer is the second most common tumor worldwide. Small animal mammary neoplasms provide an outstanding model to study cancer in humans, as tumors in both share a similar environment, histopathologic features, and biological behavior. This study aims to investigate the percentage and microscopy of breast tumors in affected dogs and cats; its relationship to breed, age, and sex; and the immunohistochemical expression of estrogen receptor (ER), progesterone receptor (PR), Ki-67, and cytokeratin 8. Twenty-four females (12 dogs and 12 cats) and one male were examined from February 2018 to February 2020. The highest percentage of mammary neoplasia from the highest to the lowest manifested as tubular carcinoma, leiomyosarcoma, fibroadenoma, and cystic papillary carcinoma. The current study reported the second micropapillary invasive carcinoma in a male cat and the third lipid-rich carcinoma in a female cat. Although tubular carcinoma was the most common mammary neoplasm in cats, leiomyosarcoma was the most common in dogs. The immunohistochemical staining revealed diffuse and intense cytoplasmic immunoreactivity for cytokeratin 8 in lipid-rich carcinomas. However, moderate expression of ER in benign tumors and slight to moderate ER expression in malignant mammary lesions were reported. On the contrary, there was a negative PR expression in benign lesion. It could be concluded that a close relationship between ER expression and nuclear antigen Ki-67 was found.

Immunohistochemical expression of PAX8, PAX2, and cytokeratin in melanomas.

Deviations from the classic melanocytic immunophenotype in melanoma can present a diagnostic challenge. PAX8 and PAX2 are common markers for renal or Müllerian differentiation. While most PAX8+ or PAX2+ carcinomas are seldom confused with melanoma, some cases may show a more ambiguous immunophenotype, especially when MiTF family altered renal cell carcinoma (MiTF-RCC) is in the differential diagnosis. Neither PAX8 nor PAX2 expression has been reported in melanoma to date. We aimed to better characterize PAX8, PAX2, and cytokeratin immunoreactivity in a large series of melanomas. Tissue microarrays consisting of 263 melanomas were immunostained for PAX8, PAX2, and cytokeratin and graded by an h-score. PAX8 expression was seen in 7.9% of melanomas and was significantly associated with spindle cytomorphology. PAX2 was positive in one (0.4%) melanoma. Cytokeratin positivity was seen in three (1.2%) cases and was associated with metastases. PAX8 is expressed in a subset of melanomas and may be strong/extensive. As PAX8 positivity does not exclude a diagnosis of melanoma, it should be used in conjunction with other immunohistochemical markers, such as cytokeratin and PAX2, when melanoma, MiTF-RCC, and other PAX8+ tumors are in the differential diagnosis.

Comparative In Vitro and In Vivo Studies on Feline, Canine, and Human Merkel Cell Carcinoma.

Merkel cell carcinoma (MCC) is an aggressive cutaneous neuroendocrine tumor, and most human MCC cases are infected by Merkel cell polyomavirus (MCPyV). However, the underlying pathogeneses of MCC in animals remain unclear. In the present study, newly established cell lines from feline and canine MCC, a MCPyV-positive human MCC cell line, and MCC tissues from 25 cats and 1 dog were examined and compared pathologically. Feline and canine MCCs were composed of tumor cells arranged in trabeculae and solid packets. Twenty out of 25 feline MCC cases (80%) had other proliferative cutaneous lesions, such as carcinoma in situ and squamous cell carcinoma. Among the 25 feline MCC cases, tumor cells were immunopositive for cytokeratins (CKs), including CK5/6 (4/25 cases, 16%), CK7 (5, 20%), CK18 (25, 100%), CK19 (20, 80%), and CK20 (20, 80%). The tumor cells of feline MCC were also immunopositive for synaptophysin (24/25, 96%) and CD56 (22/25, 88%). The tumor cells of canine MCC were immunopositive for CK18, CK19, CK20, and synaptophysin. Cultured feline and canine MCC cells grew in adherent monolayers and exhibited diffuse cytoplasmic immunoreactivity for CKs, whereas human MCC cells grew in suspension and exhibited dot-like cytoplasmic immunoreactivity for CKs. Differences in the distribution of CKs between human and animal MCC may be attributed to cell adhesion propensities. MCPyV genes and antigen were not detected in feline or canine MCC, suggesting a different etiology from human MCC.

Seasonal morphology and immunoreactivity of cytokeratin and atrial natriuretic peptide in dromedary camel poll glands.

Poll glands are characteristic feature of dromedary camels; although they yield a yellowish offensive secretion, especially during rutting (breeding) season, their function is not yet exactly specified. The present study shows the seasonal morphology and immunoreactivity of cytokeratin (CK) and atrial natriuretic peptide (ANP) in the camel poll gland; the result could clearly specify the role of the gland in camel reproduction. Poll glands are compound tubulo-alveolar in structure. During rutting season, the secretory units showed wide lumina and simple squamous epithelium surrounded by myoepithelial cells; the lumina became narrower and the epithelium changed to simple cuboidal during non-rutting season. Many glandular lobules showed abundant interlobular connective tissue with fewer and smaller secretory units during non-rutting season compared to rutting season. Positive CK and ANP immunoreactivity was detected in the cytoplasm of epithelial cells of secretory units and ducts together with the myoepithelial cells and blood vessels. Although CK immunoreactivity was more intense during rutting season in comparison to non-rutting season, there was no seasonal variation in ANP immunoreactivity. During both seasons, while the glandular capsule, connective tissue septa, interstitium showed negative CK immunoreactions, they reacted moderately to ANP. In conclusion, the poll gland undergoes annual structural and functional changes which are suggested to correlate with the male seasonal sexual behaviour. Further, the biological role of CK and ANP proteins together with their immunohistochemical expression in the camel poll gland suggests a stimulatory effect in the glandular secretory cells, and hence, they might modify camel sexual activity.

Adamantinoma-like Ewing Sarcoma of the thyroid gland: Cytomorphologic, phenotypic and molecular features.

Adamantinoma-like Ewing Sarcoma (ALES) is a rare subtype of Ewing sarcoma family of tumors (EFTs) which are defined by their EWSR1 gene rearrangements. We present a case of a 15-year old female with a swelling in her anterior neck of 4 months duration which had recently begun to rapidly grow in size. Fine needle aspiration showed a small blue round cell tumor with immunoreactivity for cytokeratin, CD99 and FLI1. Material for molecular testing was available on the resection specimen. Demonstration of t(11;22) (EWS-FLI1) was helpful in establishing the diagnosis.

Carcinoma with Vertebral Column Metastasis in Two Dogs

Background: Carcinomas are aggressive and invasive malignancies that originate from any type of epithelial cell and are responsible for many deaths in dogs. Carcinoma metastases occur primarily via the lymphatic route; however, they can occur by blood flow, thus reaching bone structures. In dogs, metastasis of mammary and squamous cell carcinomas to the skeletal system is poorly described. The aim of this study was to report two cases of dogs that developed metastases of carcinomas to the vertebral column.Cases: Case 1. A 10 years-old, male, mixed-breed dog with paralysis of the left pelvic limb, subcutaneous mass in the lumbar region, apathy, anorexia and progressive weight loss and with a previous history of amputation of the right pelvic limb resulting from squamous cell carcinoma (SCC) in the integument of the cranial face of the femorotibiopatellar joint. Due to the patient's clinical condition and the negative prognosis associated with the neoplasia, euthanasia was performed. At necropsy, infiltrating the lumbar vertebrae from L5 to L7, a whitish and firm mass of approximately 15 x 8 cm was observed. Histologically, it comprised a malignant epithelial neoplastic development consisting of nests and cords interspersed with fibrovascular stroma, containing multiple keratine pearls. There was moderate to severe anisocytosis, severe anisokariosis, and about 4 mitosis figures for every 10 high power fields (400x). The histological features were consistent with an invasive SCC. Anti-cytokeratin and anti-p63 immunohistochemical (IHC) evaluations were performed, both with immunoreactivity in neoplastic cells. Case 2. An 8 years-old, female, Chihuahua with bilateral paralysis of the pelvic limbs, anorexia, and progressive weight loss, with a history of excision of solid mammary carcinoma. The clinical condition evolved to the absence of deep pain in all limbs and fecal and urinary retention, opting for euthanasia. At necropsy, a nodule between T3 and T4 was observed, yellowish-white and firm, measuring about 5 x 3.8 cm, invading the spinal canal, and compressing the spinal cord. Histologically, it comprised malignant epithelial neoplasia infiltrating intervertebral ligaments, musculature, and vertebrae of the thoracic spine, organized in a dense mantle of polygonal to rounded cells, delimited in lobes by abundant fibrovascular tissue. Moderate anisokaryosis and accentuated anisocytosis were observed and about 6 mitosis figures for every 10 high power fields (400x). The histological characteristics of the tumor were compatible with metastasis due to grade II solid mammary carcinoma. Immunohistochemical evaluations of anti-cytokeratin, anti-c-erbB2, and anti-estrogen and progesterone receptors were performed, with immunoreactivity for cytokeratin and c-erbB2 in neoplastic cells.Discussion: There are no current data indicating which tumors that metastasize most frequently to the vertebral column. In the reported cases, it was found that the clinical signs presented by the animals are directly associated with the compression of specific areas of the spinal cord, as well as bone pain, resulting from tumor expansion and degeneration of the bone matrix, similar to what has been reported previously. The immunohistochemical diagnosis of anti-p63 in case 1 and anti-oncoprotein C-erbB2 in case 2, were essential to determine the neoplastic origin in the absence of the primary tumor. Despite being a place of low incidence of metastases, bones have a physiologically favorable environment for the implantation of neoplastic cells, especially when there is bone marrow involvement. Because of this and despite the rare occurrence, metastasis of carcinomas to the vertebral column should always be considered as differential diagnoses in patients presenting with clinical signs compatible with spinal cord compression and a history of previous neoplasia.

Chronic Inflammatory and Proliferative Lesions of the Gallbladder in Aged Pigs.

Primary epithelial tumors of the gallbladder are rarely reported in animals. In this study, 9 aged pigs (6-12 years old) were histopathologically examined for gallbladder proliferative lesions. At necropsy, a large gallstone occupied the lumen of the gallbladder of 3 pigs. Histopathological examination revealed chronic cholecystitis in all 9 pigs, mucosal hyperplasia in 2 pigs, adenoma in 1 pig, and adenocarcinoma in 2 pigs. Bacilli were detected in the gallbladder lumen of 6 pigs by Warthin-Starry stain. Mucosal hyperplasia, adenoma, and adenocarcinoma were characterized by papillary projections of the mucosa with occasional acinar structures. Tumor invasion of the surrounding tissue was observed in the cases of adenocarcinoma. On Alcian blue and periodic acid-Schiff double-stained sections, the acinar structure of gallbladder mucosa in chronic cholecystitis and mucosal hyperplasia was stained in a mosaic pattern, indicating pyloric gland metaplasia. The results of immunohistochemistry revealed a CD10-positive epithelial brush border and mucin (MUC) 2-positive goblet cells in chronic cholecystitis, adenoma, and adenocarcinomas, indicating intestinal metaplasia. Immunoreactivity of MUC5 AC and cytokeratin 19 was weaker in adenoma and adenocarcinomas compared with the normal and hyperplastic gallbladder mucosa. The number of p53-positive nuclei and the Ki-67 index were higher in adenocarcinomas compared with benign lesions. These results suggest that chronic cholecystitis associated with gallstones and/or bacterial infections may contribute to metaplastic changes and development of gallbladder tumors in aged pigs. Alteration of mucin, cytokeratin, and p53 profiles in gallbladder proliferative lesions in pigs were similar to that in humans, suggesting a common pathogenesis in tumor development.

Distribution and Restoration of Serotonin-Immunoreactive Paraneuronal Cells During Caudal Fin Regeneration in Zebrafish.

Aquatic vertebrates possess diverse types of sensory cells in their skin to detect stimuli in the water. In the adult zebrafish, a common model organism, the presence of such cells in fins has only rarely been studied. Here, we identified scattered serotonin (5-HT)-positive cells in the epidermis of the caudal fin. These cells were distinct from keratinocytes as revealed by their low immunoreactivity for cytokeratin and desmosome markers. Instead, they were detected by Calretinin (Calbindin-2) and Synaptic vesicle glycoprotein 2 (SV2) antibodies, indicating a calcium-regulated neurosecretory activity. Consistently, electron microscopy revealed abundant secretory organelles in desmosome-negative cells in the fin epidermis. Based on the markers, 5-HT, Calretinin and SV2, we referred to these cells as HCS-cells. We found that HCS-cells were spread throughout the entire caudal fin at an average density of 140 cells per mm2 on each fin surface. These cells were strongly enriched at ray bifurcations in wild type fins, as well as in elongated fins of another longfin mutant fish. To determine whether hydrodynamics play a role in the distribution of HCS-cells, we used an interdisciplinary approach and performed kinematic analysis. Measurements of particle velocity with a fin model revealed differences in fluid velocities between bifurcated rods and adjacent non-bifurcated regions. Therefore the accumulation of HCS-cells near bone bifurcations may be a biological adaptation for sensing of water parameters. The significance of this HCS-cell pattern is reinforced by the fact, that it is reestablished in the regenerated fin after amputation. Regeneration of HCS-cells was not impaired by the chemical inhibition of serotonin synthesis, suggesting that this neurotransmitter is not essential for the restorative process. In conclusion, our study identified a specific population of solitary paraneurons in the zebrafish fin, whose distribution correlates with fluid dynamics.

Cytokeratin expression profiles of canine epithelial tissues.

Cytokeratins (CKs) are intermediate filaments of epithelial cells. In humans, different types of epithelia as well as their neoplasms show distinct CK expression profiles. The aim of this study was to establish a panel of CKs for the identification of specialized canine epithelia that can be integrated in a routine diagnostic setting. Immunohistochemistry was performed on 42 formalin-fixed paraffin-embedded (FFPE) canine unaltered tissues including all epithelial tissues by using an antibody panel detecting CKs 7, 8, 13, 14, 17, 19 and 20 and the pancytokeratin marker AE1/AE3. Using this antibody panel, a differentiation scheme for the identification of canine tissues was developed. This allowed the identification of 23 out of the 42 examined canine tissues and the distinction of 9 groups of specialized epithelia. The statistical validation revealed high variations in the immunoreactivity for CKs 7, 8, 14, 17 and 20 between the donor dogs. The antibody detecting CK 7 (OV-TL 12/13) showed a decrease in immunostaining after a fixation time of 3 and 4 days. To the best of the authors' knowledge this is the first study that characterizes all canine epithelial tissues for their expression of CKs 7, 8, 13, 14, 17, 19 and 20 and the pancytokeratin marker AE1/AE3. Results of this study are an important prerequisite for comparative histology and for the investigation into similarities/differences of the cytokeratin expression between normal and neoplastic epithelia. Since this study was performed on FFPE tissue, it can be included in the workflow of a routine diagnostic laboratory.

Effects of secretome on cisplatin-induced testicular dysfunction in rats.

Background:Testicular dysfunction is a degenerative disorder characterized by failure in the synthesis of reproductive hormones and spermatogenesis. Secretome derived from the human umbilical mesenchymal stem cell (MSC) has been reported to repair some degenerative disorders.Aim:This study aimed to investigate the effect of secretome derived from the human umbilical MSCs on cisplatin-induced testicular dysfunction in rats.Materials and Methods:Thirty-six male Wistar rats were divided into the control and secretome-treated groups. In the secretome-treated group, testicular dysfunction was induced by 3 mg/kg BW of cisplatin intraperitoneally 3 times with 3-day intervals. The secretome-treated group was divided according to dose: Low-dose (0.2 mL/kg BW) and high-dose (0.5 mL/kg BW) groups. Secretomes were injected intraperitoneally once a week for 3 weeks. 1 week after the injection of secretome, the cauda epididymis of the rats was removed for spermatozoa evaluation and histological examination.Result:After the injection of secretome, the sperm motility of the high-dose group showed thin wave-like, rare, and slow movements. No abnormal sperm morphology was observed in all the treated groups. The number of spermatozoa increased gradually in the high-dose group after the injection of secretome. The developmental stages of the spermatogenic cells were complete in both spermatozoa groups after the injection of secretome. However, the spermatozoa in the seminiferous tubules of the high-dose group were denser. Vimentin and cytokeratin immunoreactivities were very strong in the high-dose group 1 week after the second secretome injection.Conclusion:High-dose secretome derived from the human fetal umbilical cord could increase the number and motility of sperms in rats with cisplatin-induced testicular dysfunction. The administration of high-dose secretome was effective 1 week after the second dose, as indicated by very strong immunoreactivity for vimentin and cytokeratin. Moreover, secretome could promote the regeneration of the seminiferous tubules of both the groups.

Metastatic Renal Cell Carcinoma as Solitary Subcentimeter Polypoid Gastric Mucosal Lesions: Clinicopathologic Analysis of Five Cases.

BackgroundThe stomach is an uncommon site for metastatic carcinoma. Approximately 6% of renal cell carcinomas (RCCs) may metastasize to the stomach. The majority of the reported metastatic RCCs in the stomach presented as large masses or ulcers greater than a centimeter in size. It is very rare to encounter metastatic RCC as a solitary small polypoid gastric mucosal lesion.MethodsIn this study, we collected surgical pathology cases of gastric metastasis from RCC that measured 1.0 cm or less at the time of endoscopy. The clinicopathological characteristics were analyzed.ResultsFive patients with subcentimeter metastatic RCC involving the gastric mucosa were identified. The clinical presentation for upper endoscopic examination was non-specific. Two of the five patients did not have a known history of RCC. In the three patients with a previous history of RCC, the interval from primary RCC diagnosis to the detection of gastric mucosal metastasis was 5, 6, and 10 years, respectively. Endoscopically, all the lesions were solitary, ranging in size from 0.4 to 1 cm. Histologically, all five cases were of the clear cell type consisting of a bland clear cell proliferation within the lamina propria. Although the tumor cells were relatively bland, the presence of clear cytoplasm, nuclear membrane irregularity, occasional enlarged hyperchromatic atypical nuclei, and destructive growth in the center of the lesion should promote immunohistochemical workup. Immunohistochemically, the RCC cells exhibited at least patchy immunoreactivity for cytokeratin and RCC markers. In two cases, there were many CD68 positive foamy histiocytes intermingled with the tumor cells.ConclusionMetastatic RCC can rarely present as subcentimeter polypoid gastric mucosal lesions. The remote or unknown history of RCC, the non-specific endoscopic appearance, and the bland histological features may lead to a potential diagnostic pitfall. It is of importance to raise the awareness of such an unusual presentation of metastatic RCC in the stomach and to include metastatic RCC in the differential diagnosis for gastric mucosal polyps with clear cell morphology.

Immunohistochemical characterization of brush cells in the rat larynx.

The immunohistochemical characteristics of brush cells in the laryngeal mucosa were examined using immunohistochemistry for various immunohistochemical cell markers including villin at the light and electron microscopic levels. Cells that were immunoreactive to villin were barrel-shaped with thick cytoplasmic processes extending toward the lumen of the laryngeal cavity. Immunoelectron microscopic observations revealed thick and short microvilli with long rootlets of microfilaments. Numerous small clear vesicles and small finger-like cytoplasmic processes were observed in the apical process and lateral membrane, respectively. Double immunofluorescence showed villin-immunoreactive cells were not immunoreactive for the markers of solitary chemosensory cells, GNAT3 and phospholipase C, β2-subunit (PLCβ2), or for that of neuroendocrine cells, synaptosome-associated protein 25kD. Furthermore, immunoreactivities for cytokeratin 18 (CK18) and doublecortin like-kinase 1 in the perinuclear cytoplasm of villin-immunoreactive cells. However, some CK18-immunoreactive cells were immunoreactive to GNAT3 but not to villin. Regarding sensory innervation, only a few intraepithelial nerve endings with P2X3, SP, or CGRP immunoreactivity attached to villin-immunoreactive cells. In the present study, brush cells in the rat laryngeal mucosa were classified by immunoreactivity for villin, and were independent of other non-ciliated epithelial cells such as solitary chemosensory cells and neuroendocrine cells.

The differential diagnosis between pleural sarcomatoid mesothelioma and spindle cell/pleomorphic (sarcomatoid) carcinomas of the lung: evidence-based guidelines from the International Mesothelioma Panel and the MESOPATH National Reference Center

Immunohistochemistry is used to distinguish sarcomatoid malignant mesotheliomas (SMM) from spindle cell and pleomorphic carcinomas (SPC) but there are no guidelines on how to interpret cases that show overlapping or equivocal immunohistochemical findings. A systematic literature review of the immunophenotype of these lesions was performed and the experience with 587 SMM and 46 SPC at MESOPATH was collected. Data were analyzed with Comprehensive Meta-Analysis 2.0 software (Biostat, Englewood, NJ). There were insufficient data to evaluate the differential diagnosis between SPC and localized SMM or peritoneal SMM. Meta-analysis showed considerable overlap in the immunophenotype of these neoplasms and significant data heterogeneity amongst many of the results. Survival data from MESOPATH patients showed no significant differences in overall survival between SMM and SPC patients. Best available evidence was used to formulate several evidence-based guidelines for the differential diagnosis between pleural SMM and SPC. These guidelines emphasize the need to correlate the histopathological findings with clinical and imaging information. Diffuse SMM can be diagnosed with certainty in the presence of malignant spindle cell pleural lesions showing immunoreactivity for cytokeratin and mesothelial markers and negative staining for epithelial markers. Criteria for the interpretation of various other combinations of immunoreactivity for cytokeratin and mesothelial and/or epithelial markers are proposed. Localized sarcomatoid mesotheliomas can only be diagnosed in the presence of spindle cell malignancies that exhibit immunoreactivity for cytokeratin and mesothelial markers and negative immunoreactivity for epithelial lesions, in patients that show no multifocal or diffuse pleural spread and no evidence for extrapleural lesions.