S-100 Protein Immunoreactivity Research Articles

Immune Cell Profiling in the Ovarian Stroma of a Viviparous Fish during the Breeding Season: A Histological and Immunohistochemical Investigation

The molly fish is a member of viviparous teleosts that are characterized by the fusion of the right and left ovaries during their early embryonic development. This fusion results in a singular and saccular ovary, where the germinal epithelium lines the internal lumen. The present study aimed to identify the immune cells in the ovarian stroma of Molly fish during the breeding season using histological and immunohistochemical analysis. Histological examination of the ovaries displayed oocytes at all different stages of development and degeneration. The ovocoel, a lymph-filled space, remains in the center of the ovary and branches posteriorly, creating the lumen of the gonoduct. The ovarian wall is composed of three layers: the mesothelium, tunica albuginea, and germinal epithelium. The developing ova were held together by the stroma, which consisted of vascular collagenous connective tissue clustered with immune cells. Immunohistochemical analysis revealed the presence of clusters of macrophages expressing APG5, IL-1β, TGF-β, S100, NF-κB, CD68, Iba-1, and Ach. Monocytes demonstrated positive immunoreactivity for both APG5 and IL-1β, whereas dendritic cells expressed only APG5. Furthermore, rodlet cells exhibited immunoreactivity for S100 protein, IL-1β, NF-κB, CD68, Nrf2, Ach, myostatin, SOX9, and Iba-1. In contrast, stem cells displayed immunoreactivity for Nrf2, myostatin, and SOX9. In conclusion, the ovarian stroma of Molly fish demonstrated a notable presence of immune cells, indicating their active involvement in immune reactions.

Novel NONO::TFE3 fusion and ALK co-expression identified in a subset of cutaneous microcystic/reticular schwannoma.

Microcystic/reticular schwannoma (MRS) is a benign variant of schwannoma with a predilection for the gastrointestinal tract and skin. To date, genetic characterization of this tumor is limited. Prompted by the identification of TFE3::NONO fusion and ALK overexpression in an index case of MRS, a cohort of tumors was collected from institutional and consultation archives of two institutions. Next-generation sequencing (NGS), TFE3 fluorescence in situ hybridization (FISH), and TFE3 and ALK immunohistochemistry were performed, while clinicopathologic variables were documented. Eighteen MRS cases were identified (35 to 85 years) arising in the skin (n=8), gastrointestinal tract (n=5), adrenal gland (n=3), abdominal wall (n=1), and unknown site (n=1). Tumors showed a circumscribed to multinodular to plexiform low-power architecture with variable amounts of microcystic/reticular and solid schwannian components. Mitotic figures were scarce (0-1/10 HPFs), and atypia was absent. S100 protein and/or SOX10 immunoreactivity was noted in the microcystic/reticular and schwannian areas of all cases. NGS performed on two cutaneous tumors yielded NONO exon 12 fusion with TFE3 exon 4, and these lesions also showed HMB45 and ALK expression. Two additional cases showed ALK expression (1 weak), while a third was positive for TFE3, but these cases failed to show ALK or TFE3 rearrangement by FISH/NGS. There were no morphologic variables that correlated with the presence of NONO::TFE3. We identified a subset of microcystic/reticular schwannomas with NONO::TFE3 fusions and ALK co-expression, adding to the cohort of mesenchymal neoplasms that show ALK overexpression without rearrangement of the ALK gene.

Catfish Epidermal Club Cell Morphologic and Immunologic Attributes: Heterogeneous S-100 Immunoreactivity and Possible Neuroendocrine Function.

The fish epidermis (EP) contains several cell types, and it has several functional roles, though the secretory role prevails. The alarm or epidermal club cells (ECCs) represent a voluminous immune cell secreting an alarm substance. Our work targeted the histochemical and immunologic attributes of the ECCs in catfish. Matrix metalloproteinase (MMP-9) immunostaining revealed strong immunoreactive signals in the cytoplasm of all ECCs, while S-100 protein immunoreactivity selectively marked the ECCs. Individual ECCs exhibit intense S-100 immunoreactivity compared to neighboring ECCs. The difference in the intensity of the S-100 immunostaining was associated with the difference in the ECC size. This was confirmed by the semithin results where several developmental stages of ECCs could be distinguished. Some eosinophilic granular cells with their characteristic metachromatic granules were recorded juxtaposing the ECCs. Moreover, some free electron-dense granules could be demonstrated in the intercellular spaces surrounding the ECCs. Collectively, these findings suggest several functional profiles for the catfish ECCs depending on their developmental stage. Most importantly, S-100 immunoreactivity in the ECCs suggests its neuroendocrine function. Moreover, the difference in the intensity and polar distribution of S-100 staining is a sign of its role in the differentiation of the ECCs.

Cutaneous Melanocytic Tumor with CRTC1::TRIM11 Fusion: Review of the Literature of a Potentially Novel Entity.

Simple SummaryMolecular profiling of unclassified neoplasms has been pivotal in the characterization of new entities. Cutaneous melanocytic tumor with CRTC1::TRIM11 fusion (CMTCT) is a newly described neoplasm that falls into the broad category of diagnostically challenging dermal proliferations with melanocytic differentiation. The aim of this review is to educate colleagues about the clinical, histopathologic, and molecular features of CMTCT, and provide important information on the differential diagnosis.“Cutaneous melanocytic tumor with CRTC1::TRIM11 fusion” (CMTCT) is a recently described entity belonging to the family of superficial tumors displaying melanocytic differentiation. Thirteen cases have been reported so far, on the head and neck, extremities, and trunk of adults of all ages (12 cases) and one in an 11-year-old child. Histopathologically, it is a nodular or multilobulated tumor composed of spindle and epithelioid cells arranged in nests, fascicles, or bundles that are surrounded by thin collagenous septa. By immunohistochemistry, the tumor shows variable immunoreactivity for S100-protein, SOX10, and MITF, as well as specific melanocytic markers such as MelanA and HMB-45. The neoplasm’s biologic behavior remains uncertain since the reported cases are limited and the follow-up is short (median 12 months). However, local recurrence and synchronous distant metastasis after 13 years of initial resection has been described in one case. Herein, we present a comprehensive literature review of CMTCT hoping to raise awareness among the dermatopathologists of this potentially novel entity.

Solitary polypoid ganglioneuroma in the sigmoid colon: a rare finding during colonoscopy

Ganglioneuromas (GN) are rare, benign tumours of the autonomic nervous system which are seldom encountered in the gastrointestinal tract. They may occur as solitary lesions or more commonly as multiple lesions, also known as ganglioneuromatosis. Endoscopically they have no identifiable phenotypic characteristics and therefore diagnosis can only be confirmed through histological analysis. Microscopically they are composed of ganglion cells, nerve fibres and Schwann cells and show S-100 protein immunoreactivity. Clinically, there are no specific symptoms eluding towards the diagnosis of solitary ganglioneuromas of the gastrointestinal tract with most patients remaining asymptomatic. Due to their rarity, no guidelines current exists for solitary colonic GNs, however consensus exists that endoscopic resection is curative with no evidence of recurrence following total excision. This case gives an account of a solitary colonic ganglioneuroma in the sigmoid colon encountered during a screening colonoscopy in a 47-year-old male.

Melatonin administration provokes the activity of dendritic reticular cells in the seminal vesicle of Soay ram during the non-breeding season

Dendritic cells (DCs) are innate immune cells which engulf, process and present antigens to the naïve T-lymphocyte cells. However, little is known about the effect of melatonin on the DCs. The present study aimed to investigate the morphology and distribution of the DCs by transmission electron microscopy and Immunohistochemistry after melatonin administration. A total of 8 out of 15 adult ram was randomly selected to receive the melatonin implant and the remaining 7 animals received melatonin free implants. DCs showed positive immunoreactivity for CD117, S-100 protein and CD34. There is an obvious increase in the number of the positive immunoreactive cells to CD3, estrogen receptor alpha and progesterone in the treated groups. The expression of CD56 and MHCII in the DCs was abundant in the treated groups. The ultrastructure study revealed that melatonin exerts a stimulatory effect on the DCs which was associated with increment in the secretory activity of DCs. The secretory activity demarcated by an obvious increase in the number of mitochondria, cisternae of rER and a well-developed Golgi apparatus. The endosomal- lysosomal system was more developed in the treated groups. A rod-shaped Birbeck granule was demonstrated in the cytoplasm of the melatonin treated group. DCs were observed in a close contact to telocytes, T-Lymphocytes, nerve fibers and blood vessels. Taken together, melatonin administration elicits a stimulatory action on the DCs and macrophages through increasing the size, the number and the endosomal compartments which may correlate to increased immunity.

Congenital cutaneous neurofibromas in neurofibromatosis type1: Clinicopathological features in early infancy.

Clinicopathological features of cutaneous neurofibromas presenting as large irregularly shaped congenital café-au-lait macules (CALM) in Neurofibromatosis type1 (NF1) patients have not been well characterized. We aimed to analyze the histopathological findings of large "atypical" CALM in children with NF1. In this retrospective observational study we analyzed histopathological and immunostaining features of 21 biopsy specimens from 18 large hyperpigmented macules with irregular borders with or without hypertrichosis present during the first months of life in NF1 diagnosed children. Of the 21 biopsies, ten showed a diffuse neurofibroma pattern and four exhibited characteristics of plexiform neurofibroma (PNF). In twelve specimens we observed groups of fusiform cells arranged linearly mimicking a small caliber nerve trunk with abnormal morphology. Repeated biopsies from two of these lesions performed at different ages showed transformation to a plexiform pattern. An increased interstitial cellularity was observed in 17 samples that was more evident around eccrine glands in 16 or accompanying hair follicles and vascular structures in twelve samples. All these cells had immunoreactivity for S100-protein, CD68 and were Melan-A positive in 15 samples. Clinicopathological findings of congenital cutaneous neurofibromas provide early diagnostic clues of NF1 with high relevance for monitoring of these patients.

Sebaceous carcinoma in an 8-year old female Boerboel

Summary An uncommon case of metastatic sebaceous carcinoma from an 8-year-old female Boerboel dog was presented to the Truthmiles Veterinary Hospital Lagos, Nigeria. The protruding neoplastic mass was about 6 × 5 × 4 cm with a crater of about 2 cm deep oozing out purulent exudate on the left prescapular region of the left forelimb. After cytological and haematological evaluations, the tumour was processed histopathologically and immunohistochemically. Cytologically, the neoplastic cells appeared individually and in clusters. Cluster cells were round to oval. The nuclei were hyperchromatic, pleomorphic and exhibiting marked anisonucleoliosis. The cytoplasm was moderately basophilic and contained numerous varying sized fine vacuoles. Haematology revealed normocytic normochromic anaemia. Histopathology showed tumour cells characterized by variable degree of sebaceous differentiation, cellular and nuclear pleomorphism, metastases with considerable numbers of mitotic figures. Immunohistochemical evaluation showed strong positive cytoplasmic pan-cytokeratin expression and negative immunoreactivity for S-100 protein. In conclusion, the gross, cytological, histopathological and immunohistochemical features were suggestive of sebaceous carcinoma. To the author's knowledge, this appear to be the first reported case of sebaceous carcinoma in Boerboel breed.

Clear Cell Sugar Tumour

A 56-year-old female smoker with a history of right breast cancer (T1N0M0) had an incidental finding of an 8-mm right lower lobe solitary pulmonary nodule on computed tomography scan. The lesion was not positron emission tomography avid; however, it slowly progressed in size on surveillance computed tomography to 11 mm. She proceeded to thoracotomy and right lower lobectomy with lymph node sampling. Histology confirmed a clear cell sugar tumour. Clear cell sugar tumour of the lung is a remarkably rare benign pulmonary neoplasm of perivascular epithelioid origin, and a member of the PEComatous group of tumours. PEComas of the lung are divided into lymphangioleiomyomatosis, benign PEComas (including clear cell sugar tumour), and malignant PEComas. PEComas can be found in other sites, including the female genital and gastrointestinal tracts. The tumours characteristically contain a large amount of glycogen; therefore, leading differentials to consider are metastatic renal cell carcinoma and clear cell pulmonary carcinomas. Diagnosis is established by demonstrating immunoreactivity for human melanoma black (HMB-45) and S-100 protein, with no reactivity for cytokeratin 7 or epithelial membrane antigen. The general recommendation is for surgical resection without adjuvant chemotherapy.

A Distinct Malignant Epithelioid Neoplasm With GLI1 Gene Rearrangements, Frequent S100 Protein Expression, and Metastatic Potential: Expanding the Spectrum of Pathologic Entities With ACTB/MALAT1/PTCH1-GLI1 Fusions.

ACTB-GLI1 fusions have been reported as the pathognomonic genetic abnormality defining an unusual subset of actin-positive, perivascular myoid tumors, known as "pericytoma with the t(7;12) translocation." In addition, GLI1 oncogenic activation through a related MALAT1-GLI1 gene fusion has been recently reported in 2 unrelated gastric tumors, namely plexiform fibromyxoma and gastroblastoma. Triggered by unexpected targeted RNA-sequencing results detecting GLI1-related fusions in a group of malignant neoplasms with round to epithelioid morphology, and frequently strong S100 protein immunoreactivity, we investigated their clinicopathologic features in relation to other known pathologic entities sharing similar genetics. On the basis of a combined approach of targeted RNA sequencing and fluorescence in situ hybridization screening, we identified 6 cases with GLI1 gene fusions, including 4 fused to ACTB, 1 with MALAT1 and 1 with PTCH1 gene. Patients had a mean age of 36 years at diagnosis (range, 16 to 79 y) and slight female predilection all except 1 tumor originated in the soft tissue. Microscopically, the tumors had a monomorphic epithelioid phenotype arranged in a distinctive nested or cord-like architecture, separated by thin septae and delicate capillary network. All except 2 cases were strongly positive for S100 protein, whereas being negative for SOX10, SMA, and EMA. Only 1 tumor showed focal cytokeratin positivity in rare cells. Although the tumors showed some resemblance to pericytic/glomus tumors or myoepithelial tumors, the immunoprofile was not supportive of either lineage. Moreover, in contrast to the benign course of so-called pericytoma with t(7;12), 3 patients in this series developed metastatic disease to either lymph nodes or lung. In fact the only patient with lung metastases showed a novel PTCH1-GLI1 gene fusion. It remains to be determined whether these tumors represent a clinically and immunohistologically distinct subset of pericytoma, or an altogether novel soft tissue sarcoma. Our findings open new opportunities for targeted therapy, as tumors with GLI1 oncogenic activation, and subsequent PTCH1 overexpression, might be sensitive to sonic hedgehog pathway inhibitors.

Role of the Epipapillary Membrane in Maculopathy Associated with Cavitary Optic Disc Anomalies: Morphology, Surgical Outcomes, and Histopathology.

Purpose To evaluate the surgical outcomes of pars plana vitrectomy (PPV) with epipapillary membrane removal in patients with maculopathy associated with cavitary optic disc anomalies. Methods Eight patients (8 eyes) with cavitary optic disc anomaly-associated maculopathy who underwent PPV with epipapillary membrane removal were retrospectively reviewed. The best-corrected visual acuity (BCVA) and macular and papillary morphologies using enhanced depth imaging optical coherence tomography (EDI-OCT) were evaluated before and after treatment. Immunohistochemistry for an intraoperatively excised epipapillary membrane tissue was also performed. Results Before surgery, EDI-OCT revealed that epipapillary membrane was observed in all patients. Retinoschisis was resolved with no recurrence in all patients following vitrectomy regardless of a disease type or the presence or absence of preoperative posterior vitreous detachment. The mean final BCVA and central retinal thickness significantly improved compared with pretreatment values (P = 0.008 and 0.004, resp.). Immunoreactivity for S100 protein and glial fibrillary acidic protein, markers of astrocytes, was positive in the resected membrane tissues. Conclusions These results suggest that epipapillary membrane is involved in the pathogenesis of some patients with cavitary optic disc anomaly-associated maculopathy as well as posterior hyaloid membrane. PPV with epipapillary membrane removal may be a useful treatment option for this maculopathy. This trial is registered with UMIN000011123.

Astroblastoma: a distinct tumor entity characterized by alterations of the X chromosome and MN1 rearrangement.

Astroblastoma is a rare, enigmatic tumor of the central nervous system (CNS) which shares some clinicopathologic aspects with other CNS tumors, especially ependymoma. To further clarify the nature of astroblastoma, we performed clinicopathologic and molecular genetic studies on eight cases of astroblastoma. The median age of the patients was 14.5 years, ranging from 5 to 60 years, and seven of the patients were female. All tumors arose in the cerebral hemisphere and radiologically appeared to be well-bordered, nodular tumors often associated with cystic areas and contrast-enhancement. Six of the seven patients with prognosis data survived without recurrences during the follow-up periods ranging from six to 76 months. One patient had multiple recurrences and died six years later. All tumors exhibited salient microscopic features, such as being well demarcated from the surrounding brain tissue, perivascular arrangement of epithelioid tumor cells (represented by "astroblastic" pseudorosettes, trabecular alignment, and pseudopapillary patterns), and hyalinized blood vessels. Immunoreactivity for GFAP, S-100 protein, Olig2, and EMA was variably demonstrated in all tumors, and IDH1 R132H and L1CAM were negative. Array comparative genomic hybridization revealed numerous heterozygous deletions on chromosome X in the four tumors studied, and break-apart fluorescence in situ hybridization demonstrated rearrangement of MN1 in five tumors with successful testing. The characteristic clinicopathologic and genetic findings support the idea that astroblastoma is distinct from other CNS tumors, in particular, ependymoma. In addition, MN1 rearrangement and aberrations of chromosome X may partly be involved in the pathogenesis of astroblastoma.

Plasmacytoid Myoepithelioma of the Hard Palate: Case Report.

BackgroundMyoepitheliomas are uncommon salivary gland neoplasms consisting entirely or predominantly of cells with myoepithelial phenotype. They commonly involve the parotid gland and the minor salivary glands of the palate.AimA case of plasmacytoid myoepithelioma of the hard palate is described.Case description and resultsA 55-year-old woman presented to her oral surgeon with a tumor on the hard palate. Microscopic examination showed a well-circumscribed but non-encapsulated tumor, consisting mostly of plasmacytoid cells in a loose fibrovascular stroma. Neoplastic myoepithelial cells showed immunoreactivity for S-100 protein, CK AE1/AE3 (Figure 5b), GFAP, calponin, and CD138/Syndecan-1. Total excision of the tumor under local anesthesia was performed and no recurrence was noted 14 months after treatment.ConclusionsSince plasmacytoid myoepithelioma is uncommon, minor salivary glands, its immunohistochemical features, management and prognosis should be further investigated.

Immunohistochemical study of sustentacular cells in adrenal medulla of neonatal and adult rats using an antibody against S-100 protein

This study was performed to investigate the light microscopic features of sustentacular cells in adrenal medulla in neonatal and adult male albino rats using an antibody against S-100 protein. S-100 expression in sustentacular cells is considered a reliable cell marker for this type of cells. Twenty-four male albino rats were allocated into two groups, neonatal group (1 week old, 12 rats) and adult group (3 months old, 12 rats). Paraffin sections of the adrenal glands were immunostained for the expression of S-100 protein. The results demonstrated differences in distribution, arrangement and structure of sustentacular cells in adrenal medulla in neonatal and adult rats. All sustentacular cells of adrenal medulla in all animals showed intense immunoreactivity for S-100 protein in their nuclei, perikarya, and cytoplasmic processes. Most of S-100 immunopositive sustentacular cells in adrenal medulla of neonatal rats are few, dispersed, small in size, and oval in shape with thin short bipolar cytoplasmic processes. These cells in adult rats are more numerous, larger in size, and stellate in shape with numerous slender, longer branched cytoplasmic processes. This study indicated that adrenal medullary sustentacular cells showed obvious morphological postnatal changes with aging suggesting structural and functional maturation.

Atypical Granular Cell Tumor of the Larynx: Report of an Unusually Aggressive Tumor

Introduction: Granular cell tumors are uncommon benign neoplasms. The head and neck is the most common site, usually localized to the anterior tongue. The larynx is rarely involved, representing 1.6% to 3.7%. Case report: We present the case of a 31-year-old, non-smoking female, with a history of recurrent cysts in the pyriform sinus. She consulted for dyspnea. By physical exam, there were no specific findings in head and neck area. Cervical computed tomography demonstrated a tissular mass in the laryngeal area. Laryngoscopy showed a submucosal tumor of the aryepiglottic fold. A biopsy was performed. Histopathological examination revealed round or oval-shaped tumor cells with abundant eosinophilic granular cytoplasm. The nuclei are sometimes small and regular and sometimes hyperchromatic and pleomorphic. The tumor cells showed immunoreactivity for S100 protein and vimentin. The tumor was diagnosed as an atypical granular cell tumor. Conclusion: Pathologists should be aware of this exceptional lesion. So, that the patient could have appropriate treatment.

Recurrent NTRK1 Gene Fusions Define a Novel Subset of Locally Aggressive Lipofibromatosis-like Neural Tumors

The family of pediatric fibroblastic and myofibroblastic proliferations encompasses a wide spectrum of pathologic entities with overlapping morphologies and ill-defined genetic abnormalities. Among the superficial lesions, lipofibromatosis (LPF), composed of an admixture of adipose tissue and fibroblastic elements, in the past has been variously classified as infantile fibromatosis or fibrous hamartoma of infancy. In this regard, we have encountered a group of superficial soft tissue tumors occurring in children and young adults, with a notably infiltrative growth pattern reminiscent of LPF, variable cytologic atypia, and a distinct immunoprofile of S100 protein and CD34 reactivity, suggestive of neural differentiation. SOX10 and melanocytic markers were negative in all cases tested. In contrast, a control group of classic LPF displayed bland, monomorphic histology and lacked S100 protein immunoreactivity. To define the pathogenetic abnormalities in these seemingly distinctive groups, we performed RNA sequencing for fusion gene discovery in 2 cases each, followed by screening for any novel alterations identified in a larger cohort representing both entities. The 2 index LPF-like neural tumors (LPF-NT) showed TPR-NTRK1 and TPM3-NTRK1 gene fusions, which were further validated by fluorescence in situ hybridization (FISH) and reverse transcription polymerase chain reaction. Subsequent FISH screening of 14 LPF-NT identified recurrent NTRK1 gene rearrangements in 10 (71%) cases. Of the NTRK1-negative LPF-NT cases, 1 case each showed ROS1 and ALK gene rearrangements. In contrast, none of the 25 classic LPFs showed NTRK1 gene rearrangements, although regional abnormalities were noted in the 1q21-22 region by FISH in a majority of cases. Furthermore, NTRK1 immunostaining was positive only in NTRK1-rearranged S100-positive LPF-NT but negative in classic LPF. These results suggest that NTRK1 oncogenic activation through gene fusion defines a novel and distinct subset of soft tissue tumors resembling LPF, but displaying cytologic atypia and a neural immunophenotype, provisionally named LPF-like neural tumors.

Enteroendocrine profile of α-transducin immunoreactive cells in the gastrointestinal tract of the European sea bass (Dicentrarchus labrax)

The fish sensory epithelium contains three types of sensory cells denominated ciliated, microvillous, and crypt neurons. Each one differs from the other in its morphological, ultrastructural and molecular features, as well as in their projections to the central nervous system. Crypt neurons are present in both bony and cartilaginous fish and can be identified on the basis of their morphology and the expression of some specific proteins and genes. In this study we have investigated the morphology of crypt neurons, as well as the occurrence and co-localization of S100 protein, calretinin and TRPV4, three proposed markers for crypt cells, in the olfactory epithelium of adult zebrafish (Danio rerio) using double immunofluorescence associated to laser confocal microscopy. A sparse population of superficial S100 protein positive cells was detected being identified as crypt neurons. The calretinin immunoreactive cells were more abundant, occasionally resembling the morphology of the crypt cells but never displaying co-localization of both proteins. The TRPV4 positive cells differed in morphology from crypt cells, thus excluding the occurrence of TRPV4 in those cells. These results demonstrate that only S100 protein immunoreactivity can be used to identify crypt cells. Because some calretinin positive cells showed localization and morphology similar to the crypt cells of the sensory epithelium, the occurrence of two subtypes of crypt cells, S100 protein and calretinin positive, cannot be excluded. The significance of these findings remains to be elucidated.

Immunohistochemical characterization of the crypt neurons in the olfactory epithelium of adult zebrafish

The fish sensory epithelium contains three types of sensory cells denominated ciliated, microvillous, and crypt neurons. Each one differs from the other in its morphological, ultrastructural and molecular features, as well as in their projections to the central nervous system. Crypt neurons are present in both bony and cartilaginous fish and can be identified on the basis of their morphology and the expression of some specific proteins and genes. In this study we have investigated the morphology of crypt neurons, as well as the occurrence and co-localization of S100 protein, calretinin and TRPV4, three proposed markers for crypt cells, in the olfactory epithelium of adult zebrafish (Danio rerio) using double immunofluorescence associated to laser confocal microscopy. A sparse population of superficial S100 protein positive cells was detected being identified as crypt neurons. The calretinin immunoreactive cells were more abundant, occasionally resembling the morphology of the crypt cells but never displaying co-localization of both proteins. The TRPV4 positive cells differed in morphology from crypt cells, thus excluding the occurrence of TRPV4 in those cells. These results demonstrate that only S100 protein immunoreactivity can be used to identify crypt cells. Because some calretinin positive cells showed localization and morphology similar to the crypt cells of the sensory epithelium, the occurrence of two subtypes of crypt cells, S100 protein and calretinin positive, cannot be excluded. The significance of these findings remains to be elucidated.

Original article Angiocentric glioma: a rare intractable epilepsy-related tumour in children

Angiocentric glioma is a low-grade tumour that occurs in children and young adults with a long-standing epilepsy. The typical histopathological features of this tumour is the presence of spindle-shaped cells, radially oriented around the cortical blood vessels. We present two teenage cases of the angiocentric variant of glioma: 1) a 15-year-old girl with a chronic and intractable partial epilepsy with cystic tumour located in the right temporal lobe and 2) a 14-year-old boy with intractable seizures and an extensive cortical lesion in the left parieto-occipital area. In both cases, the total tumours excision was performed. The histopathological findings revealed a characteristic angiocentric pattern that was composed of elongated cells arranging in pseudorosette-like structures around blood vessels. Moreover, schwannoma-like areas and subpial neoplastic infiltration with palisading of tumour cells at the brain surface were seen. The neoplastic cells displayed immunoreactivity for GFAP, S-100 protein and vimentin. A slight "dot-like" EMA staining, suggesting ependymal differentiation, was detected. The clinical and pathological picture allowed to establish the diagnosis of angiocentric gliomas. The patients were discharged home in a good condition and without seizures. During the 4-year follow-up, the tumour recurrence and seizures were not observed. The appropriate diagnosis of this peculiar type of usually low-grade glial tumour is important for adequate and successful treatment. The differential diagnosis requires the exclusion of other tumours with an angiocentric pattern, i.e. ependymoma, astroblastoma, which are associated with more aggressive biology.

A Case of a Granular Cell Tumor Arising from the Dorsal Side of the Tongue

We herein report a case of a granular cell tumor arising from the dorsal side of the tongue in a 45-year-old female. The patient had noticed a mass on the left dorsal side of the tongue seven months earlier, but had ignored it as it was painless. The lesion exhibited a hard, elastic, clear boundary measuring approximately 15 × 15 mm on the left side of the back of the tongue. A biopsy was performed, and the lesion was diagnosed as a granular cell tumor. The tumor was resected, including the surrounding normal tissue. Histopathologically, it consisted of uniform cells with many eosinophilic granules in the cytoplasm and pseudoepitheliomatous hyperplasia. On immunohistochemistry, the cytoplasm and nucleus displayed immunoreactivity for S-100 protein and CD68. No evidence of any local recurrence was observed during the one-year follow-up period.