Positive Cytoplasmic Reaction Research Articles

A Comparative Histological Study Between the Protective and the Therapeutic Effect of Probiotic on Cisplatin Induced Nephrotoxicity in Adult Male Albino Rat

Abstract Introduction Although cisplatin (CP) is one of the most effective chemotherapies, it is associated with significant nephrotoxicity (Acute kidney injury). Lactobacillus plantarum is often used as a probiotic on its own for its beneficial properties and anti-inflammatory activity. Aim to compare the protective and therapeutic role of probiotics on the microscopic structure of the kidney in a model of cisplatin-induced nephrotoxicity. Material and Methods thirty-five adult male albino rats weighing (200-220gm) were divided into 4 groups. Group I (control group), Group II (Cisplatin group): rats received intraperitoneal injection of CP (7.5 mg/kg) for 3 days. Group III (protective group): Rats received 1 mL of probiotic orally for 7 days. From the fifth day, the rats received intraperitoneal injections of CP (7.5mg/kg) for 3 days. Group IV (Therapeutic group): Rats received intraperitoneal injection of CP for 3 days. From the fourth day, the rats received probiotic L. plantarum orally at a dose of (1 mL/day) for 14 days. The concentration of probiotics in group III and group IV was 109 Colony forming units (CFU)/mL/100 g of body weight. Kidney specimens were proceeded for light microscopic examination, as well as Morphometrical and statistical analyses. Results H&E-stained sections of Group II showed marked renal affection in which most glomeruli showed atrophy. Renal tubules were mostly distorted, necrotic, and degenerative with interstitial hemorrhage, congestion, and cellular infiltration. PAS-stained sections showed marked increased reaction in glomerular and tubular Basement membranes with an apparent loss of Brush borders of most of the PCTs. Masson`s trichrome-stained sections showed a marked increase in collagen fibers in renal interstitia mostly around blood vessels. Immunohistochemically stained sections showed a marked increase in positive cytoplasmic reaction to caspase -3 antibodies mostly in renal tubules. On the other hand, the renal structure of The protective group showed marked improvement which appeared nearly comparable to that of the control group while the therapeutic group showed minimal improvement. Conclusion The protective effect of probiotics on cisplatin-induced Acute Kidney Injury (Nephrotoxicity) was markedly better than the therapeutic effect as detected by microscopic, morphometric, and statistical studies.

Granular cell tumor of the perineum (clinical case)

Aim: to present a clinical case of a rare granular cell tumor (Abrikosov’s tumor) with perianal site.Patients and Methods: a patient had a slowly progressive growth of a perianal tumor. The tumor with dimensions of 40 × 30 mm intimately adheres to the lower ampullary rectum and anterior portion of m. levator ani, no signs of malignant transformation occurred. Trepanobiopsy was performed followed by immunohistochemical study. The biopsies contain mainly fibrous tissue and clusters of cells with rounded nuclei and granular cytoplasm. Immunohistochemistry showed diffuse positive cytoplasmic reaction with antibodies to S100. The tumor was positive for CD8, vimentin and negative for GFAP. The expression of the Ki67 protein was 2%. Diagnosis: granulocellular tumor (Abrikosov’s tumor), the tumor was removed by perineal access.Resultss: the removal of the tumor, originating from the low rectum, was performed with perineal access and with the restoration of the muscular layer of the bowel wall. No complications occurred, patient discharged 5 days after surgery.Conclusion: Abrikosov’s tumor is a rare benign neoplasm. Surgery is possible in coloproctological units with sufficient level of surgeons.

Immunohistochemical Identification and Assessment of the Location of Immunoproteasome Subunits LMP2 and LMP7 in Acquired Cholesteatoma.

Cholesteatoma, accompanied by chronic inflammatory response, is characterized by invasive growth and osteolytic activity. As specific proteasome isoforms, the immunoproteasomes serve as an important modulator of inflammatory responses. The aim of the present study was to determine the biological activity of cholesteatoma through the analysis of the expression and localization of immunoproteasome subunits of low molecule weight protein (LMP) 2 and LMP7. Cholesteatoma specimens were obtained from 15 adults who underwent ear surgery due to acquired attic cholesteatoma. Normal skin specimens were taken from retro-auricular skin incisions from the same patients. The specimens were stained with anti-LMP7 antibody, using immunohistochemistry techniques based on the binding of biotinylated secondary antibody with the enzyme-labeled streptavidin and the Envision FLEX system. In all specimens of cholesteatoma, the immunohistochemical reaction with the antibody against the LMP2 was positive, in both the cytoplasm of the cholesteatoma matrix and the perimatrix. A negative reaction with anti-LMP2 was observed in the cytoplasm and nuclei of control skin cells. A positive nuclear and cytoplasmic immunohistochemical reaction with anti-LMP7 has been demonstrated in numerous cells, in both the matrix and perimatrix of cholesteatoma. We present evidence of the presence of expressions of LMP2 and LMP7 within cholesteatoma tissue. Our results might bring new information concerning immunoproteasome-dependent pathophysiologic mechanisms in cholesteatoma.

Idiopathic Granulomatous Mastitis with Incidental Lobular Carcinoma In Situ: A Case Report

Background: Lobular carcinoma in situ (LCIS) is a type of lobular neoplasia within the terminal duct lobular unit, involving more than half of acini. It is mostly diagnosed incidentally and although it is not a malignant lesion, it has an association with malignancy in the future. Idiopathic granulomatous mastitis (IGM) is a benign granulomatous disease with few simultaneous reports of malignant lesions in the literature. In this case report, we present a case with LCIS and IGM in a single breast.Case Presentation: A 35-year-old female presented to the breast clinic with complaints of pain and a palpable mass in the right breast. The past medical history, habitual history, drug history, and family history of cancer were negative. Physical examinations showed a palpable mass in the right breast without nipple discharge and retraction and lymphadenopathy and the left breast was intact. Breast imaging showed a right UOQ mass. A core needle biopsy was performed showing LCIS and IGM on the right side with a positive cytoplasmic reaction for P120 catenin. E-cadherin was negative in LCIS. P63 and CK5/6 immunostainings revealed the presence of myoepithelial cells around ductal and glandular structures. The patient developed erythema nodosum at the time of diagnosis. She was put on prednisolone 50 mg per day and NSAID, and after improvement was maintained on 25 mg daily prednisolone for about 7 months, combined with 3 months of hydroxychloroquine 200 mg twice a day. At the 12-month follow-up, both breasts were completely normal in the physical examination without any mass or skin changes and the right breast mass decreased in size.Conclusion: Radiologic findings of IGM can be suggestive of other possible causes and silent etiologies like the primary phase of breast cancer and LCIS should not be overlooked.

The features of BECN1 expression in the pyramidal layer of rat hippocampus in chronic cerebral ischemia

AbstractBackgroundBECN1 is a member of the Bcl‐2 protein superfamily, belonging to the BH3‐proteins subfamily, which performs many functions, including cross‐regulation of autophagy and apoptosis. BECN1 acts as regulator of the formation and maturation of autophagosomes, the development of neurodegenerative processes in the hippocampus and cerebellum in a BECN1‐knockout mice.MethodChronic cerebral ischemia modeled in rats by limiting cerebral blood flow with applying ligatures to the carotid arteries. The cognitive sphere, the preservation of reflexes, the ability to remember new objects, the degree of neuronal injury, and the level of BECN1 expression in the pyramidal layer of the hippocampus were evaluated. Immunohistochemical study was performed using polyclonal antibodies to BECN1, visualized using diaminobenzidine.ResultThe most pronounced changes were found in the pyramidal layer of the CA1, where neurons with signs of damage were identified along with unchanged neurons. Dystrophic changes in the pyramidal cells were of different severity, determined by a significant increase in the number of hyperchromic neurons, and in most of them total hyperchromia of the nucleus and cytoplasm was observed, a large number of shadow cells were formed. An immunohistochemical study of the hippocampus using antibodies to BECN1 revealed a uniform positive cytoplasmic reaction, mainly of low intensity. A significant increase in expression was found in the CA1, where the relative area of the immunoreactive material increased by 1.1% compared with the control (p <0.001) and reached 1.5%.ConclusionBECN1 is involved in the cross‐regulation of autophagy and apoptosis. According to modern concepts, BECN1 localized intracellularly in the complex with homologs‐proteins of the Bcl‐2 family. With dissociation of the Bcl‐2/BECN1 complex and an increase in free BECN1, autophagy is induced. The observed increase in the expression of BECN1 in CA1 indicates the inclusion of BECN1‐dependent autophagy in this zone in chronic cerebral ischemia.

Significance of nuclear factor - kappa beta activation on prostate needle biopsy samples in the evaluation of Gleason score 6 prostatic carcinoma indolence.

BackgroundThe goal of our study was to find out whether the immunohistochemical expression of nuclear factor-kappa beta (NF-κB) p65 in biopsy samples with Gleason score 3 + 3 = 6 (GS 6) can be a negative predictive factor for Prostate cancer (PCa) indolence.Patients and methodsStudy was conducted on a retrospective cohort of 123 PCa patients with initial total PSA ≤ 10 ng/ml, number of needle biopsy specimens ≥ 8, GS 6 on biopsy and T1/T2 estimated clinical stage who underwent laparoscopic radical prostatectomy and whose archived formalin-fixed and paraffin-embedded (FFPE) prostate needle biopsy specimens were used for additional immunohistochemistry staining for detection of NF-κB p65. Both cytoplasmic and nuclear NF-κB p65 expression in biopsy cores with PCa were correlated with postoperative pathological stage, positive surgical margins, GS and biochemical progression of disease.ResultsAfter follow-up of 66 months, biochemical progression (PSA ≥ 0.2 ng/ml) occurred in 6 (5.1%) patients, 3 (50%) with GS 6 and 3 (50%) with GS 7 after radical prostatectomy. Both cytoplasmic and nuclear NF-κB p65 expressions were not significantly associated with pathological stage, positive surgical margin and postoperative GS. Patients with positive cytoplasmic NF-kB reaction had significantly more frequent biochemical progression than those with negative cytoplasmic NF-kB reaction with PSA 0.2 ng/ml as cutoff point (p = 0.015) and a trend towards more biochemical progression with PSA ≥ 0.05 ng/ml as cutoff point (p = 0.068).ConclusionsCytoplasmic expression of NF-κB is associated with more biochemical progression and might be an independent prognostic factor for recurrence-free survival (RFS), but further studies including larger patient cohorts are needed to confirm these initial results.

Light and Electron Microscopic Studies on the Possible Protective Effect of Ginger on the Gastric Fundic Mucosa of Adult Male Albino Rats Treated with 5- Fluorouracil

Introduction: 5-fluorouracil is a potent antimetabolite chemotherapeutic medication used for treatment of various malignancies . Using this agent result in toxic effect mainly in the lining of digestive tract. To ameliorate 5 FU toxic effect ginger was implicated in this study.Aim of the Work: To evaluate the microscopic effect of 5-fluorouracil on gastric fundus mucosa in rat models . and to study the possible beneficial role of ginger in the ameliorations of these changes. Material and Methods: Forty-eight adult male albino rates were divided into four groups: group I (control), group II received ginger orally in a dose of 200 mg/kg/day , group III received 5-fluorouracil (15 mg/kg) intraperitoneally and group IV received 5 FU and Ginger as previous doses for 5 days. The fundic part of stomach was excised and subjected to light and electron microscopic studies.Results: In 5 FU treated group, the fundic gastric mucosa showed multiple areas of tissue loss , congested dilated blood vessels and extravasated red blood cells and mononuclear infiltration were seen between fundic gland cells. Parietal cells showed ballooned appearance, vacuolated cytoplasm, and pykontic nuclei. PAS/ Alcian blue stained sections showed marked reduction in both alcian blue and PAS positive reaction. There was strong positive cytoplasmic reaction in the apical and middle parts of the fundic glands for caspase 3 while large number of parietal cells were stained positive for Cox 2. These histological findings were improved after ginger administration. Histomorphometric study revealed significant weight reduction, increased mucosal ulcer depth, decreased mucosal thickness and increased number of parietal cells in 5 FU treated group when compared to control group. Conclusion: 5FU causes gastric damage in rat model. Ginger supplementation could be used to alleviate the damaging pathological effect on gastric fundus.

Efficacy of transforming growth factor- β on development of ameloblasts and odontoblasts in tooth germ of young albino rat

Transforming growth factors were known as secreted factors that induced the growth of non-transformed cells. The study investigating the growth response of ameloblasts and odontoblasts to TGF-β. Four adult male and 12 adult female albino rats were used in this study. Mating took place between them. Female rats were divided into two groups each group consist of 6 rats: group I (control) rats were injected with 0.1 m1 phosphate buffer saline every two days from the first day till the labor time. Their offspring were considered the control group. Group II were injected intramuscular with TGF-β 40 ng dissolved in PBS every two days during the pregnancy period. Thirty off-springs rats of both groups were killed after 4 days of birth and the lower jaw of each was dissected. The sections were stained by hematoxyline and eosin and immuno for histological study. All the data will statistically be analyzed. Histological examination of tissue sections, showed differences in ameloblast and odontoblastic layers. Enamel matrix, dentin and predentin layers showed variable thickness when compared to the control group. While Immunohistochemical examination of both ameloblasts and odontoblasts of group II showed negative nuclear and positive cytoplasmic reaction of MMP-9 in all stained tissue sections. It was concluded that: within the utilized doses and experiment duration, TGF-β was associated with noticeable histological changes in ameloblasts and odontoblasts. TGF-β has a relatively mild stimulatory effect on the organic matrix secretory potential of odontoblasts was observed in dentin.

Histological changes of the albino rat cerebellar cortex under the effect of different doses of tramadol administration

Background Tramadol hydrochloride is a centrally acting synthetic analgesic used to treat moderate to severe pain with a wide range of applications. Aim This study was designed to investigate the effect of tramadol on the histology of the cerebellar cortex in adult albino rats. Materials and methods Thirty adult male albino rats weighing about 200 g were used and divided into control and experimental groups. The latter group was subdivided into two subgroups (IIa and IIb). Rats of subgroup IIa and IIb were injected intraperitoneally with 0.7 and 1.8 mg as a single daily dose of tramadol solution for 2 weeks, respectively. Rats were killed after 2 weeks and decapitated. The cerebellum was removed and subjected to histological, immunohistochemical, and morphometric studies. Results Histological study of subgroup IIa showed mild distortion of Purkinje cells with destroyed mitochondria and cisternae of rough endoplasmic reticulum. Meanwhile, subgroup IIb showed Purkinje cells arranged in multilayer cells with obvious damage such as a small nucleus with an indented membrane. The granular layer contained small cells, most of which had lost their nuclei, whereas others showed condensed chromatin with a thin rim of cytoplasm. Results of inducible nitric oxide synthase reaction showed a moderately positive cytoplasmic reaction of granular and Purkinje cells in subgroup IIa. However, subgroup IIb showed a highly positive cytoplasmic reaction. Morphological study of the cerebellar layer thickness showed a significant decrease in the thickness of Purkinje and granular layers, with a significant increase in the thickness of the molecular layer in both experimental subgroups. The Purkinje cell count showed a significant decrease in its number in both experimental subgroups. Conclusion The results of this study provided evidence that tramadol intake exerts a neurotoxic effect on the cerebellar structure in an ascending manner according to the dose administered. Thus, the Ministry of Health should make efforts to control usage of this drug among teenagers and correct misconceptions about this medication.

Evaluating the Protective Role of Ginseng against Histological and Biochemical Changes Induced by Aflatoxin B1 in the Renal Convoluted Tubules of Adult Male Albino Rats

Background: Aflatoxins are secondary metabolites of the fungi Aspergillus flavus and Aspergillus parasiticus. Chronic aflatoxin exposure is associated with damage to many body organs including the kidneys. Aim of the work: The aim of this study was to investigate the effect of aflatoxin B1 on the renal convoluted tubules of adult male albino rats and to determine the possible protective role of ginseng. Materials and methods: Thirty six adult male albino rats were divided into three groups; group I: control group, group II (Aflatoxin B1 treated group): Aflatoxin B1 was administered 250 microgram/kg body weight/day, 5 days/ week for 4 weeks by oral gavages. Group III (Aflatoxin B1-Ginseng treated group): received the same dose of Aflatoxin B1 simultaneously with ginseng at a rate of 100 mg/kg body weight, by oral gavage. Blood urea nitrogen, serum creatinine and uric acid were measured. Renal cortex samples from, were processed for light and electron microscope examination. Results: Examination of Aflatoxin B1 treated group revealed deterioration of renal functions; various degrees of renal tubular affection in the form of vacuolated tubular cells and hyaline casts in the lumen of most tubules. Some tubular cells had small darkly stained nuclei while others had sloughed epithelial cells in their lumina. Weak positive cytoplasmic reaction of Bcl2 was detected in most renal tubular cells. These changes were markedly reduced with administration of ginseng in group III. Conclusion: Aflatoxin leads to alterations in the histological structure and functions of renal convoluted tubules of albino rats and ginseng supplementation could be protective from these changes.

Primary non-gestational pure choriocarcinoma arising in the ovary: A case report and literature review.

Pure non-gestational choriocarcinoma is a primary germ cell neoplasm that has been defined as a tumor without other germ cell elements. The current study presents an extremely rare case of non-gestational pure choriocarcinoma in a postmenarcheal young female and describes details of the tumor, including the clinicopathological findings. The patient was a 10-year-old female who underwent salpingo-oophorectomy. Histologically, the extensive hemorrhagic tumor was composed of choriocarcinoma without additional germ cell tumor components. The tumor cells were immunohistochemically positive for epithelial markers, including cytokeratins and epithelial membrane antigens, and there was a positive cytoplasmic reaction for β-human chorionic gonadotropin in the syncytiotrophoblasts. Furthermore, numerous tumor cells were immunohistochemically positive for the β2-microglobulin antibody. The patient received adjuvant cisplatin, etoposide and bleomycin chemotherapy, and is currently disease-free without evidence of recurrence or metastasis subsequent to 62 months of follow-up.

Effect of aromatase inhibitors on the endometrium and ovary with their possible role in ovulation in adult albino rats

Introduction Aromatase inhibitors act by inhibiting estrogen synthesis and depletion of its concentrations in the circulation. Aim The aim of the study was to investigate the effect of exemestane and letrozole on the endometrium and ovary with their possible role in ovulation in adult albino rats. Materials and methods Thirty adult female albino rats were used and divided into control and experimental groups. Rats in the experimental group were further divided into subgroup IIA and subgroup IIB. In subgroup IIA each rat was given exemestane at 1 mg/kg/day and in subgroup IIB each rat was given letrozole at 5 mg/kg/day by means of a gastric tube for five consecutive ovarian cycles. Specimens from their ovaries and endometrium were taken and prepared for H&E staining and for immunohistochemical staining for vascular endothelial growth factor study. Morphometric study of endometrial thickness and surface area percentage of immunoreaction in the endometrium was evaluated. Hormonal assay of luteinizing hormone and follicular stimulating hormone was carried out. Results Significant decrease in endometrial thickness was observed in the exemestane-treated group. The letrozole-treated group revealed significantly thickened endometrium. The exemestane-treated group showed markedly disturbed ovarian architecture in the form of thickened germinal epithelial cell layer and multiple corpora lutea with atretic follicles. The letrozole-treated group revealed an ovarian cortex with multiple stages of follicular development. The vascular endothelial growth factor immunoreaction of the letrozole-treated group showed significant highly positive cytoplasmic reaction. Significant decrease in luteinizing hormone level in the exemestane group and significant increase in the letrozole group were detected. Conclusion It is concluded that letrozole improved the endometrial thickness and may have a role in ovulation induction. In contrast, exemestane led to disruption of the endometrium and ovary. Therefore, not all aromatase inhibitors help in ovulation.

Post‐transcriptional regulation of fukutin in an astrocytoma cell line

Fukutin is the gene responsible for Fukuyama-type congenital muscular dystrophy (FCMD), an autosomal recessive disease associated with central nervous system (CNS) and eye anomalies. Fukutin is involved in basement membrane formation via the glycosylation of α-dystroglycan (α-DG), and hypoglycosylation of α-DG provokes the muscular, CNS and eye lesions of FCMD. Astrocytes play an important role in the pathogenesis of the CNS lesions, but the post-transcriptional regulation of fukutin mRNA has not been elucidated. In this study, we investigated the characteristics of fukutin mRNA using an astrocytoma cell line that expresses fukutin and glycosylated α-DG. The glycosylation of α-DG was considered to be increased by over-expression of fukutin and decreased by knockdown of fukutin. Knockdown of Musashi-1, one of the RNA-binding proteins involved in the regulation of neuronal differentiation, induced a decrease in fukutin mRNA. Immunoprecipitation and ELISA-based RNA-binding assay demonstrated possible binding between fukutin mRNA and Musashi-1 protein. A relationship between fukutin mRNA and vimentin protein was also proposed. In situ hybridization for fukutin mRNA showed a positive cytoplasmic reaction including cytoplasmic processes. From these results, fukutin mRNA is suggested to be a localized mRNA up-regulated by Musashi-1 and to be a component of a mRNA-protein complex which includes Musashi-1 and (presumably) vimentin proteins.

Solitary adenoma in the proventriculus of a budgerigar (Melopsittacus undulatus) diagnosed by immunochemistry — Short communication

The authors describe a solitary adenoma in a 5.5-year-old female Budgerigar (Melopsittacus undulatus). The tumour was partially blocking the lumen of the proventriculus and filled it almost completely. Decreased passage of food towards the gizzard and the intestines developed in the bird as result of the obstruction, which periodically hindered the passage, leading to slow emaciation. An epithelial tumour composed of irregular glandular acini was diagnosed by histological examination. Immunohistochemical reaction with pancytokeratin showed a positive cytoplasmic reaction both in the neoplastic and the normal glandular structures.

Mucin-secreting gastric adenocarcinoma with Rhabdoid areas

Rhabdoid tumor, first described in kidneys of infants and children, is an aggressive tumor that has been reported in several extrarenal locations. In this report, we describe the case of a 40-year-old patient with gastric adenocarcinoma composed of histologically well-differentiated glandular areas and focal rhabdoid zones. The rhabdoid component showed typical features such as abundant eosinophilic cytoplasm, eccentric nuclei, prominent nucleoli and intense focal positive immunohistochemical cytoplasmic reaction for vimentin. Recognition of the rhabdoid phenotype in gastrointestinal tract neoplasms is important because this feature is associated with poor prognosis and unresponsiveness to conventional therapy.

DNA methyltransferase expression in odontogenic cysts and tumours

Epigenetic silencing of gene expression by promoter CpG island hypermethylation is promoted by the enzymes, DNA methyltransferases (DNMTs). DNMT3a is mainly involved in de novo methylation, whereas DNMT1 acts mainly as a maintenance methyltransferase. The purpose of this study was to investigate the immunoexpression of DNMT1 and DNMT3a in a set of odontogenic cysts and tumours. Formalin-fixed and paraffin-embedded tissue samples of eight radicular cysts, 10 odontogenic keratocysts (OKC), eight adenomatoid odontogenic tumours (AOT), 16 ameloblastomas and eight samples of normal mucosae were included in the study. The DNMT1 and DNMT3a proteins were identified by using a highly sensitive polymer-based system. We found that the normal oral mucosa, OKC, AOT, radicular cyst and ameloblastomas samples showed a widespread nuclear and cytoplasmic immunopositivity for DNMT1. Some radicular cysts, ameloblastomas, AOT and OKC samples presented a positive cytoplasmic reaction for DNMT3a, while negative staining was observed in the normal oral mucosa. Nuclear positivity was found only in the suprabasal cell layers of three OKC samples. Our study shows an increased expression of DNMT3a in odontogenic cysts and tumours, confirming that epigenetic mechanisms are involved in the development of these tumours.

Chromophobe renal cell carcinoma and ‘capsulomas’ with acquired cystic disease of the kidney in a long‐term hemodialysis patient

Patients receiving long-term hemodialysis tend to develop renal cell carcinoma (RCC). Among such cases, chromophobe RCC and so-called 'capsulomas' are rarely reported. Here, we report a case of a Japanese woman in her early 70s, who developed both renal lesions after 17 years of hemodialysis. The patient received radical nephrectomy for enlarging renal mass. Grossly, the resected kidney showed a dominant tumor and small-sized subcapsular nodules. Histologically, two types of neoplasm, chromophobe RCC and 'capsuloma', existed with acquired cystic disease of the kidney. Chromophobe RCC had eosinophilic cytoplasm with perinuclear halos, and some tumor cells showed oncocytic features. Hale's colloidal iron staining showed a weakly positive cytoplasmic reaction. Immunohistochemistry was diffusely positive for cytokeratin 7, but negative for vimentin in the tumor cells. 'Capsulomas' were multiple subcapsular nodules composed almost entirely of smooth muscle-like cells with immunoreactivity for melanosome-associated antigen detected by HMB-45.

Expression of caveolar components in primary desminopathy

Myofibrillar myopathies (MFM) involve accumulation of various proteins in the muscle cytoplasm. In myopathy with a heterozygous A337P mutation of the desmin gene, electron-micrographs showed aggregates of vesicular and tubular structures. Positive cytoplasmic reaction for caveolin-3 immunohistochemistry and cholera toxin B binding suggested that caveolae comprised some of the aggregates. As caveolae occur in the Golgi complex and are transported to the cell surface, the results suggest inhibition of their trafficking to the sarcolemma. Alternatively, they could be trapped during internalization. We hypothesize that the accumulation of multiple proteins in MFM could be partially due to inhibited intracellular trafficking.

A Case of Black Thyroid Associated with Hyalinizing Trabecular Tumor

Black thyroid is an uncommon phenomenon of black pigmentation of thyroid parenchyma induced by chronic minocycline therapy. Thyroid tumors associated with black pigmented thyroid are rare. We describe here a 42-year-old woman with a black thyroid associated with hyalinizing trabecular tumor (HTT). The patient presented with a palpable left-sided thyroid nodule. She had taken minocycline for aphthous stomatitis and an oral ulcer for 9 years. The findings of fine needle aspiration biopsy and BRAF mutation analysis suggested a papillary carcinoma. The patient underwent a near-total thyroidectomy with central compartment node dissection. The surgical specimen showed a diffuse black thyroid and a 2-cm non-pigmented, well-circumscribed nodule in the left thyroid. Histopathologically, numerous black pigmented follicular epithelial cells and colloid were seen throughout the thyroid parenchyma, and the nodule was composed of elongated, polygonal cells in trabecular arrangement and dense hyaline stromas. The tumor cells showed a strong positive cytoplasmic reaction to Ki 67. All of these findings suggested a HTT, or a hyalinizing trabecular variant of papillary carcinoma, arising in a black thyroid. To our knowledge, this is the first case of black thyroid associated with HTT.

Secretory activity in medullary thyroid carcinoma: A cytomorphological and immunocytochemical study

Medullary thyroid carcinoma (MTC) is a relatively rare thyroid malignancy of C-cell origin that secretes calcitonin. Although its varied cytomorphologic features are well described in literature, very little is mentioned about the morphologic manifestation of its secretory activity. This study, based on nine fine needle aspiration (FNA) samples from eight MTC patients, is an attempt to present the varied cytomorphologic features suggesting secretory activity in MTC as observed in Papanicolaou and MGG stained FNA smears and correlate them with the immunocytochemical (ICC) staining for calcitonin performed on FNA smears and the serum calcitonin values. The average number of cells in these nine samples was as follows: oval/triangular/plasmacytoid (56.7%), small round (23.6%), spindle-shaped (12.7%), and miscellaneous (7.1%). The cytomorphological features suggesting secretory activity, viz., fine cytoplasmic vacuoles, azurophillic granules, marginal vacuoles, and intracytoplasmic lumina (ICL) with secretions were present in eight, eight, five, and six samples, respectively. Material likely to be amyloid, based on morphological features, was present extracellularly in three samples and both intracellularly and extracellularly in six samples. Immunocytochemically, all the nine samples stained for calcitonin and all the three stained for chromogranin showed positive cytoplasmic reaction in the neoplstic cells. The background amyloid (in six samples), the coarse cytoplasmic granules (in two samples), and the contents of ICL (in one sample) were found to be positively stained for calcitonin. The intracytoplasmic secretory material appeared to be diffusing out of some cells both in the routine MGG stained smears and in the smears stained for calcitonin. Histopathology reports of seven samples in six patients confirmed the cytodiagnosis of MTC in all. Baseline serum calcitonin values in three cases and postoperative serum calcitonin levels during follow-up in three others were high. Thus, our study highlighted the morphological manifestations of secretory activity in MTC and the nature of secretory material as calcitonin, supported by immunocytochemical staining and serum calcitonin level.