Primary Hyperplasia Research Articles

Syndromic MEN1 Parathyroid Adenomas Consist of Both Subclonal Nodules and Clonally Independent Tumors

Abstract Background Primary hyperparathyroidism with parathyroid tumors is a characteristic presentation in Multiple Endocrine Neoplasia Type 1 (MEN1), historically referred to as "primary hyperplasia." The question of whether these tumors signify a multi-glandular clonal disorder or hyperplasia remains inconclusive. Loss of Menin protein expression serves as a reliable surrogate marker for biallelic inactivation and indicates a mutation in the MEN1 gene. The cyclin-dependent kinase inhibitor 1B (CDKN1B) gene, associated with MEN4, encodes the p27 protein, whose expression is inadequately explored in the context of syndromic MEN1. Aims The aim was to explore the molecular basis of syndromic MEN1 parathyroid adenomas, identifying hyperplasia, multiple independent clones, and the extent of Menin loss. Additionally, p27 expression was assessed to evaluate its potential in indicating a germline mutation, especially in distinguishing MEN4 as a clinical alternative to MEN1. Methods In this investigation, we examined histomorphology and protein expression of Menin and p27 in parathyroid adenomas from 25 patients in two independent, well-characterized MEN1 cohorts. Loss of heterozygosity (LOH) patterns were evaluated using fluorescence in situ hybridization (FISH) in one MEN1-associated parathyroid adenoma. Furthermore, next-generation sequencing (NGS) was conducted on eleven nodules from four MEN1 patients. Results Morphologically, the majority of MEN1 adenomas displayed multiple distinct nodules, characterized by predominantly lost Menin expression and reduced p27 protein expression. FISH analysis indicated that most nodules exhibited MEN1 loss, with or without centromere 11 loss. NGS demonstrated both subclonal evolution and the existence of clonally unrelated tumors. Conclusion Syndromic MEN1 parathyroid adenomas, therefore, consist of multiple clones with subclones, aligning with the current framework of the novel WHO classification of parathyroid tumors (2022). The observed loss of p27 expression in a significant fraction of MEN1 parathyroids emphasizes the need for caution when inferring MEN4 solely based on p27 expression.

Syndromic MEN1 parathyroid adenomas consist of both subclonal nodules and clonally independent tumors

Primary hyperparathyroidism with parathyroid tumors is a typical manifestation of Multiple Endocrine Neoplasia Type 1 (MEN1) and is historically termed “primary hyperplasia”. Whether these tumors represent a multi-glandular clonal disease or hyperplasia has not been robustly proven so far. Loss of Menin protein expression is associated with inactivation of both alleles and a good surrogate for a MEN1 gene mutation. The cyclin-dependent kinase inhibitor 1B (CDKN1B) gene is mutated in MEN4 and encodes for protein p27 whose expression is poorly studied in the syndromic MEN1 setting.Here, we analyzed histomorphology and protein expression of Menin and p27 in parathyroid adenomas of 25 patients of two independent, well-characterized MEN1 cohorts. The pattern of loss of heterozygosity (LOH) was assessed by fluorescence in situ hybridization (FISH) in one MEN1-associated parathyroid adenoma. Further, next-generation sequencing (NGS) was performed on eleven nodules of four MEN1 patients.Morphologically, the majority of MEN1 adenomas consisted of multiple distinct nodules, in which Menin expression was mostly lost and p27 protein expression reduced. FISH analysis revealed that most nodules exhibited MEN1 loss, with or without the loss of centromere 11. NGS demonstrated both subclonal evolution and the existence of clonally unrelated tumors.Syndromic MEN1 parathyroid adenomas therefore consist of multiple clones with subclones, which supports the current concept of the novel WHO classification of parathyroid tumors (2022). p27 expression was lost in a large fraction of MEN1 parathyroids and must therefore be used with caution in suggesting MEN4.

PREVALENCE OF BENIGN THYROID LESIONS AMONG ALL GOITRE AT TERTIARY CARE CENTRE GWALIOR

Background: Thyroid gland is a specialized endocrine organ which has various functions in our body, and it is essential for our survival and metabolic functions. Thyroid hormone has various effects in catabolism of carbohydrate and lipid with synthesis of various proteins whose nal outcome is increased BMR. Fine Needle Aspiration Cytology (FNAC) is the commonly used diagnostic technique in thyroid lesions. FNAC of thyroid is the easiest, simple and economical method to assess the diagnosis. Our study is about the prevalence of benign thyroid lesion in all the goitre. To study the spectrum of Aims and Objectives: benign thyroid lesions among all the goitre. This is a 6 year retrospective study which was carried out in cytopat Material and methods: hology section in Department of Pathology from January 2013 to December 2018. Total 866 patients with palpable thyroid swellings were included in the study. The smears made from the aspirate were air dried and stained with May-Grunwald-Giemsa (MGG) stain. Result: Benign lesions in goitre were more common in females. The average age group was found to be 35 years. Out of 866 cases most common thyroid lesion was Colloid goitre 60.97% (n=528), followed by Follicular Neoplasm 10.62% (n=92), Benign cystic lesion 9.47% (n=82) Hashimoto thyroiditis 8.54% (n=74), Malignant lesion 5.43% (n=47), Granulomatous thyroiditis 2.31% (n=20), Primary hyperplasia of thyroid 2.08% (n=18) and 0.58% (n=5) was unsatisfactory. Goitre Conclusion: is common in females than males. Colloid goitre is the commonest thyroid lesion. FNAC is almost an accurate technique for diagnosing thyroid lesions and probable accurate line of management.

Diverse MicroRNAs-mRNA networks regulate the priming phase of mouse liver regeneration and of direct hyperplasia.

ObjectivesAdult hepatocytes are quiescent cells that can be induced to proliferate in response to a reduction in liver mass (liver regeneration) or by agents endowed with mitogenic potency (primary hyperplasia). The latter condition is characterized by a more rapid entry of hepatocytes into the cell cycle, but the mechanisms responsible for the accelerated entry into the S phase are unknown.Materials and methodsNext generation sequencing and Illumina microarray were used to profile microRNA and mRNA expression in CD‐1 mice livers 1, 3 and 6 h after 2/3 partial hepatectomy (PH) or a single dose of TCPOBOP, a ligand of the constitutive androstane receptor (CAR). Ingenuity pathway and DAVID analyses were performed to identify deregulated pathways. MultiMiR analysis was used to construct microRNA‐mRNA networks.ResultsFollowing PH or TCPOBOP we identified 810 and 527 genes, and 102 and 10 miRNAs, respectively, differentially expressed. Only 20 genes and 8 microRNAs were shared by the two conditions. Many miRNAs targeting negative regulators of cell cycle were downregulated early after PH, concomitantly with increased expression of their target genes. On the contrary, negative regulators were not modified after TCPOBOP, but Ccnd1 targeting miRNAs, such as miR‐106b‐5p, were downregulated.ConclusionsWhile miRNAs targeting negative regulators of the cell cycle are downregulated after PH, TCPOBOP caused downregulation of miRNAs targeting genes required for cell cycle entry. The enhanced Ccnd1 expression may explain the more rapid entry into the S phase of mouse hepatocytes following TCPOBOP.

MicroRNA expression signature and target prediction in familial and sporadic primary macronodular adrenal hyperplasia (PMAH)

BackgroundPrimary macronodular adrenal hyperplasia (PMAH), previously termed ACTH-independent macronodular adrenal hyperplasia (AIMAH), is a rare cause of Cushing’s syndrome usually characterized by functioning adrenal macronodules and increased cortisol production.MethodsTo screen and analyse the microRNA (miRNA) profile of PMAH in order to elucidate its possible pathogenesis, a miRNA microarray was used to test tissue samples from patients with familial PMAH, patients with sporadic PMAH and normal control samples of other nontumour adrenocortical tissues and identify characteristic microRNA expression signatures. Randomly selected miRNAs were validated by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). Furthermore, the key signalling pathways and miRNAs involved in PMAH pathogenesis were determined by gene ontology and pathway analysis.ResultsCharacteristic microRNA expression signatures were identified for patients with familial PMAH (16 differentially expressed microRNAs) and patients with sporadic PMAH (8 differentially expressed microRNAs). The expression of the selected miRNAs was confirmed by qRT-PCR, suggesting the high reliability of the miRNA array analysis results. Pathway analysis showed that the most enriched pathway was the renal cell carcinoma pathway. Overexpression of miR-17, miR-20a and miR-130b may inhibit glucocorticoid-induced apoptosis in PMAH pathogenesis.ConclusionWe identified the miRNA signatures in patients with familial and sporadic PMAH. The differentially expressed miRNAs may be involved in the mechanisms of PMAH pathogenesis. Specific miRNAs, such as miR-17, miR-20a and miR-130b, may be new targets for further functional studies of PMAH.

Repression of differentiation genes by Hes transcription factors fuels neural tumour growth in Drosophila.

Neural stem cells (NSC) in divide asymmetrically to generate one cell that retains stem cell identity and another that is routed to differentiation. Prolonged mitotic activity of the NSCs gives rise to the plethora of neurons and glial cells that wire the brain and nerve cord. Genetic insults, such as excess of Notch signaling, perturb the normal NSC proliferation programs and trigger the formation of NSC hyperplasias, which can subsequently progress to malignancies. Hes proteins are crucial mediators of Notch signaling, and in the NSC context they act by repressing a cohort of early pro-differentiation transcription factors. Downregulation of these pro-differentiation factors makes NSC progeny cells susceptible to adopting an aberrant stem cell program. We have recently shown that Hes overexpression in Drosophila leads to NSC hyperplasias that progress to malignant tumours after allografting to adult hosts. We have combined genetic analysis, tissue allografting and transcriptomic approaches to address the role of Hes genes in NSC malignant transformation. We show that the E (spl) genes are important mediators in the progression of Notch hyperplasias to malignancy, since allografts lacking the E (spl) genes grow much more slowly. We further present RNA profiling of Hes-induced tumours at two different stages after allografting. We find that the same cohort of differentiation-promoting transcription factors that are repressed in the primary hyperplasias continue to be downregulated after transplantation. This is accompanied by an upregulation of stress-response genes and metabolic reprogramming. The combination of dedifferentiation and cell physiology changes most likely drive tumour growth.

A novel nonsense mutation in ARMC5 causes primary bilateral macronodular adrenocortical hyperplasia

BackgroundPrimary bilateral macronodular adrenocortical hyperplasia (PBMAH) is a rare form of adrenal Cushing’s syndrome. The slowly progressing expansion of bilateral adrenal tissues usually persists for dozens of years, leading to delayed onset with severe conditions due to chronic mild hypercortisolism. About 20–50% cases were found to be caused by inactivating mutation of armadillo repeat-containing protein 5 (ARMC5) gene.Case presentationA 51-year-old man was admitted for severe diabetes mellitus, resistant hypertension, centripedal obesity and edema. PBMAH was diagnosed after determination of adrenocorticotropic hormone and cortisol levels, dexamethasone suppression tests and abdominal contrast-enhanced CT scanning. The metabolic disorders of the patient remarkably improved after sequentially bilateral laparoscopic adrenalectomy combined with hormone replacement. Sanger sequencing showed germline nonsense mutation of ARMC5 c.967C>T (p.Gln323Ter). The second somatic missense mutation of ARMC5 was detected in one out of two resected nodules, reflecting the second-hit model of tumorigenesis. Routine genetic testing in his apparently healthy offspring showed one of two daughters and one son harbored the germline mutation.ConclusionsIn conclusion, our case report highlight the importance of genetic testing in the molecular diagnosis of PBMAH. Genetic screening in related family members will find out asymptomatic variant carriers to guide life-long follow-up.

SAT-341 Hyperparathyroid Crisis Precipitated by Rapid Correction of Symptomatic Hypercalcemia in an Occult Ectopic Parathyroid Adenoma

Background: Parathyroid adenomas (PA) are typically benign, slow-growing tumors causing gradual increase in parathyroid hormone (PTH) and serum calcium (s.Ca) levels. Hyperparathyroid crisis is a rare and potentially fatal syndrome, which occurs due to rapid elevation of PTH and s.Ca levels (s.Ca >15mg/dL). This can potentiate severe metabolic derangements, manifesting as altered mental status (AMS), renal insufficiency and cardiac arrhythmias. We present a case of hyperparathyroid crisis in the setting of an occult ectopic parathyroid adenoma.Case: 75 year old female with a medical history of osteoporosis, hypertension and Parkinson’s disease, presented to our hospital with AMS and one week history of diarrhea. She was recently hospitalized for pneumonia and treated with antibiotics. Biochemical analysis revealed corrected s.Ca 15.4mg/dL (8.2- 9.6mg/dL; 7 days prior s.Ca was 9.7mg/dL), renal insufficiency (Cr 2.26mg/dL; baseline 1.2) with normal serum phosphorus, magnesium, 25-hydroxyvitamin D and alkaline phosphatase. PTH was found to be elevated at 75pg/mL (15-65pg/mL). She was treated with aggressive intravenous hydration and calcitonin 200mg BID for 3 days. Her s.Ca appropriately trended down. However, her PTH level continued to rise: 319pg/mL 12 hours later, 591pg/mL on day 2 and peaked to 1,242pg/mL on day 3. CT angiography neck showed an incidental finding of a heterogeneous, possibly necrotic, soft tissue nodule in the left paraesophageal region. Additional work-up with technetium 99 Sestamibi scan revealed persistent activity in the upper tracheoesophageal groove consistent with an ectopic PA. She underwent parathyroid exploration with excision of an enlarged ectopic left superior parathyroid adenoma, confirmed on histopathological analysis. The remaining parathyroid glands were normal. PTH declined to 34pg/mL postoperatively. Her mental status improved significantly returning to baseline within a few days with normal PTH and s.Ca levels.Discussion: Secretion of PTH is mediated by s.Ca via the calcium sensing receptors (CaSR). Studies have shown that patients with PA have decreased expression of the CaSR leading to an autonomous rise in PTH secretion and a higher PTH-calcium set point. In our case, the patient initially presented with a mildly elevated PTH level and symptomatic hypercalcemia. The rapid correction of s.Ca levels precipitated a remarkable rise in PTH levels. We postulate that this was caused by a possible upregulation mechanism in calcium sensing by adenomatous parathyroid tissue that is responsive to acute lowering of s.Ca levels, triggering a hyperparathyroid crisis.Reference: (1) Corbetta S., et al. Calcium-sensing receptor expression and signaling in human parathyroid adenomas and primary hyperplasia. Clinical Endocrinology. 2000; 52(3):339-48.

Abstract #806595: Primary Hypothyroidism and Thyrotroph Hyperplasia Progressing to Panhypopituitarism

Abstract #806595: Primary Hypothyroidism and Thyrotroph Hyperplasia Progressing to Panhypopituitarism

Assessment of vital organ histopathology and plasma oxidative conditions of rainbow trout Oncorhynchus mykiss reared in earthen saltwater pond

The aim of this study was to compare gill, kidney, liver and gut histopathology, and plasma antioxidant markers of rainbow trout Oncorhynchus mykiss reared in saltwater earthen ponds in Gomishan, Iran. To this, 10000 fish were distributed in a three-ha earthen pond and 150 fish in three fiberglass tanks (2000L). Blood samples were taken after 3 months rearing with same commercial feed. The source of fish and feed was similar between the saltwater pond and fiberglass tanks. After the 3-month rearing, gill, kidney, liver and gut samples were taken from the pond fish; whereas, blood samples were taken from both the pond and tank fish. There was no significant difference in water temperature, dissolved oxygen and pH between the pond and tanks; however, water salinity and ammonia was higher in the pond compared to the tanks. Plasma superoxide dismutase and glutathione peroxidase activity of the fish in earthen ponds were significantly higher than those fish reared in fiberglass tanks; however, there was no significant in thiobarbituric acid reactive substances between the pond and tanks. The fish had various histopathological symptoms including primary and lamella hyperplasia, lamellar fusion and epithelial lifting. In the kidney section, the fish showed glomerulus shrinkage and/or disappearance, melanomacrophage aggregates and hematopoietic tissue necrosis. These fish showed necrosis and melanomacrophage aggregates in liver and goblet cell hypertrophy in gut. The results suggest that the fish in the earthen pond faced stressful conditions, which might be due to water salinity and ammonia; however, other possible factors, such as pollutants and different feeding regimen must be considered.

Morphological criteria for diagnosis of primary hyperparathyroidism

The work performed on the operating material. A morphological study of the parathyroid glands removed in 128 patients with hyperparathyroidism was performed. For the histological study pieces of the parathyroid gland were taken. The pieces were fixed in 10 % buffered formalin for 10 days, then washed in running water, passed through a processor and embedded in paraffin. From paraffin blocks, sections of 5–6 µm were prepared. Sections were stained with hematoxylin and eosin, pikrofuksin according to Van Gieson, toluidine blue, according to Mallory, used CHIC-reaction. The results of the study showed that primary hypothyroidism is more common in women (82 %) aged 41–50 years (42.2 %). The size of the parathyroid glands ranged from 0.3 to 8.2 cm. Adenomas were found in 51.6 % of patients, hyperplasia in 43.0 %, cancer in 5.4 % of them. In primary hyperplasia, there is an increase in all parathyroid glands, upper pair or lower pair. Upper pairs are increased more. Histological examination indicates lobular structure of the gland, lobular hyperplasia, diffuse proliferation of the main, acidophilic and transitional forms of parathyrocytes, monomorphic structure, reduction or absence of stromal fat, the presence of a large number of vessels. Hyperplasia of the main cells was detected in 67 % of patients, hyperplasia of acidophilic cells in 28 %, hyperplasia of light cells in 3 %, mixed hyperplasia in 2 % of them.

Parathyroid Neoplasms: Immunohistochemical Characterization and Long Noncoding RNA (lncRNA) Expression.

Parathyroid adenomas are slow growing benign neoplasms associated with hypercalcemia, while atypical parathyroid adenomas and parathyroid carcinomas are uncommon tumors and their histologic features may overlap with parathyroid adenomas. LncRNAs participate in transcription and in epigenetic or post-transcriptional regulation of gene expression, and probably contribute to carcinogenesis. We analyzed a group of normal, hyperplastic, and neoplastic parathyroid lesions to determine the best immunohistochemical markers to characterize these lesions and to determine the role of selected lncRNAs in tumor progression. A tissue microarray consisting of 111 cases of normal parathyroid (n= 14), primary hyperplasia (n= 15), secondary hyperplasia (n= 10), tertiary hyperplasia (n= 11), adenomas (n= 50), atypical adenomas (n= 7), and carcinomas (n= 4) was used. Immunohistochemical staining with antibodies against chromogranin A, synaptophysin, parathyroid hormone, and insulinoma-associated protein 1(INSM1) was used. Expression of lncRNAs including metastasis-associated lung adenocarcinoma transcript one (MALAT1), HOX transcript antisense intergenic RNA (HOTAIR), and long intergenic non-protein coding regulator of reprograming (Linc-ROR or ROR) was also analyzed by in situ hybridization and RT-PCR. All of the parathyroid tissues were positive for parathyroid hormone, while most cases were positive for chromogranin A (98%). Synaptophysin was expressed in only 12 cases (11%) and INMS1 was negative in all cases. ROR was significantly downregulated during progression from normal, hyperplastic, and adenomatous parathyroid to parathyroid carcinomas. These results show that parathyroid hormone and chromogranin A are useful markers for parathyroid neoplasms, while synaptophysin and INSM1 are not very sensitive broad-spectrum markers for these neoplasms. LincRNA ROR may function as a tumor suppressor during parathyroid tumor progression.

A retrospective study of the treatment-associated mortality of the patients with primary ocular adnexal mucosa-associated lymphoid tissue lymphoma after the molecular and immunological diagnosis.

e19534Background: Differentiation between primary ocular adnexal mucosa-associated lymphoid tissue (POA-MALT) lymphoma and reactive lymphoid hyperplasias sometimes may be difficult. We have examine...

Nuclear Medicine Methods for Evaluation of Abnormal Parathyroid Glands in Patients with Primary and Secondary Hyperparathyroidism.

Considered rare disease in the past, primary hyperparathyroidism (PHPT) has dramatically increased in incidence over the past thirty years with the introduction of routine calcium measurements; it is now approximately 42 per 100 000 persons. By far, the most common lesion found in patients with PHPT is the solitary parathyroid adenoma, occurring in 85%-90% of patients, while in the rest 10%- 15% primary hyperplasia of the parathyroid glands is present. Currently, the most widely used surgical approach is minimally invasive parathyroidectomy which is associated with less post-surgery complications and shorter operation time. To be successful this procedure needs to rely on a precise preoperative localization of the abnormal parathyroid glands, hence preoperative parathyroid imaging gained so large importance. The rationale for locating abnormal parathyroid tissue prior to surgery is that the glands can be notoriously unpredictable in their location. There is a general consensus that the best imaging procedure identifying abnormal parathyroid glands is the preoperative scintigraphy with 99mTc-sestamibi or 99mTc-tetrofosmin. It is characterized with high sensitivity and specificity exceeding those of ultrasound, CT or MRI. Combining scintigraphy with the other imaging techniques increases the precision for topic localization.

Involvement of ARMC5 in proliferation and cell cycle control of human cell cultures from adrenal nodules of primary macronodular adrenocortical hyperplasia (PMAH)

Involvement of ARMC5 in proliferation and cell cycle control of human cell cultures from adrenal nodules of primary macronodular adrenocortical hyperplasia (PMAH)

A familial adrenal incidentaloma story

Primary macronodular bilateral adrenal hyperplasia (PMBAH) was incidentally identified in a 69-year-old woman who developed a biliary colic. She had a 30-year history of hypertension and was treated by three antihypertensive drugs. Concomitantly, one of her four sons was also referred after incidentally discover of a PMBAH. This 50-year-old man had developed, 1 year before, severe hypertension needing four antihypertensive drugs. Moreover, 2 years before, another son was also incidentally diagnosed for PMBAH through an ampulloma cure. This 49-year-old man had no hypertension but osteoporosis treated for many years. Hormonal evaluation showed in all three patients: basal suppressed ACTH, no plasma cortisol suppression after 1-mg over-night dexamethasone suppression test and aberrant adrenal sensitivity in response to several ligands (all data will be shown on poster). The mother underwent surgical resection of the biliary duct tumor. Histopathology is compatible with a neuroendocrine tumor. Immunostainings and genetic testing are still in progress. PBMAH is often genetically determined and several genes have been identified, ARMC5 being the last one. Illegitimate receptor expression is observed in the majority of PBMAH. However, the associated-tumors phenotype exhibited by this family does not enter into the spectrum of the described malignancies predisposing syndromes (no hyperparathyroidism). Anyway, investigations are continued in the others children and grandchildren. This case illustrates the phenotype variability within one family with a rare genetic cause of Cushing's syndrome and highlights the importance of a complete clinical characterization to permit phenotype-genotype correlations for a better knowledge of this disease.

Mouse Models Recapitulating Human Adrenocortical Tumors: What Is Lacking?

Adrenal cortex tumors are divided into benign forms, such as primary hyperplasias and adrenocortical adenomas (ACAs), and malignant forms or adrenocortical carcinomas (ACCs). Primary hyperplasias are rare causes of adrenocorticotropin hormone-independent hypercortisolism. ACAs are the most common type of adrenal gland tumors and they are rarely “functional,” i.e., producing steroids. When functional, adenomas result in endocrine disorders, such as Cushing’s syndrome (hypercortisolism) or Conn’s syndrome (hyperaldosteronism). By contrast, ACCs are extremely rare but highly aggressive tumors that may also lead to hypersecreting syndromes. Genetic analyses of patients with sporadic or familial forms of adrenocortical tumors (ACTs) led to the identification of potentially causative genes, most of them being involved in protein kinase A (PKA), Wnt/β-catenin, and P53 signaling pathways. Development of mouse models is a crucial step to firmly establish the functional significance of candidate genes, to dissect mechanisms leading to tumors and endocrine disorders, and in fine to provide in vivo tools for therapeutic screens. In this article, we will provide an overview on the existing mouse models (xenografted and genetically engineered) of ACTs by focusing on the role of PKA and Wnt/β-catenin pathways in this context. We will discuss the advantages and limitations of models that have been developed heretofore and we will point out necessary improvements in the development of next generation mouse models of adrenal diseases.

Clinical features and prognosis of conjunctival lymphoid hyperplasia

Background Primary conjunctival lymphoid hyperplasia exhibit atypical clinical symptoms and easy to cause misdiagnosis and mistreatment.Understanding the clinical characteristics of primary conjunctival lymphoid hyperplasia is of an important clinical significance. Objective This study was to analyze the clinical characteristics and therapeutic outcome of patients with primary conjunctival lymphoid hyperplasia. Methods The medical records of 20 patients with primary conjunctival lymphoid hyperplasia who was treated in Beijing Tongren Hospital from January 2012 to December 2014 were retrospectively analyed.The age, symptoms, therapy, prognosis, histopathological features and immonochemistry results were reviewed, and the treating approach targeting to different types of conjunctival lymphoid hyperplasia was evaluated.The fellow-up duration was 1-2 years. Results Age of the patients ranged from 27 to 83 years old.The lesions were classified as benign lymphocytic hyperplasia, atypical lymphoid hyperplasia and lymphoma.Majority of lesions located in fornix conjunctiva tissue (90%). Follicle-like appearance was seen in the benign lymphocytic hyperplasia, and pink elavation was exhibited at the bulbar conjunctiva in the atypical lymphoid hyperplasia.A diffuse salmon fish like appearance in conjunctiva was the primary feature of conjunctival lymphoma.Histopathological examination showed that conjunctival benign lymphocytic hyperplasia had follicle-like tissue in lesions, atypical lymphoid hyperplasia exhibited diffuse lymphocyte filtration, and conjunctival lymphoma appeared monocyte filtration.The 3 tpyes of lesions also could be differentiated by immunochemistry.The medicine was applied in the eyes with benign lymphocytic hyperplasia, and the combination of resection of lesions with conjunctival tissue or amniotic membrane transplantation was used for the atypical lymphoid hyperplasia or lymphoma eyes.No recurrence of the lesions was found during fellow-up duration. Conclusions The clinical manifestations of conjunctival lymphoid hyperplasia lesions are varied, and it is easy to be confused with chronic ocular surface diseases.Pathology and immunochemistry are helpful for the differential diagnosis.The treating regimen is dependent on the lesion type.Most patients have a favorable prognosis with treatment. Key words: Conjunctival diseases/pathology; Conjunctival neoplasms/diagnosis & therapy; Hyperplasia; Lymphoid tissue/pathology; Lymphoma/pathology; Retrospective studies; Humans

Carney complex with PRKAR1A mutation: A case report

Carney complex is a multiple endocrine neoplasia syndrome with various features which include myxomas, endocrine tumours and lentigines lesions. We report a case of Carney complex with components of lentigines, ACTH independent adrenal Cushing’s syndrome (with a paradoxical increase in 24 hour urinary cortisol following the high dose (8mg) dexamethasone suppression test – and is likely to be due to primary pigmented nodular adrenal hyperplasia) positive for a protein kinase A type 1A regulatory subunit (PRKAR1A) gene mutation.

Pathological Investigations on Galilee Tilapia (Sarotherodon galilaeus) Following Chronic Exposure to Cadmium Chloride

The morphopathological alterations of chronic cadmium (Cd) toxicity in Sarotherodon galilaeus were studied. 126 fish were used to determine 96 hrs LC50 of cadmium chloride, the obtained result was 28.3 mg/L. Forty-eight fish were used to induce chronic toxicity, twenty-four fish were exposed to 2.83 mg/L cadmium chloride for 8 weeks and other fish as control. Gills, hepatopancreas, posterior kidney and spleen were the most affected organs during chronic exposure. Eosinophilic granular cells (EGCs) infiltration and goblet cells hyperplasia in tips of primary lamellae, lamellar lifting, lamellar necrosis and Proliferative interlamellar hyperplasia with fusion in gills, hydropic degeneration and necrosis of the hepatic cells, hemorrhage and necrotic renal tubules and splenic necrosis and depletion of lymphocytes were recorded as histopathological changes.