Endocrine Pathology (ENDOCR PATHOL)

Publications in this journal

• Article: Erratum to: Case Report: Adrenal LH/hCG Receptor Overexpression and Gene Amplification Causing Pregnancy-Induced Cushing’s Syndrome

  Michael Herman Chui, Nese Colak Özbey, Shereen Ezzat, Yersu Kapran, Yesim Erbil, Sylvia L. Asa
  Endocrine Pathology 04/2012; 21(2):148-148.
• Article: Telomerase activity in well-differentiated papillary thyroid carcinoma corrrelates with advanced clinical stage of the disease

  Leticia Bornstein-Quevedo, M. L. García-Hernández, Ignacio Camacho-Arroyo, Miguel F. Herrera, Arturo Angeles Angeles, Ofelia González Treviño, Armando Gamboa-Domínguez
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  ABSTRACT: Clinical relevance and stage correlation of telomerase activity in well-differentiated papillary thyroid carcinoma (WD PTC) has not been well determined, as its reported activity could be due to the analysis of tumors with lymphocytic infiltrates or aggressive variants of papillary carcinomas. We conducted a prospective study of telomerase activity in WD PTC without inflammatory infiltrates and correlated it with clinical stage. Fifty WD PTCs were analyzed for telomerase activity by PCR-based TRAP (telomeric repeat amplification protocol) assay. Results were correlated with stage and other clinicopathologic variables. Twenty-one (42%) WD PTCs demonstrated telomerase activity. The enzyme was detected more frequently in stage III/IVa WD PTCs (p=0.02) and in tumors with extra thyroidal extension (p=0.04). The risk of presenting advanced disease (stage III/IVa) and extrathyridal growth was significantly increased in telomerase-positive tumors (p=0.01; odds ratio [OR] 4.4 [95%Cl 1.3–14.7]) and (p=0.04; OR 3.6 [95%Cl 1.1–11.7]), respectively. Also, a correlation was found between telomerase activity and age. There was no correlation of telomerase activity with gender, histologic variant, tumor size, or cervical lymph node metastasis. Telomerase activity was observed in 42% of WD PTC and was detected more frequently in AJCC TNM stage III/IVa cases. This finding suggests that telomerase deregulation could be involved in tumor progression.
  Endocrine Pathology 04/2012; 14(3):213-219.
• Article: Expression of sodium iodide symporter in benign and malignant human thyroid tissues

  Jen-Der Lin, Chuen Hsueh, Tzu-Chieh Chao, Hsiao-Fen Weng
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  ABSTRACT: The extent of human sodium iodide symporter (hNIS) expression in different kinds of human thyroid cancer tissues and cell lines remains controversial. In this study, polyclonal antibodies to hNIS were used to analyze the expression of symporter protein in benign and malignant human thyroid tissues. Formalin-fixed, paraffin wax-embedded tissue sections were used. Staining was performed using primary polyclonal antibody of rabbit anti-human hNIS diluted in PBS (1:500). Results showed that 2 of 3 normal tissue, 3 of nodular hyperplasia, one follicular adenoma, 3 of 11 papillary thyroid carcinoma, 1 of 5 follicular carcinoma and none of 3 metastatic thyroid epithelial tissue specimens stained positively for hNIS. A higher percentage of positive staining for symporter protein was found in benign thyroid tissues including normal thyroid tissue, nodular hyperplasia, and adenoma (60%). In contrast, papillary and follicular thyroid carcinomas demonstrated lower symporter protein expression (20%). In conclusion, although the number of tissue samples examined in this study was small, hNIS staining found a higher ratio of symporter protein expression in normal and benign thyroid tissues compared with malignant tissues. Determination of the reason for discrepancies in the expression of hNIS in in vivo and in vitro studies will require further investigation.
  Endocrine Pathology 04/2012; 12(1):15-21.
• Article: Hürthle cell carcinoma arising from thyroid papillary carcinoma

  L. Jonathan Zwi, Virginia A. LiVolsi
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  ABSTRACT: Hürthle cell carcinoma of the thyroid is generally considered to be a subtype of follicular carcinoma. We report a case of a small solitary usual-type papillary carcinoma of the thyroid, with metastatic tumor in cervical lymph nodes. The lymph node tumor consisted of both tall-cell papillary carcinoma and Hürthle cell carcinoma. This suggests a closer relationship between papillary cell carcinoma and Hürthle cell tumors than previously appreciated.
  Endocrine Pathology 04/2012; 13(3):213-217.
• Article: Proprotein-processing endoprotease furin and its substrate parathyroid hormone-related protein are coexpressed in insulinoma cells

  Yoshie Sawada, Toru Kameya, Toru Aizawa, Tetsuro Izumi, Toshiyuki Takeuchi
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  ABSTRACT: Parathyroid hormone-related protein (PTHrP) is frequently produced in pancreatic endocrine tumors. PTHrP is synthesized as the precursor pro-PTHrP and undergoes a series of posttranslational processing reactions, among which cleavage of a 12 amino acid sequence from its precursor is crucial for the biological activation of PTHrP. This cleavage is catalyzed by furin, a proprotein-processing endoprotease that cleaves the consensus sequence-Arg-X-(Lys/Arg)-Arg ↓ X-. We previously reported that furin is highly expressed in rat pancreatic islets during the perinatal stage and that the expression of furin in pancreatic β cells induces faster cell growth. From this, we postulated that furin may be co-expressed with PTHrP in insulinomas. We immunostained insulin, PTHrP, and furin in 21 human pancreatic endocrine tumors: 10 insulinomas, 5 VIPomas, 4 gastrinomas, and 2 somatostatinomas. Of these 21 endocrine tumors, furin was positively stained in all 10 insulinomas. Likewise, PTHrP was detected in the same insulinomas. We found one VIPoma and one gastrinoma contained a few insulin-positive cells scatteringly, which were also positive for furin and PTHrP. But other non-insulinoma endocrine tumors did not display furin and PTHrP positivity. We conclude that furin and its substrate pro-PTHrP are co-expressed specifically in insulinomas.
  Endocrine Pathology 04/2012; 11(1):31-39.
• Article: Tuberculous granulomatous inflammation associated with adenoma of parathyroid gland manifesting as primary hyperparathyroidism

  Dilip K. Kar, Gaurav Agarwal, Bhavna Mehta, Jyotsna Agarwal, Ramesh K. Gupta, Tapan N. Dhole, Saroj K. Mishra
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  ABSTRACT: A 36-year-old female presented with generalized bone pain, muscular weakness, and enlarged cervical lymph nodes. The biochemical findings and skeletal survey were suggestive of primary hyperparathyroidism (PHPT). CT of neck and thorax showed enlarged multiple lymph nodes in the cervical and superior mediastinal region. With a diagnosis of PHPT, she underwent cervical exploration and excision of enlarged right inferior parathyroid gland, along with biopsy of nodes. Histopathology revealed the features of parathyroid adenoma with a few foci of epithelioid granuloma and granulomatous lymphoadenitis. Smear and culture were negative for AFB. A positive PCR for Mycobacterium tuberculosis of the homogenates of parathyroid tumor confirmed tuberculous inflammation within the parathyroid adenoma. To the best of our knowledge, this is the first reported case of parathyroid adenoma associated with tuberculous pathology in a case of PHPT.
  Endocrine Pathology 04/2012; 12(3):355-359.
• Article: Cushing’s syndrome caused by a well-differentiated Ileal neuroendocrine carcinoma

  Isabelle Valo, Vincent Rohmer, Serge Guyétant, Jean-François Martin, Sophie Venault, Jean-Paul Saint-André
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  ABSTRACT: We report a very rare case of Cushing’s syndrome caused by an ileal adrenocorticotrophin-secreting well-differentiated endocrine carcinoma with liver metastases. A 62-yr-old woman presented with clinical and biological signs suggestive of paraneoplastic Cushing’s syndrome. Radiological investigations, including magnetic resonance imaging of the pituitary gland, chest and abdominal computerized tomography scan, small bowel barium study and pancreatic endoscopic scan, 111-pentetreotide scintigraphy (octreoscan), esogastroduodenoscopy, and colonoscopy did not detect the source of the ectopic adrenocorticotropic hormone (ACTH) secretion but showed a few liver nodules. Because a 10-mo-long ketoconazole treatment was not effective, a bilateral adrenalectomy was performed in order to control the Cushing’s syndrome, and a liver nodule biopsy diagnosed a metastatic neuroendocrine tumor. Subsequently, a second laparotomy disclosed a 1.8 cm ileal neuroendocrine tumor, cosecreting ACTH and serotonin on immunohistochemistry with many liver metastases. ACTH secretion by intestinal neuroendocrine tumors is rare, and the secretion is almost always clinically silent. Cushing’s syndrome caused by an intestinal low-grade neuroendocrine tumor is even rarer, with only two previous cases reported in the literature. Our observation underlines the difficulty of localizing the source of ectopic ACTH secretion in paraneoplastic Cushing’s syndrome.
  Endocrine Pathology 04/2012; 11(4):359-364.
• Article: Expression of p18INK4C is Down-regulated in Human Pituitary Adenomas

  Md. Golam Hossain, Takeo Iwata, Noriko Mizusawa, Zhi Rong Qian, Shahidan Wan Nazatul Shima, Toru Okutsu, Shozo Yamada, Toshiaki Sano, Katsuhiko Yoshimoto
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  ABSTRACT: Cyclin-dependent kinase inhibitors represented by the INK4 family comprising p16INK4A, p15INK4B, p18INK4C, and p19INK4D are regulators of the cell cycle shown to be aberrant in many types of cancer. Mice lacking p18Ink4c exhibit a series of phenotypes including the development of widespread organomegaly and pituitary adenomas. The objective of our study is to examine the role of p18INK4C in the pathogenesis of human pituitary tumors. The protein and mRNA levels of p18INK4C were examined by immunohistochemistry and real-time reverse transcription-polymerase chain reaction, respectively. The methylation status of the p18INK4C gene promoter and somatic mutations of the p18INK4C gene were also investigated. p18INK4C protein expression was lost or significantly reduced in 64% of pituitary adenomas compared with levels in normal pituitary glands. p18INK4C mRNA levels were low in all ACTH adenomas and non-functioning (NF)-FSH and in 42%, 70% and 66% of GH, PRL, and subtype 3 adenomas, respectively. p18INK4C mRNA levels were significantly associated with p18INK4C protein levels. Neither methylated promoters in pituitary adenomas, except in one NF-FSH adenoma, nor somatic mutations of the p18INK4C gene in any pituitary adenomas were detected. The down-regulation of p18INK4C expression may contribute to the tumorigenesis of pituitary adenomas.
  Endocrine Pathology 04/2012; 20(2):114-121.
• Article: Differential diagnosis of pheochromocytomas and paragangliomas

  Anne Marie McNicol
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  ABSTRACT: Paragangliomas are of two types, sympathetic and parasympathetic, depending on the type of paraganglion in which they arise. The term pheochromocytoma is reserved for tumors arising in the adrenal medulla. These tumors are usually fairly easy to diagnose. However, several areas are the subject of debate, including the identification of malignant potential, the diagnosis of medullary hyperplasia, and the recognition of composite tumors. Some histologic features can cause problems in differential diagnosis. Paragangliomas may have spindle cell morphology or contain pigment, requiring distinction from mesenchymal tumors and melanoma, respectively. Extensive degenerative change in phenochromocytomas may mimic adrenal cortical tumors. This short review addresses the diagnosis of pheochromocytomas and paragangliomas and discusses useful approaches in the aforementioned problem areas.
  Endocrine Pathology 04/2012; 12(4):407-415.
• Article: Juvenile rheumatoid arthritis with amyloid goiter: Report of a case with review of the literature

  Amitabh Srivastava, Mukta Baxi, Subhash Yadav, Amit Agarwal, Ramesh K. Gupta, Saroj K. Misra, Ambrish Mithal
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  ABSTRACT: Clinically significant enlargement of the thyroid owing to amyloid deposition is a rare occurrence. A 23-yr-old female, a case of juvenile rheumatoid arthritis, developed rapidly increasing thyromegaly during the course of her illness with complaints of dyspnea and dysphagia. Thyroid function tests were within normal limits. Fine-needle aspiration cytology proved inconclusive. Total thyroidectomy was done for symptomatic relief with a preoperative clinical impression of malignancy. Histopathologic findings were consistent with amyloid goiter. The findings of this case are presented, to emphasize the difficulties in making a definite preoperative diagnosis, along with a brief review of the literature.
  Endocrine Pathology 04/2012; 12(4):437-441.
• Article: Papillary carcinoma occurring within an adenomatous goiter of the thyroid gland in Cowden's disease

  Kaori Kameyama, Hiroshi Takami, Kuniharu Miyajima, Takashi Mimura, Yasuhiro Hosoda, Kunihiko Ito, Koichi Ito
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  ABSTRACT: Cowden's disease is an autosomal dominant disorder characterized by multiple benign and malignant neoplastic lesions involving many organs. The presence of characteristic cutaneous lesions is crucial for the diagnosis. Thyroid disease is a major extracutaneous manifestation of this disease; however, the histologic characteristics have not been described in detail. We report a case of thyroid tumor associated with Cowden's disease. Grossly, the tumor showed a multinodular appearance, like an adenomatous goiter. Microscopically, it consisted of follicular adenomas with a trabecular pattern. Some of the nodules had a second component resembling papillary carcinoma. This was thought to be a unique histological feature not described previously, and might be specific to thyroid tumor associated with Cowden's disease.
  Endocrine Pathology 04/2012; 12(1):73-76.
• Article: Expression of hepatocyte growth factor (HGF) and its receptor (MET) in medullary carcinoma of the thyroid

  Mauro Papotti, Martina Olivero, Marco Volante, Francesco Negro, Maria Prat, Paolo M. Comoglio, Maria Flavia DiRenzo
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  ABSTRACT: The tyrosine kinase receptor encoded by the MET oncogene has the unusual property of mediating the invasive growth of epithelial cells upon binding with the hepatocyte growth factor (HGF). The MET/HGF receptor is known to be overexpressed in thyroid carcinomas originated from follicular cells, but has not been reported in C cell tumors. To investigate the role of HGF and of its receptor (encoded by MET oncogene) in medullary carcinoma of the thyroid (MCT), we studied the expression of HGF and MET in 20 cases by means of different techniques. By RT-PCR, HGF mRNA was found in 10/20 cases, while MET mRNA presence was demonstrated in 8/20, of which 7 also expressed HGF. Northern blot analysis and in situ hybridization were performed in selected cases and confirmed RT-PCR data in some cases, although the lower sensitivity of these procedures did not allow the identification of all RT-PCR positive cases. By immunohistochemistry (using specific monoclonal antibodies) HGF was demonstrated in 8/9 RT-PCR positive cases ald a monoclonal to MET immunostained 5/6 RT-PCR positive cases. All receptor positive cases also expressed the ligand in the same tumor cell population. These findings demonstrate MET and HGF co-expression in a subset of MCT, in which autocrine/paracrine circuits may be active. No correlation was found between HGF/MET expression and clinico-pathological parameters, except for the more common multifocality of HGF/MET positive MCT. Whether the potential activation of MET in MCT is responsible for local invasion and malignant evolution is to be further investigated, especially in multifocal and aggressive tumors.
  Endocrine Pathology 04/2012; 11(1):19-30.
• Article: p53/MDM2 pathway aberrations in parathyroid tumors: p21WAF-1 and MDM2 are frequently overexpressed in parathyroid adenomas

  Begoña Arribas, Eva Cristóbal, José A. Alcázar, Juan Tardío, Juan C. Martínez-Montero, José R. Polo, Rafael Carrión, Laura Gil, Marta Azañedo, José M. Rojas, Javier Menárguez
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  ABSTRACT: Parathyroid adenomas (PTAs) are the main cause of primary hyperparathyroidism. Cell cycle regulation in normal parathyroid tissue (NPT) and PTA remains largely unknown. We have systematically explored several components involved in the p53/MDM2/p19ARF pathway in PTA and compared the results were with NPT. Forty-six PTA and 12 NPT were immunostained with anti-p21WAF-1, MDM2, p53, and p27KIP1 antibodies. The slides were processed by cytometry and the results were statistically analyzed using nonparametric methods (Mann-Whitney test). p21WAF-1 and MDM2 expression were significantly higher in PTA compared with NPT (p<0.05). The opposite results were found for p27KIP1 (p<0.05). Occasional p53 staining was found in some PTA, albeit no significant difference was found in comparison with NPT. In conclusion, MDM2 and p21WAF-1 are the proteins more overexpressed in PTA. These findings are surprising taking into account the benign nature of PTA, making them suitable candidates for further molecular analysis.
  Endocrine Pathology 04/2012; 11(3):251-257.
• Article: Clinicopathological Characterization of TSH-Producing Adenomas: Special Reference to TSH-immunoreactive but Clinically Non-functioning Adenomas

  Elaine Lu Wang, Zhi Rong Qian, Shozo Yamada, Md Mustafizur Rahman, Naoko Inosita, Teruyoshi Kageji, Hideko Endo, Eiji Kudo, Toshiaki Sano
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  ABSTRACT: Thyrotropin (thyroid-stimulating hormone (TSH))-producing pituitary adenomas have been known to be quite variable in clinical features covering from typical functioning TSH-producing adenomas (FTSHomas) associated with hyperthyroidism to clinically silent TSH cell adenomas (STAs) that are apparently unassociated with hyperthyroidism. It is important to distinguish STAs from other types of clinically non-functioning adenomas for adequate postoperative managements. However, because of rareness of TSH-producing adenomas, their histopathological features linking to the clinical manifestations have not been well characterized. Herein, we investigated clinical and histopathological findings to characterize 29 TSH-producing adenomas including 20 FTSHomas and nine STAs. Clinical symptoms of the patients with STAs included headache, visual defect, vertigo, and nausea. All STAs and 19 FTSHomas were macroadenoma. The average tumor size of STAs was significantly larger than that of FTSHomas (P < 0.05). The invasiveness was detected in 33% STAs and in 20% FTSHomas. Both STAs and FTSHomas showed a variety of morphological features and immunohistochemical profiles. Chromophobic polygonal or short-spindled tumor cells usually proliferated in a diffuse pattern, while they exhibited globoid or whorl-like appearance with intertwined cytoplasmic processes in both subgroups. Stromal fibrosis and calcification were often noted. Their nuclei were somehow pleomorphic. Ultrastructural features of all four STAs examined were similar to those of normal thyrotrophs. Thus, STAs and FTSHomas were indistinguishable by histology alone. Immunohistochemically, the number of TSH-positive cells in individual FTSHomas was highly various. Six tumors showed only a few TSH-positive cells (1–5%), and three were negative for TSH by conventional method without antigen retrieval. After proteinase K treatment, these tumors turned out TSH positive. As defined, STAs were TSH positive in more than 20% of tumor cells and three of them in more than 50%. Growth hormone- and/or prolactin-positive cells were detected in 55% STAs and 63% FTSHomas. Both pituitary-specific transcription factor 1 and GATA-binding protein 2 were expressed in all STAs and 20 FTSHomas. Membranous somatostatin receptor (SSTR)-2A immunoreactivity was found in 89% STAs and 94% FTSHomas, whereas SSTR5 was positive in 78% of both STAs and FTSHomas. MIB-1 labeling index was related to tumor invasiveness and tumor size (P < 0.05, P = 0.09, respectively). Thus, although both STAs and FTSHomas showed unique histopathological features distinct from other type adenomas, these two subgroups were indistinguishable by histopathology. Immunohistochemistry for TSH by use of antigen retrieval, transcription factors, and SSTRs may be useful to confirm STAs and to determine the postoperative therapy among various kinds of clinically non-functioning adenomas.
  Endocrine Pathology 04/2012; 20(4):209-220.
• Article: Autopsy findings in diabetic patients: A 27-Yr clinicopathologic study with emphasis on opportunistic infections and cancers

  King-Yin Lam
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  ABSTRACT: Diabetes mellitus has become a growing epidemic in the Asia-Pacific region. The aims of this study were to determine at autopsy the prevalence and characteristics of pathologic lesions in patients with diabetes mellitus. The 13,215 autopsy reports in our institution were examined for the diagnosis of diabetes mellitus. In patients with diabetes mellitus, the demographic data and the different pathologic lesions noted were analyzed. Diabetes mellitus was found in 820 patients (426 men and 394 women), comprising 6.2% of all autopsies. The two most common types of disease were cardiovascular diseases and infections, found in 69 and 53% of diabetic patients, respectively. Bacterial infection, in particular tuberculosis, was the most common type of infection noted. Localized and disseminated fungal infections were also common. In addition, urinary tract diseases were noted in 48%, hepatobiliary tract lesions in 42%, central nervous system disorders in 25%, and tumors in 29% of the diabetic patients. Malignant tumors were more often seen than benign tumors (18 vs 11% of patients, respectively). Many of the tumors were adenocarcinomas, and the most common neoplastic lesions were carcinomas of the lung, pancreas, liver, large intestine, stomach, and esophagus. Diabetic complications and associated diseases are common problems in this population. Adequate health care resources are needed for their prevention and treatment.
  Endocrine Pathology 04/2012; 13(1):39-45.
• Article: Morphological analysis of adrenal glands: A prospective analysis

  King-Yin Lam, Alexander Chak-Lam Chan, Chung-Yau Lo
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  ABSTRACT: There is a lack of studies to document the weight range of normal adrenal glands. The aims of the current study are to find out the weight range of normal adrenal glands in Chinese patients and to analyze any potential factors affecting it. Adrenal glands not affected by disease were prospectivelly collected from autopsies on 333 Chinese patients (208 men, 125 women). The weight and longest dimension of each adrenal gland were noted. The impact of various clinicopathological factors on the adrenal weight was studied. In addition, the morphometric features of these adrenal glands were compared with that of 28 surgically resected adrenal glands with cortical adenomas. The mean combined weight of adrenal glands was 11.8 g (range=5.8 g to 19.9 g). The left adrenal gland was often heavier than the right (mean weight=6.1 g and 5.7 g respectively) and with a greater longitudinal length than the right (mean length=5.2 cm and 4.8 cm respectively). Adrenal glands were often heavier in male, younger age group (less than 60-yr-old) and patients with history of hypertension or lung cancers. In comparison, the mean weight of right adrenal gland with cortical adenoma was 11.7 g (range=6 g to 26 g) and that of left adrenal gland with cortical adenoma was 9.4 g (range=4.6 g to 25 g). This is the first study in the English literature that provides data on the weight of normal adrenal glands in a solely Chinese population. Adrenal weight may be affected by patients' gender, age, laterality of adrenal gland and presence of systemic disease.
  Endocrine Pathology 04/2012; 12(1):33-38.
• Article: Sporadic type composite pheochromocytoma with neuroblastoma: Clinicomorphologic, DNA content, and ret gene analysis

  Fernando A. Candanedo-González, Isabel Alvarado-Cabrero, Armando Gamboa-Domínguez, Arturo Cérbulo-Vázquez, Ricardo López-Romero, Leticia Bornstein-Quevedo, Mauricio Salcedo-Vargas
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  ABSTRACT: Composite pheochromocytomas (CP) account for only 3% of all pheochromocytomas. We analyzed the clinical, immunohistochemical, ultrastructural, DNA content, and a 634 ret mutation feature in a 56-yr-old Mexican woman with a CP localized in the right adrenal gland and associated with a blood pressure of 140/90 mmHg. Clinical symptoms were absent after surgery. The tumor showed pheochromocytoma and neuroblastoma components. This dual phenotype was supported by light microscopy and corroborated by immunohistochemistry and ultrastructural findings. Flow cytometric analysis showed that both components were diploid. A genetic mutational analysis of the ret oncogene in exon 11 showed no 634 mutation. This case demonstrates the indolent behavior of neuroblastoma associated with a sporadic-type CP in an adult patient.
  Endocrine Pathology 04/2012; 12(3):343-350.
• Article: Neurofilaments in thyrotrophs of hypothyroid rats: An immunohistochemical study

  Eva Salinas, J. Luis Quintanar
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  ABSTRACT: We examined by immunohistochemistry the expression of 200-kDa (NF-H) neurofilaments in pituitary thyrotrophs of rats, made hypothyroid by propylthiouracil (PTU) administration. Rats were sacrificed at 3, 7, 14, and 28 d of PTU administration as well as at 3, 7, and 14 d after interruption of a 14-d PTU treatment. The pituitaries were fixed, dehydrated, and embedded in paraffin. Consecutive sections were prepared for the immunohistochemical demonstration of thyroid-stimulating hormone and NF-H. NF-H were found in some thyrotrophs of the adenohypophysis of control rats. NF-H were expressed in thyroidectomy cells of hypothyroid rats. Discontinuation of PTU treatment led to recovery from cytologic alterations in the thyroidectomy cells expressing NF-H.
  Endocrine Pathology 04/2012; 11(2):195-200.
• Article: Immunohistochemical Analysis of 11-β-Hydroxysteroid Dehydrogenase Type 2 and Glucocorticoid Receptor in Subclinical Cushing’s Disease due to Pituitary Macroadenoma

  Takanori Ebisawa, Katsuyoshi Tojo, Naoko Tajima, Masami Kamio, Yutaka Oki, Katsuhiko Ono, Hironobu Sasano
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  ABSTRACT: Subclinical Cushing’s disease (SCD) is characterized by lack of clinically evident Cushingoid features, despite abnormal hypersecretion of ACTH. Nearly half the cases of SCD are due to macroadenomas, and in the majority of them, ACTH secretion is not inhibited even by high-dose dexamethasone. Impaired glucocorticoid (GC) action may be correlated with the proliferation and development of pituitary macroadenomas causing SCD. In this study, immunohistochemical analysis of the resected tumors were performed to evaluate the expression of 11β-hydroxysteroid dehydrogenase type 2 (11βHSD2) and glucocorticoid receptor (GR) in pituitary tissues obtained from two SCD (macroadenomas), eight Cushing’s disease (CD) (microadenomas), nine acromegaly, and nine normal pituitary (NP). Scattered 11βHSD2-immunopositive cells were detected in all NP tissues, but its immunoreactivity was totally absent in any tumorous tissues except two CD. Scattered GR-immunopositive cells were also detected and GR immunostaining was restricted to the cytosol in NP tissue. In contrast, GR-immunopositive cells were abundantly present and GR immunostaining was restricted to the nucleus in all the tumorous tissues. There were marked differences in both expression levels and localization between NP tissues and all the tumors. There may be a mechanism other than that via 11βHSD2 for causes of impaired negative feedback action by GC in SCD and CD, but results of our present study suggest that impaired GC action may be involved, at least in part, in tumorigenesis of SCD and CD.
  Endocrine Pathology 04/2012; 19(4):252-260.
• Article: Combined riedel’s disease and fibrosing hashimoto’s thyroiditis: A report of three cases with two showing coexisting papillary carcinoma

  Zubair W. Baloch, Michael D. Feldman, Virginia A. LiVolsi
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  ABSTRACT: Extensive sclerosis of the thyroid gland can be seen in both benign and malignant conditions. The benign sclerosing lesions of the thyroid include Riedel’s disease and fibrosing Hashimoto’s thyroiditis. Although these conditions usually occur separately, rarely can they occur simultaneously. In malignant lesions, papillary thyroid carcinoma and anaplastic carcinoma of the thyroid can be associated with extensive sclerosis leading to partial or total effacement of the tumor. We report on three cases that showed simultaneous occurrence of Riedel’s disease and fibrosing Hashimoto’s thyroiditis. Two of these cases also showed papillary carcinoma (one case of Warthin’-like papillary carcinoma and one case of classic type). All patients were females (age range 32–67 yr) and presented with elevated antithyroglobulin antibodies. Two patients presented with a solitary thyroid mass, and from these one had multiple bilateral neck nodes and a paravertebral mass. The third patient presented with a multinodular gland adherent to neck structures. All patients underwent total thyroidectomy. Histologic sections showed extensive replacement of the thyroid parenchyma with dense keloidal fibrosis, intermixed well-developed lymphoid follicles, and scattered lymphocytes and plasma cells. In all cases the fibrotic process extended beyond thyroid capsule with involvement of the perithyroidal soft tissues and skeletal muscle consistent with Riedel’s disease. One case showed a classic papillary carcinoma with bilateral lymph node metastases, and the other showed a Warthin’s-like papillary carcinoma. In both cases the papillary cancers were surrounded by dense sclerosis. Immunohistochemical stains for B- and T-markers and immunoglobulin light chains showed a polyclonal population of the lymphoid cells. The simultaneous occurrence of Riedel’s disease and fibrosing Hashimoto’s thyroiditis is rare and most likely represents a coincidental phenomenon, because both of these conditions are distinct clinicopathologic entities.
  Endocrine Pathology 04/2012; 11(2):157-163.