Oxyphil and squamous variants of medullary thyroid carcinoma

Two unusual morphologic variants of medullary thyroid carcinoma not previously described are reported. The first tumor was composed predominantly of large eosinophilic cells indistinguishable at the light microscopic level from Hürthle cells. Focal areas of conventional medullary carcinoma were also present. Electron microscopic study showed mitochondrion-rich cells containing round neurosecretory granules. Immunoreactive calcitonin and carcinoembryonic antigen (CEA) were demonstrated within most tumor cells. The second tumor had areas of typical medullary carcinoma but exhibited extensive squamous differentiation. The tumor was positive for CEA, neuron-specific enolase, and chromogranin but negative for calcitonin. Oxyphil and squamous cells must be added to the long list of cell types that have been described in medullary thyroid carcinoma.     

Calcitonin as a tumor marker for nonthyroid neoplasia

Plasma levels of calcitonin have been utilized as a tumor marker for medullary carcinoma of the thyroid. Elevated calcitonin levels have been noted with other tumors as well. The present case documents a marked decrease in calcitonin levels following therapy for breast carcinoma, supporting further evaluation of calcitonin as a clinically useful tumor marker for nonthyroid neoplasm.     

Mixed Medullary-follicular Thyroid Carcinoma： Report of a Case and Review of the Literarture

Mixed medullary-follicular carcinomas （MMFCs） are tumors of the thyroid that display morphological and immunohistochemical features of both medullary and follicular neoplasms. These tumors are rare and less than 40 cases have been described in the literature since the early 1980s The term medullary-follicular thyroid carcinoma denotes a tumor which exhibits the features of a medullary carcinoma and shows positive expression of calcitonin on immunohistochemistry. It is a follicular-derived thyroid carcinoma and is positive for thyroglobulin expression within the same tumor. Most reported cases have lymph node involvement at the time of diagnosis. In cases having disease progression, distant metastases develop in the lung, liver, mediastinum and bone. We report a case of a male patient with mixed medullary-follicular thyroid carcinoma and a review of the literature.     

Coexistence of MEN 2A and Papillary Thyroid Carcinoma and a Recurrent Pheochromocytoma 23 Years after Surgery: Report of a Case and a Review of the Japanese Literature

A 59-year-old woman who had undergone bilateral partial adrenalectomy23 years previously was referred to our hospital because ofneck masses and a left adrenal tumor. Fine needle aspirationbiopsy of the neck tumor and elevated levels of calcitonin andCEA revealed medullary thyroid carcinoma. Slightly elevatedlevels of urinary normetanephrine and metanephrine, and resultsof a clonidine suppression test, CT, magnetic resonance imaging,and ¹³¹l-metaiodo-benzylguanidine scintigraphy of the abdomenindicated that the left adrenal tumor was a recurrent pheochromocytomain the residual adrenal gland. After total thyroidectomy, bilateralmedullary thyroid carcinomas and papillary thyroid carcinomawere recognized pathologically. Although the coexistence ofbilateral pheochromocytoma and medullary thyroid carcinoma issuggestive of multiple endocrine neoplasia (MEN), associationof MEN type 2A (MEN 2A) with papillary thyroid carcinoma mayhave occurred incidentally. A retrospective analysis of 9 casesof pheochromocytoma associated with papillary thyroid carcinomareported in the Japanese literature demonstrated a male-to-femaleratio of 1:8, and an average patient age of 56.2 years. Thepresent case indicates that association between pheochromocytomaand thyroid carcinoma may not always involve medullary thyroidcarcinoma.     

联合检测 CT、CEA 对术中诊断甲状腺髓样癌的意义

目的：探讨术前、术中诊断甲状腺髓样癌的方法,以提高甲状腺髓样癌的诊断准确率。方法：采用酶联免疫吸附试验和化学发光法分别于术前对甲状腺结节病人进行血清降钙素（CT）、癌胚抗原（CEA）检测。对 CT、CEA 水平升高患者,术中观察冰冻切片的同时用冰冻切片进行 CT、CEA、CK19、TTF －1、CD56、Syn、Cga免疫组化染色。对比分析血清中 CT、CEA 水平与甲状腺髓样癌组织中 CT、CEA 的关系及术中、术后 CT、CEA、CK19、TTF －1、CD56、Syn、Cga 免疫组化结果。结果：2007年1月至2013年8月间共诊断甲状腺髓样癌32例,术前血清 CT 或 CEA 水平升高患者中经过病理切片观察和免疫组化染色共检出髓样癌22例（22／40,55．00％）,明显高于血清 CT 水平和血清 CEA 水平正常组检出的10例（10／655,1．53％）（P ＜0．05）,血清 CT和 CEA 水平在甲状腺髓样癌中呈正相关（P ＜0．05）;血清 CT、CEA 水平与甲状腺髓样癌组织中 CT、CEA 表达一致（均 P ＜0．05）。术中病理免疫组化结果与术后免疫组化对比,未见假阴性。结论：对术前血清 CT、CEA水平升高的甲状腺结节患者,术中结合 CT、CEA、CK19、TTF －1、CD56、Syn、Cga 免疫组化染色,能够明显提高术中甲状腺髓样癌诊断准确率。此法具有准确率高、快速、简便、经济等优势,解决术前或术中甲状腺髓样癌诊断困难、误诊、漏诊率高的问题,适合推广。     

Simultaneous occurrence of medullary carcinoma and papillary carcinoma and papillary carcinoma of the thyroid

We report a case of simultaneous occurrence of medullary carcinoma and papillary carcinoma of the thyroid in the same thyroid gland. Immunoreactivity of calcitonin, carcinoembryonic antigen, neuron specific enolase and thyroglobulin made a sharp distinction between both neoplasms of the thyroid. It appears reasonable to consider that simultaneous occurrence of medullary carcinoma and papillary carcinoma of the thyroid in this case does not have embryological or genetical significance. © 1995 Wiley-Liss, Inc.     

Hepatocellular carcinoma metastasis in the pituitary gland: case report and review of the literature

Symptomatic pituitary metastases are uncommon and have been reported mainly in autopsy series. Although all types of malignancies can metastasize to the pituitary gland, a review of the literature has indicated that lung and breast carcinomas are the most frequent primary tumors while hepatocellular carcinoma metastasis has only recently been described.A 59-year-old man with abdominal pain and fever was admitted to our hospital. Hepatosplenomegaly was present without signs of ascites. Laboratory tests showed only abnormal hepatic biochemistry while the radiological studies revealed a solid mass occupying the left hepatic lobe. The patient underwent excision of the left hepatic lobe and was closely followed-up. Six months later he readmitted with headache and visual disturbances. MRI revealed a solid mass in the sella region pressing the optic chiasma. Transsphenoidal excision of the pituitary mass was followed and the histological examination of the tumor was compatible with hepatocellular carcinoma.Symptomatic pituitary metastases are uncommon and may be difficult to differentiate from pituitary adenomas. The present case emphasizes on the capricious nature of hepatocellular carcinoma and on the importance of the individualized therapeutic approach.     

Pathological changes after radiotherapy for primary pituitary carcinoma: a case report

Pituitary carcinomas are extremely rare. The definition, diagnosis, therapy, and prognosis are controversial. So far, to our knowledge, there has been no report regarding pathological changes after radiotherapy for primary pituitary carcinoma. We reported a single case of a presumed prolactin staining pituitary carcinoma. We defined carcinoma by premorbid intracranial dissemination of the tumor. There were no proven extracranial metastases. The tumor was silent on PET scanning. The patient received external beam radiotherapy alone as primary therapy. Post-irradiation histology revealed that necrotic tissue made up approximately more than half. Tumor had viable cells. Probably approximately three-fifth of tumor cells were without alteration and approximately two-fifth were with degeneration. We confirmed that necrosis but no apoptosis were coexistent in the cells post irradiation for pituitary carcinoma.     

Chromogranin A and the alpha-subunit of glycoprotein hormones in medullary thyroid carcinoma and phaeochromocytoma

Using specific immunoradiometric assays, we evaluated the clinical usefulness of chromogranin A and the alpha-subunit of glycoprotein hormones in neuroendocrine tumours of neuroectodermic origin. The serum alpha-subunit of glycoprotein hormones was only slightly increased in 2 out of 44 medullary thyroid carcinoma or phaeochromocytoma patients with increased calcitonin or 24-hour urinary metanephrine levels. Serum chromogranin A was increased in 12 of 45 (27%) medullary thyroid carcinoma patients with an elevated calcitonin level and in 4 of 16 medullary thyroid carcinoma patients (25%) with an undetectable calcitonin level, in 5 of 7 phaeochromocytoma patients with increased urinary catecholamine and metabolite excretion, and in 2 of 3 patients with a non-functioning phaeochromocytoma. During follow-up, the course of chromogranin A was found to parallel that of tumour burden and/or 24-hour urinary metanephrine in 5 phaeochromocytoma patients. We conclude that chromogranin A measurement is not recommended for the diagnosis of medullary thyroid carcinoma patients. It may be useful in patients with functioning and non-functioning phaeochromocytomas as a follow-up marker. In neuroendocrine tumour patients with elevated calcitonin secretion, the serum alpha-subunit of glycoprotein hormone measurement may help differentiate medullary thyroid carcinoma or phaeochromocytoma patients from other endodermal-derived neuroendocrine tumour patients in whom it is frequently elevated.     

Thyroid carcinoma

Among thyroid carcinomas, thyroglobulin is a good tumor marker for differentiated carcinoma (papillary carcinoma, follicular carcinoma). In particular, it is widely used for monitoring of patients with total or near-total thyroidectomy. On the other hand, medullary thyroid caricima has a very sensitive and specific tumor marker, calcitonin. In inherited medullary carcinoma (multiple endocrine neoplasia type 2), RET protooncogene analysis is the best for detecting early medullary thyroid carcinoma.     

The RET Mutation E768D Confers a Late-onset Familial Medullary Thyroid Carcinoma – Only Phenotype with Incomplete Penetrance: Implications for Screening and Management of Carrier Status

Objective: We describe a 4-generation family with familial medullary thyroid carcinoma (FMTC) – a variant of multiple endocrine neoplasia type 2 (MEN 2) without extra-thyroid features. RET mutation analysis confirmed an E768D mutation in exon 13 in 8 family members, 3 affected with medullary thyroid cancer alone while the other 5 were detected to be mutation carriers. This mutation has been described in very few families worldwide and the spectrum of disease and natural history is unclear. Results: Three affected members had medullary thyroid cancer (MTC) confirmed histologically at ages 25, 50 and 56 years, respectively. The E768D mutation appears to have a less aggressive clinical course compared to other high risk RET mutations with no evidence of clinical recurrence up to 11 years after initial therapy. Of five gene carriers identified, two are asymptomatic at the age of 70 and 61, and three had raised calcitonin levels at 46, 39, and 45 years. Following total thyroidectomy, one gene carrier had a histologically normal thyroid at age 46, following a mildly elevated calcitonin, one had C-cell hyperplasia at the age of 39, and one had a frank focus of carcinoma in the left thyroid lobe at the age of 45. No members had evidence of phaeochromocytoma or parathyroid disease on screening. Conclusion: The RET E768D mutation is associated with MTC with a later age at presentation, incomplete penetrance and less aggressive course compared with other high risk RET mutations. To date in this family the E768D mutation has not been associated with either phaeochromocytoma or hyperparathyroidism. The appropriate screening strategy for and management of E768D carriers is difficult reflecting the phenotypic heterogeneity.     

Early spontaneous deficiency of calcitonin renal binding sites in rats with a high incidence of calcitonin-secreting tumors (WAG/Rij)

Old rats of the WAG/Rij strain have a high incidence (50%) of medullary thyroid carcinoma, a calcitonin (CT)-secreting tumor. We have characterized and quantified the topographical distribution of [125I]salmon calcitonin (sCT) binding sites in the kidneys of this strain, as compared to Wistar CF rats (2% incidence of spontaneous medullary thyroid carcinoma). We report here that, up to 15 days of postnatal development, the distribution of CT-binding sites in the kidney of the WAG/Rij strain was quite similar to that found in developing and adult Wistar CF rats. However, from the age of 1 month, sCT-binding sites were dramatically reduced in both the medulla and the inner part of the kidney cortex, though plasma CT levels were not significantly different in both strains. Adult WAG/Rij rats bearing a transplanted tumor for 12 weeks had a high level of plasma calcitonin and exhibited an even greater reduction of both medullary and cortical sCT-binding sites. These results suggest that the modification in the CT-binding sites in WAG/Rij rats is not a consequence of a possible down regulation due to elevated circulating hormonal level but could be inherited and possibly associated with the later development of the tumor in this strain.     

Neuroendocrine tumor metastasis to the thyroid gland

It has been reported that the thyroid is relatively immune to malignant metastasis. Therefore, in a practical setting, it is difficult to diagnose whether synchronous nodules in both lung and thyroid are independent or have metastasized from one to the other. In the present study, we report a treatment approach in a patient with such nodules, using a molecular technique. A 68-year-old woman presented with synchronous solitary thyroid mass and a nodular lesion in the right lung. Both tumors, which were surgically resected, morphologically showed neuroendocrine differentiation, which was confirmed by immunohistochemical analysis. These features required differential diagnosis from possible (1) medullary thyroid carcinoma (MTC) with metastasis to the lung, (2) pulmonary neuroendocrine carcinoma with metastasis to the thyroid, and (3) independent MTC and pulmonary neuroendocrine carcinoma. Identical mutations of the p53 gene were detected in both the thyroid and lung tumors, indicating the same origin for both tumors. In addition, these mutations and a lack of calcitonin expression suggested a pulmonary origin of the tumors. Metastatic thyroid cancers are well known to cause miliary lesions in the lung, while lung cancers can metastasize to various tissues. Furthermore, pulmonary neuroendocrine carcinoma has been reported as having a tendency of metastasizing to the thyroid. Head and neck surgeons should be aware that a particular subset of lung cancers may develop a metastatic solitary nodule in the thyroid, as presented. An effective therapeutic strategy is largely dependent on the differential diagnosis.     

甲状腺髓样癌的神经内分泌激素免疫组化研究

目的 :探讨神经内分泌激素在甲状腺髓样癌表达的意义及在病理诊断和鉴别诊断中的应用价值。方法 :选择甲状腺髓样癌 10例 ,滤泡性腺癌、乳头状腺癌和未分化癌各 3例 ,行免疫组化LSAB法检测。结果 :10例髓样癌降钙素均阳性 ,嗜铬粒素A 8例 ,NSE 7例 ,Syn 4例 ,Somat 3例阳性 ;其他类型癌均呈阴性。结论 :降钙素是甲状腺髓样癌特异的标记物 ,其余内分泌激素的检出也有助于甲状腺髓样癌的诊断和鉴别诊断。     

Diagnostic approach, genetic screening and prognostic factors of medullary thyroid carcinoma

Medullary thyroid carcinoma is the least frequent thyroid neoplasm; it originates in thyroid parafollicular cells (calcitonin secreting C cells). In 80% of cases it is sporadic, in the remaining 20% it is familial, associated or not to other endocrinopathies as pheochromocytoma and hyperparathyroidism (MEN 2A, MEN 2B, and isolated familial medullary thyroid carcinoma). Preclinical diagnosis in relatives of affected subjects (preferably at pediatric age) is essential for successful therapy and is performed with genetic and biochemical screening tests. The genetic screening is based on DNA analysis (RET proto-oncogene mutations) of the patient, and if positive of all first degree relatives, to separate sporadic (somatic mutations) from familial (germline mutations) forms. The biochemical screening is based on calcitonin determination and its increase after pentagastrin stimulation, (a peculiar characteristic of medullary thyroid carcinoma, the first biochemical disorder in a subject at risk) and is mainly used in genetically silent familial medullary thyroid carcinoma. The principal negative prognostic factors of medullar thyroid carcinoma and the debate concerning the use of calcitonin determination in the diagnosis of the "cold" thyroid nodule have been analyzed.     

Histamine and calcitonin release from medullary thyroid carcinoma

The secretagogue effect of histamine on calcitonin secretion has been studied in 15 patients with medullary thyroid carcinoma and compared with known stimuli: glucagon and calcium in combination with pentagastrin. The effect of concomitant histamine H2-receptor blockade on these responses has been studied in the same patients. Seven patients with undetectable basal plasma calcitonin concentrations had measurable responses to calcium/pentagastrin but not to histamine or glucagon. In the remaining eight subjects, significant responses were seen to all three test substances, calcium/pentagastrin proving to be the most potent secretagogue. Establishment of H2-receptor blockade with cimetidine had no effect on basal calcitonin concentrations and did not suppress responses to histamine, calcium or pentagastrin. The variable secretagogue effect of histamine could be mediated through H1-receptors, through nonspecific vascular dilation "washing out" preformed calcitonin, or through its destruction to varying degrees by histaminase, present in most medullary thyroid tumors. Histamine is unlikely to replace calcium/pentagastrin as the most discriminative, provocative diagnostic agent in medullary thyroid carcinoma, but correlation of secretory responses with tissue histaminase concentrations and attempted blockade with differing antihistamines will further our understanding of this tumor.     

Strumal carcinoid of the ovary: an analysis of its components.

A strumal carcinoid of the ovary was studied by light and electron microscopy. Thyroglobulin was demonstrated within the strumal element by immunofluorescence, thus establishing the identity of the thyroid tissue. The carcinoid fulfilled the light and electron microscopic criteria for a mixed insular and trabecular example of this tumor. Intermediate zones between the two tissue elements showed mixed characteristics. No amyloid was found. Immunoreactive calcitonin was demonstrated in the tumor, suggesting the presence of C-cells or medullary carcinoma of the thyroid.     

Value of immunohistochemistry in the study of medullary cancer of the thyroid. Implications of the results for the concept of the APUD system and of apudomas

Immunohistochemical studies in medullary thyroid carcinoma demonstrate the presence of C cells secreting calcitonin but also of other cells secreting other peptides or proteins. These different cells exist in the tumor as well as in metastases. These results and other reported in the literature suggest a common ultimobranchial and endodermal origin for these cells.     

Tumor markers for endocrine neoplasms

Tumor markers for thyroid neoplasms include thyroglobulin, calcitonin, and CEA. Thyroglobulin is particularly useful in discriminating follicular carcinoma from its benign counterparts. The measurement may also be helpful in the postoperative follow-up of patients with either follicular carcinoma or papillary carcinoma. Measuring plasma calcitonin and CEA is essential in the diagnosis and postoperative management of patients with medullary carcinoma. Highly specific genetic tests may become an alternative strategy in cases of familial medullary carcinoma. No specific tumor markers are available for parathyroid carcinoma; however, clinical characteristics provide diagnostic clues.     

垂体转移癌

患者男性,51岁,因右侧肾透明细胞癌行右肾摘除术后21个月、右肾上腺转移性癌行腹腔镜肿瘤摘除术后8个月,出现头痛、多饮多尿、畏寒、纳差、双眼视力减退3个月,头颅MRI检查发现鞍区肿瘤而人院。经多学科讨论,认为该鞍区肿瘤以垂体瘤并卒中可能性大,但不排除垂体转移癌,需手术治疗,垂体转移癌临床极为罕见。经常规术前准备后行经右眉锁孔人路、鞍区肿瘤摘除术,术中肿瘤完全切除,术后病理证实为肾透明细胞癌垂体转移。