Atypical Carcinoid Tumor of the Lung, Associated with Giant-cell Transformation in Bone Metastasis

A case of neuroendocrine lung tumor located beneath the pleura in a 71 year old woman is reported. At autopsy, the tumor was found to have metastasized to the bones and liver without involving the hilar lymph nodes. Histological-ly, the tumor cells at the primary site and in the liver metastasis exhibited a carcinoid-like organoid structure, whereas pleomorphic giant cells were noted in the bone metastasis. The argyrophilic tumor cells were immuno-reactive for neuron specific enolase, chromogranin A, serotonin, calcitonin, calcitonin gene-related peptide, gas-trin-releasing peptide, neuropeptide Y, gastrin, pancreatic polypeptide, glicentin, the alpha subunit of human cho-rionic gonadotropin, keratin, epithelial membrane antigen, Leu M1 and carcinoembryonic antigen. Electron microscopy revealed abundant neurosecretory granules in the cytoplasm. This was considered to be a rare case of neuroendocrine lung tumor showing carcinoid like histology at the primary site and large-cell transformation in bone metastasis.     

Neuroendocrine carcinoma of the liver associated with dermatomyositis: autopsy case and review of the literature

Reported herein is an autopsy case of primary hepatic neuroendocrine carcinoma associated with dermatomyositis. A 71-year-old Japanese man, who was diagnosed with dermatomyositis 5 months before death, had multiple tumors within a non-cirrhotic liver. Histopathologically, the tumors were composed of small- and medium-sized round cells with clear cytoplasm arranged in nests, sheets or rosettes. Immunohistochemically, the tumor cells were positive for chromogranin A, neuron-specific enolase and CD56 and were negative for synaptophysin. This tumor was diagnosed as a primary hepatic neuroendocrine carcinoma with metastasis to the lung, gallbladder and lymph nodes around the pancreas and aorta; no primary lesions were detected in any other organ. The tumor cells were also positive for cytokeratin 7, cytokeratin 19 and epithelial membrane antigen but were negative for anti-hepatocyte antibody and AFP. These findings suggest that the tumor originated in intrahepatic bile duct epithelium. Various cancers have been reported in patients with dermatomyositis, but only seven cases of dermatomyositis associated with primary liver cancer have been reported. To the best of the authors' knowledge, this is the first report of dermatomyositis associated with primary hepatic neuroendocrine carcinoma.     

Rectal Carcinoid Tumor Metastasizing to the Thyroid and Pancreas: An Autopsy Case Exploiting Immunohistochemistry for Differentiation from Tumors Involving Multiple Endocrine Organs

A 58-year-old male patient with rectal carcinoid tumor is presented. The tumor extensively involved the lymph nodes and liver, and multiple tumors were also recognized in the pancreas and thyroid. Grossly, it was uncertain whether the latter were metastases from the rectal carcinoid or all were coincident primary tumors involving multiple endocrine organs, so-called multiple endocrine neoplasia (MEN) syndrome. Histologic, histochemical and electron microscopic examinations of the tumors in both the pancreas and thyroid showed similar features to those of the rectal carcinoid. The neoplastic cells in all involved organs commonly expressed positive immunoreactivity for somatostatin, but negativity for carcinoembryonic antigen, calcitonin, calcitonin gene-related peptide, thyroglobulin, insulin, glucagon and pancreatic polypeptide. These immunohistochemicai results confirmed that the tumors observed in multiple endocrine organs were indeed metastatic from the rectal carcinoid, rather than being a new combination of MEN syndrome. Some neuroendocrine tumors may develop widespread metastasis, sometimes creating problems with differentiation from multiple primary endocrine tumors. lmmunohistochemistry may be of great help in setting this issue.     

Rectal carcinoid tumor metastasizing to the thyroid and pancreas. An autopsy case exploiting immunohistochemistry for differentiation from tumors involving multiple endocrine organs

A 58-year-old male patient with rectal carcinoid tumor is presented. The tumor extensively involved the lymph nodes and liver, and multiple tumors were also recognized in the pancreas and thyroid. Grossly, it was uncertain whether the latter were metastases from the rectal carcinoid or all were coincident primary tumors involving multiple endocrine organs, so-called multiple endocrine neoplasia (MEN) syndrome. Histologic, histochemical and electron microscopic examinations of the tumors in both the pancreas and thyroid showed similar features to those of the rectal carcinoid. The neoplastic cells in all involved organs commonly expressed positive immunoreactivity for somatostatin, but negativity for carcinoembryonic antigen, calcitonin, calcitonin gene-related peptide, thyroglobulin, insulin, glucagon and pancreatic polypeptide. These immunohistochemical results confirmed that the tumors observed in multiple endocrine organs were indeed metastatic from the rectal carcinoid, rather than being a new combination of MEN syndrome. Some neuroendocrine tumors may develop widespread metastasis, sometimes creating problems with differentiation from multiple primary endocrine tumors. Immunohistochemistry may be of great help in setting this issue.     

Tumor-to-tumor metastasis to follicular variant of papillary carcinoma of thyroid.

OBJECTIVE: To describe and document tumor-to-tumor metastases in the thyroid gland. METHODS AND RESULTS: In this series we describe 3 cases of tumor-to-tumor metastasis in which the recipient tumor was a follicular variant of papillary thyroid carcinoma. The donor tumors and sites were small cell carcinoma of the lung, neuroendocrine carcinoma probably of pancreatic origin with initial presentation as liver metastasis, and clear cell carcinoma of the kidney with metastasis to liver and pancreas. The donor tumor cells infiltrated the substance of the follicular variant of papillary thyroid carcinoma, the nontumorous thyroid parenchyma, and the lymphovascular spaces. Small cell carcinoma and neuroendocrine carcinoma showed positive reactivity for neuroendocrine markers and were negative for thyroglobulin and calcitonin. The follicular variant of papillary thyroid carcinoma showed positivity with thyroglobulin and cytokeratin 19. CONCLUSIONS: Although tumor-to-tumor metastases in thyroid gland are exceedingly rare, one should be aware of this phenomenon as the metastatic lesion may simulate a thyroid primary. History of a previous tumor and immunohistochemical stains can be helpful in distinguishing between primary and metastatic thyroid neoplasms.     

Rectal adenocarcinoid with lymph node metastasis

We describe a case of a rare variant of a rectal carcinoid tumor that showed mucous gland differentiation accompanied by a lymph node metastasis with a histological appearance similar to that of the primary site. The tumor consisted of a typical argyrophilic carcinoid component and of goblet cell glands. The carcinoid component was positive for neuron-specific enolase, chromogranin A and synaptophysin. The goblet cells stained positively with periodic acid-Schiff (PAS) and alcian blue, and expressed carcinoembryonic antigen, but were negative for neuroendocrine markers. This case suggests that carcinoid tumor can differentiate towards mucus glands, which can also be found in the metastatic site.     

Bone marrow infiltrate by a poorly differentiated neuroendocrine carcinoma

We report a rare case of bone marrow infiltrate by a neuroendocrine carcinoma. The patient was a 66-year-old man who presented with anemia and thrombocytopenia and with a leukoerythroblastic picture on blood films. A bone marrow biopsy revealed extensive tumor infiltrate with morphological and immunohistochemical features of neuroendocrine origin. There were also multiple nodular lesions in the liver, which showed the same pathology as that in the bone marrow. Since none of the lesions could be identified as the primary tumor, the patient was diagnosed to have a poorly differentiated neuroendocrine carcinoma of unknown primary site.     

Primary duodenal small-cell neuroendocrine carcinoma with production of vasoactive intestinal polypeptide

A primary duodenal small-cell neuroendocrine carcinoma was found in an elderly man who presented with upper abdominal pain. Although metastatic small-cell carcinoma was documented by liver biopsy, the primary lesion was not identified until postmortem examination. The latter tumor, which ulcerated the duodenal mucosa, was composed of small ovoid cells with sparse cytoplasm and granular chromatin. Electron microscopy revealed cytoplasmic dense-core granules. Immunocytochemical study demonstrated the presence of neuron-specific enolase, Leu 7 antigen, chromogranin, epithelial membrane antigen, and vasoactive intestinal polypeptide within tumor cells. However, there was no evidence of a clinical endocrinopathy. This case emphasizes the need to include the duodenum as a possible primary site when metastatic small-cell neuroendocrine carcinoma is seen in the absence of apparent pulmonary disease.     

Moderately differentiated neuroendocrine carcinoma (atypical carcinoid) of the supraglottic larynx. A report of two cases including immunohistochemistry and aspiration cytology.

Moderately differentiated neuroendocrine carcinoma of the larynx is morphologically distinct from the classic carcinoid and small-cell carcinoma. It is composed of medium to large polyhedral cells with an insular, trabecular, or acinar growth pattern, variable pleomorphism, and a tendency to metastasize to skin and bone. We describe the clinicopathological features of the tumor in two patients in whom tumor dissemination resulted in death 13 and 33 months after diagnosis. Both tumors occurred above the glottis and metastasized to bone but not to regional tissues. In one case, the diagnosis was confirmed when the aspiration cytological specimen from a rib lesion suggested a neuroendocrine carcinoma resembling medullary thyroid cancer (triangular cytoplasm, double nuclei, and fine red cytoplasmic granules on May-Grünwald-Giemsa staining). Both tumors were originally misdiagnosed as squamous cell carcinoma, as acinic cell cancer, or as suggesting metastasis of melanoma. Immunohistochemistry gave strong reactivity in both for chromogranin A and calcitonin, although the serum level of calcitonin, determined in one case, was normal.     

Neuroendocrine small cell carcinoma of the breast: report of a case

A rare case of neuroendocrine small cell carcinoma (SmCC) of the breast is reported. A 51-year-old postmenopausal woman noticed a nodule approximately 3 cm in diameter in her right upper breast. Histologically, the tumor consisted of small ovoid to pleomorphic cells with hyperchromatic nuclei, and a large central area was occupied by acellular amorphous tissue. Extensive lymphatic permeation was seen around the tumor. Invasive and in situ ductal carcinoma foci were not observed in and surrounding the tumor. Immunohistochemically, estrogen and progesterone receptors and HER2/neu were all negative in the tumor cells. Synaptophysin and chromogranin A were diffusely positive in the tumor cells. Cytokeratin 8 was only positive in a few tumor cells. The labeling indices of Ki-67 and p53 were high in the tumor. Postoperatively, systemic studies including positron emission tomography were performed but failed to reveal any other possible primary sites, including lung. Based on these findings, the tumor was diagnosed as neuroendocrine primary SmCC of the breast. Postoperatively, the patient received a course of weekly paclitaxel. However, pelvic bone metastasis was identified on a bone scintigram 1 year after surgery. Mammary SmCC showing high Ki-67 and p53 index should be treated carefully because of their aggressive clinical behavior.     

C cell carcinoma of the thyroid. Follicular variant

A case of C cell carcinoma of the thyroid with an unusual follicular growth pattern of the cancerous C cells is described. The primary tumor consisted of a mixture of medullary and follicular features while the metastatic foci in the lymph nodes and liver displayed only a medullary arrangement. Histochemical study disclosed numerous argyrophilic cells in both the follicular and medullary parts. These cells were immunohistochemically positive for calcitonin, calcitonin gene-related peptide (CGRP) and other peptides as well as carcinoembryonic antigen (CEA), but negative for thyroglobulin. Radioimmunoassay done on the tissue extract revealed a high content of calcitonin. Electron microscopy showed small intracytoplasmic secretory granules and, in the follicular lining cells, formation of microvilli. A minor component consisting of glandular structures has been reported in medullary carcinoma of the thyroid, suggesting a potentiality for glandular differentiation of the C cells. In equivocal cases, immunohistochemical examination for calcitonin and thyroglobulin is essential for accurate diagnosis of thyroid carcinoma.     

C Cell Carcinoma of the Thyroid Follicular variant

A case of C cell carcinoma of the thyroid with an unusual follicular growth pattern of the cancerous C cells is described. The primary tumor consisted of a mixture of medullary and follicular features while the metastatic foci in the lymph nodes and liver displayed only a medullary arrangement. Histochemical study disclosed numerous argyrophilic cells in both the follicular and medullary parts. These cells were immunohistochemically positive for calcitonin, calcitonin gene-related peptide (CGRP) and other peptides as well as carcinoembryonic antigen (CEA), but negative for thyroglobulin. Radioimmunoassay done on the tissue extract revealed a high content of calcitonin. Electron microscopy showed small intracytoplasmic secretory granules and, in the follicular lining cells, formation of microvilli. A minor component consisting of glandular structures has been reported in medullary carcinoma of the thyroid, suggesting a potentiality for glandular differentiation of the C cells. In equivocal cases, immuno-histochemical examination for calcitonin and thyroglobulin is essential for accurate diagnosis of thyroid carcinoma. Acta Pathol Jpn 39: 393-399, 1989.     

Metastatic medullary thyroid carcinoma or calcitonin‐secreting carcinoid tumor of lung? A diagnostic dilemma in a patient with lung mass and thyroid nodule

Calcitonin‐secreting neuroendocrine tumors are rare and have been reported in literature as case reports or case series in various organs including lung, pancreas, larynx, bladder, and ovary. These tumors have similar cytologic features and immunohistochemical profile to medullary thyroid carcinoma and thus it is difficult to distinguish them, especially when calcitonin‐secreting neuroendocrine tumors are intermediate or higher grade and there is a mass lesion in the thyroid gland. Here, we report a rare case of calcitonin secreting atypical carcinoid tumor of the lung in a patient with thyroid nodule. However, after extensive ancillary studies on the thyroid gland, no tumor was detected and subsequent resection specimen revealed a pulmonary atypical carcinoid tumor with metastasis to level 11 lymph node. Being aware of this entity has significant clinical, diagnostic, and therapeutic implications and can prevent unnecessary thyroidectomies with subsequent possible morbidities.     

Medullary thyroid carcinoma with poor differentiation and atypical radiographic pattern of metastasis

A diagnosis of sporadic medullary thyroid carcinoma (MTC) is complicated. On first diagnosis it may present with distant metastasis. There has been inconsistency regarding metastatic MTC tissue expression of calcitonin, its tumor marker. Adding to the difficulty is the fact that the radiographic pattern of pulmonary metastasis from MTC may vary substantially among patients. Herein is reported the case of a 73-year-old man who presented with two ill-defined pulmonary opacities, clinically resembling primary lung carcinoma. MTC was diagnosed on histopathology of tissue obtained from a total thyroidectomy. The pulmonary biopsy specimens were confirmed to be MTC metastasis on positive immunohistochemical staining of chromogranin-A and synaptophysin, even though only a few cells were stained for calcitonin. To the authors' knowledge this is the first reported case of MTC presenting initially as complex pulmonary metastasis with weakened expression of calcitonin in the metastatic lesion.     

Von Recklinghausen's Disease Associated with Somatostatin-rich Duodenal Carcinoid (Somatostatinoma), Medullary Thyroid Carcinoma and Diffuse Adrenal Medullary Hyperplasia

This report describes the concomitant occurrence of a somatostatin-rich duodenal carcinoid, a medullary thyroid carcinoma and a diffuse adrenal medullary hyperplasia in a patient with von Recklinghausen's disease. A 50-year-old Japanese man died from lung metastasis of a malignant schwannoma. In addition to extensive viscero-cutaneous neurofibromatosis, two different types of neuroendocrine tumors were found in the duodenum and thyroid gland at autopsy. The duodenal tumor, which was located in the second portion, showed the histologic appearance of a carcinoid tumor with glandular differentiation and psammoma-bodies. Immunohistochemically the tumor cells were intensely positive for somatostatin. The thyroid tumor was composed of nests of tumor cells arranged in an endocrine pattern, and showed immunoreactivity for calcitonin. A review of the literature revealed no previously reported case of concomitant occurrence of duodenal somatostatinoma and medullary thyroid carcinoma in a single patient with von Recklinghausen's disease. Morphometric analysis of adrenal glands disclosed the presence of diffuse medullary hyperplasia. Thus, the present case exhibited a similarity in some respects with multiple endocrine neoplasia (MEN) syndrome, Type Ila or IIb.     

von Recklinghausen's disease associated with somatostatin-rich duodenal carcinoid (somatostatinoma), medullary thyroid carcinoma and diffuse adrenal medullary hyperplasia.

This report describes the concomitant occurrence of a somatostatin-rich duodenal carcinoid, a medullary thyroid carcinoma and a diffuse adrenal medullary hyperplasia in a patient with von Recklinghausen's disease. A 50-year-old Japanese man died from lung metastasis of a malignant schwannoma. In addition to extensive viscero-cutaneous neurofibromatosis, two different types of neuroendocrine tumors were found in the duodenum and thyroid gland at autopsy. The duodenal tumor, which was located in the second portion, showed the histologic appearance of a carcinoid tumor with glandular differentiation and psammoma-bodies. Immunohistochemically the tumor cells were intensely positive for somatostatin. The thyroid tumor was composed of nests of tumor cells arranged in an endocrine pattern, and showed immunoreactivity for calcitonin. A review of the literature revealed no previously reported case of concomitant occurrence of duodenal somatostatinoma and medullary thyroid carcinoma in a single patient with von Recklinghausen's disease. Morphometric analysis of adrenal glands disclosed the presence of diffuse medullary hyperplasia. Thus, the present case exhibited a similarity in some respects with multiple endocrine neoplasia (MEN) syndrome, Type IIa or IIb.     

The morphologic spectrum of metastatic prostatic adenocarcinoma to the lung: special emphasis on histologic features overlapping with other pulmonary neoplasms

We undertook a detailed histologic study to identify specific morphologic features that may aid in distinguishing prostatic adenocarcinoma with lung metastases (PALM) from other pulmonary tumors with similar histologic features. In 16 cases, we found 3 predominant architectural patterns: microacinar (n = 10), tubulopapillary (ductal; n = 4), and carcinoid-like (n = 2). Characteristic features of PALM included small acinar and/or cribriform growth, frequent lymphangitic permeation, lack of stromal response, uniform round nuclei with prominent nucleoli, intraluminal blue mucin, and prominent cell borders. By immunohistochemical staining, prostate-specific antigen and prostate-specific acid phosphatase were present in 13 of 14 and 13 of 13 cases, respectively. Metastatic prostatic duct adenocarcinoma exhibited morphologic features similar to metastatic colonic adenocarcinoma. Two cases had a carcinoid-like appearance with nested or solid architecture, parachromatin clearing, and prominent nucleoli, but lacked the finely stippled chromatin pattern of carcinoid tumors. Several features that may result in misinterpretation or lack of association of the neoplasm in the lung with a prostatic primary include lung metastasis preceding the detection of a prostatic primary tumor, solitary pulmonary nodule, tubulopapillary (ductal) or carcinoid-like pattern, scant material in which histologic features of metastatic prostate carcinoma are not fully appreciated, and frequent necrosis. Attention to specific discriminating histologic features, supported by immunohistochemical staining, may be useful in the differential diagnosis, which is therapeutically and prognostically critical.     

Neuroendocrine carcinoma of the liver: An autopsy case

An autopsy case of hepatic neuroendocrine carcinoma Is descrlbed. An 84-year-old man had a white solid tumor measuring 5 cm In greatest diameter and multiple small nodules In the non-cirrhotic liver. Microscopically, these lesions were characterized by solid nesting, trabecular, and Insular arrangements of small- to medium-sized cells. The tumor cells were argyrophllic and electron microscopy showed dense core granules and formation of bile canall-culi. lrnmunohlstochernlcally, the tumor cells were positive for cytokeratln CAM 5.2, chromogranln A, Leu-7, neuron-specific enolase, and α-fetoprotein. The tumor was diploid by flow cytometry. The patient had metastases in the vertebrae, lung, pancreas, and an hepatic hilar lymph node. The patient had an occult rectal tumor of Intramucosal well-differentiated tubular adenocarcinoma without metastasis. No alternative primary source of the endocrine tumor was detected. The patient died 1 month after presentation.     

Indolent neuroendocrine tumor involving the bone marrow. A case report with a 9-year follow-up

We report a unique case of a patient with a neuroendocrine tumor localized to the bone marrow. The patient had a history of hairy cell leukemia, and the neuroendocrine tumor was detected in a bone marrow biopsy specimen obtained to assess response to 2-chlorodeoxyadenosine therapy. The neuroendocrine tumor was present as nodules that replaced approximately 15% of the bone marrow medullary space and was composed of round cells with fine chromatin, indistinct nucleoli, and relatively abundant, granular, eosinophilic cytoplasm. Histochemical stains showed cytoplasmic reactivity with Grimelius and Fontana-Masson stains, and immunohistochemical studies showed positivity for keratin and chromogranin. The histologic, cytochemical, and immunohistochemical features resembled a carcinoid tumor, and metastasis to the bone marrow was considered initially. The patient was asymptomatic without diarrhea, flushing, or cardiac valve disease. Serotonin production, assessed by the measurement of serum 5-hydroxyindoleacetic acid and substance P levels, was normal. Extensive clinical and radiologic work-up and endoscopy of the gastrointestinal tract to detect a primary site other than the bone marrow were negative. Follow-up bone marrow biopsy 7 years after the initial diagnosis was positive for persistent neuroendocrine tumor. The patient has not received any therapy specific for the neuroendocrine tumor and has had no clinical symptoms or evidence of progression after 9 years of clinical follow-up. We suggest that this neuroendocrine tumor may have arisen in the bone marrow.