Cytology of metastatic neuroendocrine (Merkel-cell) carcinoma in pleural fluid. A case report

A case of Merkel-cell (neuroendocrine) carcinoma of the skin with extensive metastases, including pleural effusion, occurring over 20 years after primary resection and treatment, is reported. The histologic appearance of the primary neoplasm was identical to that seen in the biopsy specimens of the metastatic carcinoma involving the great toe and inguinal lymph nodes and to that of the residual neoplasm tissue found at necropsy. Electron microscopic examination of a lymph node metastasis demonstrated cytoplasmic microfilaments and numerous dense-core, peripheral, neurosecretory granules, as previously described in Merkel-cell carcinoma. Cytologic examination of a pleural fluid specimen demonstrated numerous small malignant cells closely resembling the cells seen in the histopathologic sections from the surgical and necropsy tissues involved by metastatic carcinoma. This is the first report of the cytologic findings in a patient with Merkel-cell carcinoma metastatic to the pleural cavity.     

Immunohistochemical consistency between primary tumors and lymph node metastases of gastric neuroendocrine carcinoma

ABSTRACT: BACKGROUND: Gastric neuroendocrine carcinoma (G-NEC) is a rare, highly malignant tumor that exhibits aggressive growth leading to vascular invasion, distant metastasis and extremely poor prognosis. We studied the clinicopathological findings of seven patients at our institute to better under this disease. METHODS: Seven cases of G-NEC were identified among 1,027 cases of gastric carcinoma that underwent gastrectomy at Kansai Rousai Hospital between 2002 and 2010. We studied the pathological and immunohistochemical features of gastric neuroendocrine carcinomas at both the primary site and metastatic lymph nodes. RESULTS: The mean patient age was 73 years (range 63 to 86 years). There were no females in this series. The final staging was Stage I in one case, Stage II in two, Stage III in two and Stage IV in two. A total of 31 metastatic lymph nodes were found in these patients. This study revealed that the ratio of neuroendocrine cells was similar between the primary and metastatic sites, which tended to show the same expression patterns of neuroendocrine markers. CONCLUSIONS: Metastatic lymph nodes showed heterogeneous immunohistochemical expression patterns similar to the primary sites. G-NEC is far advanced at diagnosis and rapidly reaches the lymph nodes retaining its heterogeneity, carrying a worse prognosis than common gastric cancer.     

Lifestyle and clinical factors associated with elevated C-reactive protein among newly diagnosed Type 2 diabetes mellitus patients: a cross-sectional study from the nationwide DD2 cohort

The involvement of the testis by metastatic medullary thyroid carcinoma has never been described before. We describe the first case of metastatic medullary thyroid carcinoma affecting testis and inguinal lymph nodes. A 73-year-old Caucasian man was referred to undergo urologic surgery due to a painless nodule in the right testis and an homolateral inguinal lymphoadenomegaly. The patient had a history of medullary thyroid carcinoma with relapsing disease to the spine and lung nodules. Serum calcitonin and CEA levels were 175 pg/ml and 22 ng/ml, respectively. With suspected testicular cancer, the patient underwent radical right orchiectomy with the excision biopsy of the right inguinal lymph node. Histopathology and immunohistochemistry revealed that both the lesions were due to metastases from medullary thyroid carcinoma. Metastases to the testis and inguinal lymph nodes may be due to various solid and hematological tumors. This case, despite its rarity, suggests that testis and inguinal lymph nodes should be considered as potential secondary sites of medullary thyroid carcinoma as well.     

Fine needle aspiration biopsy of neuroendocrine breast carcinoma metastatic to the thyroid. A case report

BACKGROUND: Tumors showing neuroendocrine differentiation arise in a wide range of organs, and metastatic neuroendocrine tumors may be difficult to differentiate from primary tumors. This report describes an unusual case of metastatic breast carcinoma with neuroendocrine differentiation that presented as a solitary thyroid nodule. The diagnosis was made by fine needle aspiration biopsy (FNAB). CASE: A 52-year-old woman presented with a thyroid nodule and bilateral enlarged supraclavicular fossa lymph nodes. FNAB revealed a neuroendocrine carcinoma. Further questioning revealed that the patient had had a breast carcinoma resected eight years previously. The diagnosis of metastatic neuroendocrine breast carcinoma was established by immunocytochemistry. The patient received antiestrogen therapy but subsequently developed skeletal metastases. CONCLUSION: Neuroendocrine carcinomas from various sites show similar cytologic features. In this case, a diagnosis of breast carcinoma metastatic to the thyroid was suggested by the clinical history and confirmed by FNAB with immunocytochemistry.     

Neuroendocrine carcinoma of the pancreas diagnosed by aspiration cytology. A case report

Cytologic criteria for distinguishing endocrine from exocrine carcinomas of the pancreas have not been previously elucidated. A case is presented in which the diagnosis of neuroendocrine carcinoma was made on fine needle aspirates of a pancreatic mass and hepatic metastases in a 33-year-old female. Cytologically, the aspirated tumor resembled an intermediate-cell neuroendocrine carcinoma of the lung rather than the usual duct-cell adenocarcinoma of the pancreas. Histologic sections of the subsequently resected primary pancreatic mass revealed a neuroendocrine carcinoma of an intermediate-cell type. Ultrastructurally, the characteristic interlacing cytoplasmic processes with scanty granules were seen. Immunoreactive neuron-specific enolase (NSE), leuenkephalin, substance P and somatostatin were present in the tumor cells in Bouin's-fixed cell blocks of the aspirate; neuron-specific enolase, somatostatin and gastrin were detected in the paraffin-embedded sections of the resected tumor. This variant of pancreatic carcinoma merits recognition as a cytologically distinct group, which shares many of the features described in its bronchopulmonary and gastrointestinal counterparts.     

Paranuclear blue inclusions of small cell carcinoma of the stomach: report of a case with cytologic presentation in peritoneal washings

BACKGROUND: Primary gastric small cell carcinoma is a rare but important entity. We describe a case that we diagnosed by peritoneal washing cytology. CASE: A 70-year-old male presented with upper abdominal discomfort and underwent endoscopic evaluation. Gastric endoscopy revealed a diffuse, infiltrating tumor from the body to the antrum. Total gastrectomy with lymph node dissection and intraoperative peritoneal washing cytology were carried out. Peritoneal washing cytology showed the presence of many undifferentiated malignant small cells with a necrotic background. The tumor cells were small and round, with naked, hyperchromatic nuclei and finely granular chromatin. Some tumor cells contained paranuclear blue inclusions (PBls) in the cytoplasm. The tumor cells were positive for neuron-specific enolase and synaptophysin on immunocyto-chemistry. Carcinoembryonic antigen, alpha-fetoprotein (AFP) and leukocyte common antigen were negative. Pathologic diagnosis after the operation was moderately to poorly differentiated adenocarcinoma and small cell carcinoma containing AFP-positive cells. CONCLUSION: The prognosis of primary gastric small cell carcinoma is usually poor. Our patient died of multiple liver metastases and peritonitis carcinomatosa 69 days after surgery. When a gastric small cell carcinoma is suspected in peritoneal washings, immunocytochemical demonstration of neuroendocrine differentiation is required to arrive at the final diagnosis.     

Fine needle aspiration cytology of intranodal myofibroblastoma. A case report

BACKGROUND: Intranodal myofibroblastoma is a rare, primitive, mesenchymal neoplasm of the lymph nodes first described in 1989. It behaves in a benign fashion and has a great predilection for the inguinal region. CASE REPORT: A 56-year-old man was referred for fine needle aspiration cytology of an inguinal lymph node. Smears were moderately cellular, with a predominant population of single, small spindle cells with no atypia. Most neoplastic cells were distributed as dissociated, single cells, with few groups. The cells showed metachromatic stromal material with a fibrillary quality. Nuclei were elongated, with pointed ends and occasional twisted forms. A remarkable finding on Papanicolaou-stained smears was hemosiderin granules. After a cytologic report of low grade spindle cell tumor, the node was excised, and a histologic and immunohistochemical diagnosis of intranodal myofibroblastoma was established. CONCLUSION: Intranodal myofibroblastoma should always be considered when aspirating solitary inguinal lymph nodes. The presence of a low grade spindle cell pattern of variably dissociated cells with hemosiderin granules should lead to immunocytochemical studies. Muscle-specific actin expression in the absence of S-100 protein and vascular markers permits a more specific diagnosis.     

Squamous cell carcinoma with metastasis in a cynomolgus monkey (Macaca fascicularis)

A squamous cell carcinoma of the vulva with metastases to the inguinal lymph nodes and lung occurred in a female cynomolgus monkey (Maccaca fascicularis). The primary tumor was a pedunculated mass at the mucocutaneous junction of the left labium anterior to the clitoris.     

Squamous cell carcinoma with metastasis in a rhesus monkey (Macaca mulatta)

A squamous cell carcinoma of the prepuce and penis with metastases to the inguinal lymph nodes and lung occurred in a rhesus monkey (Macaca mulatta). The primary tumor consisted of eroded nodular masses at the mucocutaneous junction of the prepuce and in the epithelium of the prepuce and penis.     

First isolation of Bartonella henselae type I from a cat-scratch disease patient in Japan and its molecular analysis

We isolated Bartonella henselae from an inguinal lymph node of a 36-year-old male patient with cat-scratch disease. The patient had many areas of erythema on his body, swelling of the left inguinal lymph nodes with pain and slight fever. The diagnosis was made on the basis of polymerase chain reaction for B. henselae DNA from the lymph node biopsies and blood sample, and isolation of the organism, histology of the lymph node and serology with an indirect immunofluorescent antibody test. We also analyzed the genome profiles for five strains of 90 isolates from the lymph node by pulsed-field gel electrophoresis after Not I endonuclease digestion. We found two different genomic profiles. These results suggest that the patient had been either co-infected or re-infected with two genetically different strains of B. henselae.     

Evaluation of chromogranin A expression in serum and tissues of breast cancer patients

Human chromogranin A (CgA) is a member of the granin family and is widely distributed in large dense core granules of endocrine and neuroendocrine cells. A variety of non-neuroendocrine carcinomas arising in various tissues show patterns of neuroendocrine differentiation. Expression of CgA has been documented in epithelial cells of normal mammary gland as well as in breast cancers, and elevation of serum CgA has been detected in patients with breast cancer. Our study was undertaken to evaluate the relationship between serum CgA levels and neuroendocrine features in breast cancer. In addition, we evaluated the expression of serum CgA in patients affected by breast cancer compared to controls and the relationship between serum CgA and tumor histology, extent of disease, lymph node status, tumor stage and serum CA 15.3 levels. We enrolled 266 patients with infiltrating ductal or lobular breast carcinoma and a group of 100 age-matched healthy women serving as controls. Serum CgA and CA 15.3 were assayed by specific immunoradiometric methods. The overall sensitivity of CgA and CA 15.3 was 0.06 and 0.34, respectively (chi2 19.1, p<0.0005). No relationship was found between serum levels of CgA and tumor histology, extent of disease, lymph node status or tumor stage while serum levels of CA 15.3 were strongly correlated with all these variables but tumor histology. No relationship was found between serum levels of CgA and CA 15.3. Immunostaining against CgA, CgB, NSE and synaptophysin was performed on primary tumor tissue of 14 serum CgA-positive and 24 serum CgA-negative patients and was negative in all cases. We also evaluated eight cases of pathologically-proven neuroendocrine breast cancer: only four and two of these showed positive CgA immunostaining and increased serum CgA concentration, respectively. In conclusion, serum CgA assay offers no additional information regarding the presence, the extent and the histology of breast cancer compared to the CA 15.3 assay. Moreover, serum CgA was not an accurate marker to identify or exclude the rare neuroendocrine differentiation of breast cancer. We therefore conclude that CgA is not useful as a serum marker in breast cancer.     

Development of an experimental model for spontaneous lymph node metastasis of human esophageal carcinoma in nude mice--histopathological analysis]

Three human squamous cell carcinoma cell lines (HPL-EsC-1-K, -S, and -M) originated from a male patient with esophageal carcinoma were established and were studied on their tumorigenic and metastatic properties in nude mice. All cell lines grew in the hind foot pads following subcutaneous inoculation and produced popliteal lymph node metastasis dose (2-8 x 10(6)/mouse)-dependently. Based on the histopathological findings on serial sections of the lymph nodes, the stages of lymph node invasion by cancer cells were classified into 4 stages (St. 0-III). The time course of lymph node metastasis of EsC-K cells were examined. Advanced stage of metastasis increased according to the time elapsed after tumor cell inoculation. Incidence of metastasis of EsC-K cells were not affected by host factors such as sex differences, anti-asialo GM1 antibody treatment on the hosts. Today, there are few experimental models for studies on spontaneous lymph node metastasis of human carcinomas. This experimental model provides a useful research tool for studies on the biology and therapy for lymph node metastasis of esophageal cancer.     

多品系多部位腹水癌(H22)淋巴转移动物模型的研究

目的：观察多品系小鼠多部位接种H22腹水癌能否引发淋巴结转移,以及它们的差异。方法：选择KM小鼠、BALB／c小鼠、C57BL／6小鼠,分别在腋下、股部内侧和脚垫接种H22腹水癌细胞,观察腋下和腹股沟淋巴结的变化。结果：腋下、股部内侧和脚垫接种组50d动物死亡率分别是：KM小鼠为100％、60％乘0％;BALB／c小鼠为80％、60％和0％;C57BL／6小鼠为100％、50％和0％。试验组动物的淋巴结重量普遍大于空白对照,尤其是KM小鼠和BALB／c小鼠脚垫接种组,病理检查显示,右腹股沟淋巴结可见大量癌细胞淋巴结的正常结构完全被破坏,甚至消失;C57BL,／6小鼠脚垫接种组淋巴结病理检查未发现癌细胞,淋巴结结构完整。结论：KM小鼠、BALB／c小鼠脚垫接种H22腹水癌细胞能够复制存活时间在50d以上,癌细胞发生淋巴结转移的动物模型。     

Fine needle aspiration cytology determinants of the diagnosis of primary nodal Kaposi's sarcoma as the first sign of unknown HIV infection: a case report

BACKGROUND: Kaposi's sarcoma (KS) is a vascular malignant tumor characterized by human herpesvirus 8 infection of neoplastic cells. Diffuse cutaneous lesions represent the classical clinical presentation. This case report describes the first fine needle aspiration cytology findings of a primary lymph nodal KS, a rather unusual localization of the disease. CASE: A 28-year-old, apparently healthy man saw a surgeon for right inguinal node enlargement without other symptoms. The clinician performed fine needle aspiration and made a preliminary diagnosis of a neoplasm of probable mesenchymal origin, not otherwise specified. The lymph node was excised, and the final histologic diagnosis was primary lymphoadenopathic KS. A serologic test revealed antibody positivity for HIV. CONCLUSION: The diagnosis of primary KS of the lymph node, in the absence of any other clinical manifestation, was the first sign of HIV infection.     

Lymphadénite tuberculeuse cervicale simulant une métastase ganglionnaire d’un carcinome papillaire de la thyroïde. À propos d’un cas

Cervical lymph nodes represent one of the most frequent clinical symptoms of extrapulmonary tuberculosis. Their appearance in a neoplastic suggests lymph node metastasis. We report an atypical tuberculous lymphadenetis mimicking lymph node metastasis in a 42-year-old patient followed for papillary thyroid carcinoma operated and treated by iodine 131 therapy. Evolution was marked by the appearance of left cervical adenopathies suggesting lymph node metastatic extension on echographic criteria. A lymph node excision was undertaken and the pathologic study revealed a tuberculous lymphadenitis. The patient was put under antibacillary treatment and evolution was satisfactory. We also expose, through this work, a certain number of techniques of exploration likely to ascertain the diagnosis of a tuberculous lymphadenitis and to monitor the therapeutic strategy.     

Neuroendocrine tumors of gastrointestinal tract in own material

Neuroendocrine tumors are rare gastrointestinal tract disorders, in which diagnosis and treatment are often difficult. The aim of the paper is to present two cases of patients with neuroendocrine tumor of gastrointestinal tract, who underwent surgical procedure in II Department of General and Gastroenterological Surgery of Medical University of Bia?ystok in 2005. A 63-year-old female patient with primary diagnosis of neuroendicrine tumor metastases in liver was not successfully investigated for primary tumor in the preoperative period. The laparotomy procedure indicated the malignant neuroendocrine tumor in the terminal ileum and metastases to the liver and to the greater omentum. The right hemicolectomy and liver metastatic segment VII and VIII resection were performed. The neurological disturbances of obscure origin were observed in the postoperative period and the patient suddenly died on the 15(th) day after surgery. A 57-years-old male patient was operated on for lymph node recurrence of gastric tumor. Pathologic examination of tissue sample revealed the diagnosis of carcinoid. The patient underwent subtotal gastric resection for a pyloric ulcer, diagnosed as Adenocarcinoma G2 pT2N0M0 6 years before. Liver and abdominal node metastases, confirmed by octreoscan, were observed after lymphadenectomy, The treatment of somatostatin analogues (LAR octreotide) was used. In spite of therapy the patient died. The authors present their own experiences and show the preoperative diagnostic difficulties in patients with neuroendocrine gastrointestinal tumors. Unexpected neurological complications in the treatment course were described.     

MAGE-A3/4 and NY-ESO-1 antigens expression in metastatic esophageal squamous cell carcinoma

In the present study we analyzed immunohistochemical expression of MAGE-A 3/4 and NY-ESO-1 in 55 samples of esophageal squamous cell carcinomas (ESCC) and their respective lymph node metastases. To our knowledge this is the first study to assess and compare the expression of these antigens in ESCC lymph node metastases. Fifty (90.9%) primary ESCC were positive for MAGE-A 3/4 and 53 (96.6%) were positive for NY-ESO-1. MAGE-A 3/4 was expressed in all lymph node metastases and the intensity of expression was high in a majority of cases. NY-ESO-1 was negative in 2 (7.1%) lymph nodes metastases, while the reaction was predominantly moderate in the positive group. In primary tumors MAGE-A 3/4 showed a significantly higher intensity of expression compared to NY-ESO-1 (P=0.047), while in lymph node metastases the intensity of expression was not significantly different (P=0.387). Primary tumors with and without lymph node metastases showed no significant differences in MAGE-A 3/4 (P=0.672) and NY-ESO-1 (P=0.444) expression. Intensity of MAGE-A 3/4 (P=0.461) and NY-ESO-1 (P=0.414) expression in primary tumors was not significantly different compared to the expression in their respective lymph nodes metastases. Expression of MAGE-A 3/4 in primary tumors showed significant positive correlation with primary tumor expression of NY-ESO-1 (P=0.021) but no significant correlation with the expression of MAGE-A 3/4 in lymph node metastases (P=0.056). Expression of NY-ESO-1 in primary tumors showed significant positive correlation with the expression of NY-ESO-1 in lymph node metastases (P=0.001) and significant negative correlation with patients’ age (P<0.001). Expression of MAGE-A 3/4 and NY-ESO-1 in primary tumors and lymph node metastases showed no significant correlation with prognostic parameters such as tumor grade and TNM stage (P>0.05). We have shown different levels of MAGE-A 3/4 and NY-ESO-1 expression in almost all specimens of primary tumor and lymph node metastases, suggesting that ESCC may be possible target of immunotherapy and anti-tumor vaccination. High levels of expression in lymph node metastases indicate possible clinical benefit of postoperative vaccine with MAGE-A3 and NY-ESO-1 in advanced stage of disease.     

Model for mediastinal lymph node metastasis produced by orthotopic intrapulmonary implantation of lung cancer cells in mice

This study is designed to establish a pulmonary tumor model to investigate the biology and therapy of lung cancer in mice. Current methods for forming a solitary intrapulmonary nodule and subsequent metastasis to mediastinal lymph nodes are not well defined. Lewis lung carcinoma cell (LLC) suspensions were orthotopically introduced into the lung parenchyma of C57/BL6 mice via a limited skin incision without thoracotomy followed by direct puncture through the intercostal space. The implantation process was performed within approximately 50 sec per mouse, and the operative mortality was less than 5%. Single pulmonary nodules developed at the implanted site in 93% of animals and subsequent mediastinal lymph nodes metastasis were observed in all mice that were succeeded to form a lung nodule after intrapulmonary implantation. The size of tumor nodule and the weight of mediastinal lymph node increased in a time-dependent manner. The mean survival time of mice implanted successfully with LLC cells was 21 +/- 2 days (range; 19-24 days). Histopathological analysis revealed that no metastatic tumor was detectable in the mediastinal lymph nodes on day 11, but metastatic foci at mediastinal lymph nodes were clearly observed on days 17 and 21 after implantation. Other metastases in distant organs or lymph nodes were not observed at 21 days after the implantation. Comparative studies with intrapleural and intravenous injections of LLC cells suggest that the mediastinal lymph node metastasis by intrapulmonary implantation is due to the release of tumor cells from the primary nodule, and not due to extrapulmonary leakage of cells. An intravenous administration of CDDP on day 1 after tumor implantation tended to suppress the primary tumor nodule and significantly inhibited the lymph node metastasis. Thus, a solitary pulmonary tumor nodule model with lymph node metastasis approximates clinical lung cancer, and may provide a useful basis for lung cancer research.     

Cytologic features of metastatic papillary thyroid carcinoma in cervical lymph nodes

OBJECTIVE: To elucidate the cytologic characteristics of metastatic papillary thyroid carcinoma (PTC) in cervical lymph nodes and the differences in cervical lymph nodes from those of stage I (intrathyroidal) PTC. STUDY DESIGN: Forty-seven cases of papillary thyroid carcinoma with cervical lymph node metastasis (group A) and 38 cases of intrathyroidal papillary carcinoma (group B) were included in this study. Preoperative fine needle aspiration cytology (FNAC) examination was performed on enlarged cervical lymph nodes (47 cases, group A) and enlarged thyroid nodules (13 cases, group A, and 38 cases, group B). All the cases were surgically excised and pathologically verified. The cytologic smears were reviewed and analyzed. RESULTS: The cytologic characteristics of metastatic PTC in cervical lymph nodes displayed a higher frequency of foamy macrophages (51.1% vs. 26.3%) and a lower frequency of distinct cell borders (38.3% vs. 71.1%) than those of stage I PTC. Metastatic PTC in cervical lymph nodes also had a higher frequency of cystic degeneration (44.7% vs. 5.3%) than intrathyroidal lesions. In 1 of the 47 cases with lymph node metastasis, the aspirate contained macrophages but no tumor cells. CONCLUSION: FNAC was useful in the diagnosis of metastatic PTC in cervical lymph nodes. However, because cystic degeneration appeared frequently, FNAC combined with thyroid ultrasonography to find the primary lesion is necessary in this situation.     

Detection of Epstein-Barr virus-associated antigen in fine needle aspiration smears from cervical lymph nodes in the diagnosis of nasopharyngeal carcinoma

Epstein-Barr virus (EBV) has consistently been shown to be associated with undifferentiated nasopharyngeal carcinoma, and an EBV-associated nuclear antigen (EBNA) has been detected in the cells of nasopharyngeal carcinoma. A study on the applicability of EBNA detection in fine needle aspiration (FNA) smears from cervical lymph nodes in the diagnosis of metastatic nasopharyngeal carcinoma was performed. All 11 cases (100%) with metastatic nasopharyngeal carcinoma showed EBNA-positive tumor cells, characterized by bright, granulated nuclear fluorescence. Three (50%) of six cases with other metastatic head and neck carcinomas also showed EBNA-positive tumor cells. These findings suggest that the presence of EBNA-positive tumor cells in FNA smears from cervical lymph nodes is not specific for metastatic nasopharyngeal carcinoma. On the other hand, a negative result in the presence of tumor cells may help to exclude it. A larger study is required to verify these preliminary findings.