Recurrence of primary hepatic carcinoid tumor in the remnant liver 13 yr after resection

We report here a case of primary hepatic carcinoid tumor (PHCT) recurring in the remnant liver 13 yr and 10 mo after first resection. A 70-yr-old man developed four hypervascular tumors in the liver in December 2003. He had undergone curative left-lobe hepatectomy for PHCT in February 1990. Histopathological examination of the tumor biopsy specimen showed that the tumor was composed of uniform round-to-oval cells with solid arrangement and the tumor cells stained positive for chromogranin A, synaptophysin, and neuron-specific enolase. We diagnosed this case as an intrahepatic metastasis of PHCT with a long latency period, based on the fact that no primary site of carcinoid tumor could be found despite intensive examination and the immunohistochemical findings of the resected tumors were essentially same as those of PHCT in 1990. Although PHCT is reported to have a more favorable prognosis than other hepatic cancer or metastatic carcinoid tumor in the liver, long-term observation is recommended.     

原发性肝脏类癌的诊断一例报道

Primary hepatic carcinoid tumor (PHCT) is a extremely rare neoplasm, usually lacking specific symptoms. We present a histologically proved case and review the cases in the literature. The patient was an 65-year-old man with right upper abdominal pain and weight loss who underwent exploratory laparotomy for huge mass of the liver. Ultrasonography showed a well-demarked, cystic mass with irregular thick wall, whereas CT revealed a low-density tumor in nephrographic phase and peripheral enhanced areas in artery phase. He was diagnosed as PHCT by histological findings including positive staining of tumor cells for chromogranin A and synaptophysin, and no evidence of other primary source of tumor. Thus, a patient with this type of mass showed by imaging examination should be suspected of PHCT, for it is of great importance to clinical treatment.     

Signet-ring cell carcinoid: a primary hepatic carcinoid tumor with cytoplasmic inclusions comprising of aggregates of keratin.

A case of primary hepatic carcinoid tumor was recently encountered, which was argyrophil and showed positive reactions to serotonin, gastrin and pancreatic peptide in an immunohistochemical hormonal study. The tumor had unusual morphologic features. The neoplastic cells had a signet-ring cell appearance, similar to the signet-ring cells normally seen in mucin-producing adenocarcinoma. Ultrastructural and immunohistochemical studies revealed the formation of the signet-ring cells to have been caused by the presence of cytoplasmic inclusions consisting of cytokeratins. Further investigation, using eight monoclonal antibodies recognizing cytokeratins of different molecular weights, showed the accumulated cytokeratins to be of low and medium molecular weights. The morphologic observations in this unusual case of hepatic carcinoid tumor are described and reported cases with similar features, for which we propose the term "signet-ring cell carcinoid," are reviewed.     

Primary mucinous carcinoid tumor of the ovary

A case of primary mucinous carcinoid tumor of the ovary occurring in a 37-year-old woman is described. The tumor, which replaced the left ovary, was accompanied by metastases in the contralateral ovary and para-aortic lymph nodes. Careful investigations excluded metastatic origin of the tumor. The tumor was solid, but contained an epidermoid cyst. There were no other teratomatous elements. The patient was treated with combination chemotherapy. A second-look operation 9 months following diagnosis revealed extensive microscopic involvement of the peritoneal cavity. The patient's condition deteriorated and she died 1 year after diagnosis. Detailed autopsy revealed peritoneal, pleural, lymphatic, and bone marrow carcinomatosis, but no evidence of a primary tumor elsewhere. Microscopic, ultrastructural, and immunocytochemical findings are described. It is considered that primary mucinous carcinoid tumor of the ovary represents a specific histopathologic entity. Unlike other types of primary ovarian carcinoid tumors, it behaves as an aggressive malignant neoplasm.     

A case report of primary hepatic carcinoid with lymph node metastasis--treatment of hepatic arterial infusion to post-reoperative liver and radiation to metastasis of para-aortic lymph nodes

We report a case of primary liver carcinoid. A 50-year-old woman had undergone left nephrectomy six years earlier for renal cell carcinoma. She developed abdominal pain. CT scans showed a low-density area in the lateral segment of the liver and lymph node swelling to the left of the abdominal aorta. Angiography showed a hypovascular tumor. After lateral segmentectomy and examination of the gastrointestinal tract, we diagnosed primary liver carcinoid. Unfortunately, the tumor recurred at multiple sites in the residual liver about 9 months after the first operation. She underwent further liver resection and microwave coagulation therapy. At that time, lymph node biopsy confirmed metastatic carcinoid. We began hepatic arterial chemotherapy for the residual liver and radiation therapy for the para-aortic lymph nodes (total 45 Gy). During chemotherapy, no recurrence was seen. At 11 months after reoperation, however, multiple liver metastases occurred with severe liver dysfunction and jaundice. She died about 24 months after the first liver resection.     

Cervical metastases from small bowel carcinoid tumors

Small bowel carcinoid tumors usually metastasize to regional lymph nodes and the liver but metastases to the neck are extremely rare. Over a ten-year period 48 cases of small bowel carcinoid were diagnosed at our institution and of these, three cases (6%) were associated with neck metastases--one to the thyroid gland and two to cervical lymph nodes. The former patient and one of the latter patients had symptoms of the carcinoid syndrome. The other patient was asymptomatic and presented with a solitary neck mass. Urine levels of 5-hydroxyindolacetic acid (5-HIAA) were elevated in the two symptomatic patients but were undetectable in the asymptomatic patient. Extirpation of the involved cervical nodes and the primary small bowel lesion was performed in two patients. In addition, both patients have received chemotherapy with 5-fluorouracil. One patient remains asymptomatic four years after diagnosis but the other patient continues to have five to six bowel movements per day nine months after operation. Small bowel resection was performed in the patient with a metastasis to the thyroid. This patient died of sepsis after a second operation for an intraabdominal abscess. The histological patterns of the primary tumor and the metastatic lesions were similar and the cells of the metastases contained argentaffin-positive granules. We conclude that 1) an intraabdominal carcinoid tumor should be considered as the location of the primary tumor in patients who present with a neck mass containing metastatic carcinoid and 2) the prognosis for patients with extraabdominal metastases is similar to that for patients with intraabdominal disease only.     

A case of primary carcinoid tumor of the testis

A case of a primary carcinoid tumor of the testis which occurred in a 57-year-old man is reported. The patient was treated by orchiectomy, and no clinical features of a carcinoid syndrome had been noted. The tumor measured 4.0 X 3.2 X 2.0 cm in size and was yellowish in color. Histochemically, the tumor cells were composed in part of argentaffin and in part of argyrophil. Immunohistochemically, the argentaffin tumor cells were positive for neuron-specific-enolase. No tumor cells were positive, however, for neurofilaments, vimentin, keratin, desmin, GFAP, S-100 protein, ACTH, and somatostatin. Electronmicroscopy revealed numerous neurosecretory granules. Tumorous tissue presented a histomorphology of a pure carcinoid tumor composed of parts of argentaffin and argyrophil.     

Non-functional pancreatic endocrine carcinoma with multiple liver metastases--a case report

A 60-year-old woman was admitted to our hospital because of upper abdominal discomfort and body weight loss. Abdominal CT showed multiple liver tumors with early enhancement and delayed washout. There were no abnormal findings in other organs. IVR-CT showed hypervascular masses, but it is not a typical tumor staining of HCC. To obtain the diagnosis, we performed laparoscopic partial liver resection in the left lateral segment. Histological examination suggested a primary hepatic carcinoid a tumor. But primary hepatic carcinoid tumor is comparatively rare, so we underwent further examinations. Two months later after the liver resection, the tumor of pancreatic tail was detected by CT and MRI. We could obtain the diagnosis of pancreatic endocrine tumor by EUS-FNA. We conducted a distal pancreatectomy with splenectomy and partial colonic resection. She had no symptom related to neuroendocrinology. The final diagnosis was non-functional endocrine carcinoma of pancreas. After that, we added extended right hepatic lobectomy with radiofrequency ablation in left lobe. The woman remains alive without a recurrence after the surgery.     

Norepinephrine-producing tumors of bilateral breasts: a case report

There was a tumor in the left breast which was suspected to be carcinoid tumor at excisional biopsy. Autopsy revealed the same tumor in the right nipple. In the cells of the bilateral tumors a number of argylophil granules were diffusely demonstrated and the neurosecretory ones were verified electronmicroscopically. In the urine of the patient a moderate amount of norepinephrine was excreted. It was presumed that the norepinephrine might have been produced from the breasts. In the literature reviewed, the case of breast carcinoid has not been reported previously.     

Primary carcinoid tumor of the testis: case report, ultrastructure and review of the literature.

A case of primary pure carcinoid tumor of the testis which occurred in a 71-year-old male is reported. The patient was treated by radical orchiectomy and remains well and symptom free 10 months after operation. Histologically as well as ultrastructurally the tumor showed typical appearances of carcinoid tumor of midgut derivation. 23 cases of carcinoid tumors of the testis were discovered in the literature. Of these 17 were primary testicular carcinoids, and 6 were metastatic to the testis. Of the 17 cases of primary carcinoid tumors, 14 were pure carcinoids and only 3 were associated with teratoma. None of the primary testicular carcinoids were associated with metastases and the prognosis after orchiectomy was excellent, thus indicating that no further therapy is necessary. The prognosis of patients with carcinoid metastatic to the testis is poor. In view of this it is very important to determine whether the tumor is primary or metastatic.     

Pulmonary carcinoid presenting as multiple subcutaneous nodules

A 60-year-old female presented with a one-year history of multiple enlarging tender subcutaneous nodules. Initial biopsy demonstrated a poorly differentiated adenocarcinoma. Mammography showed multiple nodular breast lesions. After the patient failed to respond to tamoxifen, a second biopsy demonstrated a metastatic carcinoid tumor. Further search revealed a single small pulmonary nodule, which on aspiration biopsy proved to be a carcinoid tumor. The patient failed to respond to treatment with streptozotocin and 5'-fluorouracil. Therapy with leucovorin calcium and 5'-fluorouracil then produced a partial response.     

Treatment of metastasized carcinoid tumor of the ileum and cecum with recombinant alpha-2b interferon

Seven patients with progressive ileal or caecal carcinoid tumors and liver metastases were treated with human recombinant alpha-interferon (IFN alfa-2b) at a dosage of 2-4 x 10(6) U daily or every other day subcutaneously. Six patients had symptoms of the carcinoid syndrome. No change of tumor size lasting 4 to 40+ months (median, 18 months) was noted in 6 patients, and 1 patient had hepatic tumor progression. A decrease in urinary excretion of 5-hydroxyindoleacetic acid by more than 50% lasting 2-11 months (median, 4) was observed in 5 patients. Four patients were completely or partially relieved of flushing, diarrhea, obstruction or abdominal pain. The side-effects were negligible with the exception of mild fever, headache and confusion only during the first days of therapy. Treatment with IFN alfa-2b offers good palliation to patients with disseminated ileal or caecal carcinoid tumor and carcinoid syndrome.     

Rounding of cultured human carcinoid tumor cells by forskolin

A primary culture of carcinoid cells obtained from a metastasized brain tumor of a 30 year old man was established. Rounding of carcinoid cells was induced by the addition of 20 microM forskolin or 1 mM dibutyryl cyclic AMP to the culture medium. The cyclic AMP content in carcinoid cells was increased thirtyfold by the addition of 20 microM forskolin. The results provided evidence that cyclic AMP might also be involved in rounding of human malignant carcinoid cells.     

Transrectal Ultrasonography of a Small Rectal Carcinoid Tumor with Lymph Node Metastasis: A Case Report

A 27-year-old woman with a small rectal carcinoid tumor wasexamined by transrectal ultrasonography (TRUS) for preoperativestaging. TRUS revealed regional lymph node involvement, in additionto a 10-mm hypoechoic tumor invading into, but not through,the submucosa. The lymph node involvement was confirmed preoperativelyby TRUS-guided needle biopsy. Although the digital examinationfindings indicated local excision was appropriate, in accordancewith TRUS and TRUS-guided biopsy findings, the patient underwentradical surgery. The TRUS findings of lymph node involvementand depth of invasion were confirmed histologically. The patientis alive and disease-free 35 months postoperatively. These observationssuggest that TRUS reveals the regional lymph node involvementand the depth of invasion of rectal carcinoid tumors accuratelyand, therefore, helps in selecting appropriate treatment.     

The aromatic-L-amino acid decarboxylase inhibitor carbidopa is selectively cytotoxic to human pulmonary carcinoid and small cell lung carcinoma cells.

The carcinoid tumor is an uncommon neuroendocrine neoplasm the hallmark of which is excessive serotonin production. In studying kinetics of tryptophan hydroxylase and aromatic-L-amino acid decarboxylase (AAAD) in human carcinoid hepatic metastases and adjacent normal liver (J. A. Gilbert et al, Biochem. Pharmacol., 50: 845-850, 1995), we identified one significant difference: the Vmax of carcinoid AAAD was 50-fold higher than that in normal liver. Here, we report Western and Northern analyses detecting large quantities of AAAD polypeptide and mRNA in human carcinoid primary as well as metastatic tumors compared with normal surrounding tissues. To assess the feasibility of targeting these high AAAD levels for chemotherapy, AAAD inhibitors carbidopa (alpha-methyl-dopahydrazine), alpha-monofluoromethyldopa (MFMD), and 3-hydroxybenzylhydrazine (NSD-1015) were incubated (72 h) with NCI-H727 human lung carcinoid cells. Carbidopa and MFMD were lethal (IC50 = 29 +/- 2 microM and 56 +/- 6 microM, respectively); NSD-1015 had no effect on proliferation. On exposure to other human tumor lines, carbidopa was lethal only to NCI-H146 and NCI-H209 small cell lung carcinoma (SCLC) lines (IC50 = 12 +/- 1 microM and 22 +/- 5 microM, respectively). Carbidopa (100 microM) decreased growth of (but did not kill) SK-N-SH neuroblastoma and A204 rhabdomyosarcoma cells and did not affect proliferation of DU 145 prostate, MCF7 breast, or NCI-H460 large cell lung carcinoma lines. The rank order of lines by AAAD activity was NCI-H146 > NCI-H209 > SK-N-SH > NCI-H727, whereas A204, DU 145, MCF7, and NCI-H460 had no measurable activity. For lung tumor lines (carcinoid, two SCLC, and one large cell lung carcinoma), AAAD activity was correlated with the potency of carbidopa-induced cytotoxicity. However, carcinoid cell death was not solely attributable to complete inhibition of either AAAD activity or the serotonin synthetic pathway. In further evaluating potential applications of these findings with carbidopa, we determined that sublethal doses of carbidopa produced additive cytotoxic effects in carcinoid cells in combination with etoposide and cytotoxic synergy in SCLC cells when coincubated with topotecan.     

A case of gastric carcinoid tumor with coexisting adenocarcinoma in the same tumor

A case of a gastric carcinoid tumor with a coexisting adenocarcinoma in the same tumor is reported. The patient was a 71-year-old man who complained of epigastralgia. His physical examination and routine laboratory data were unremarkable. An upper GI x-ray series and the gastroendoscopic findings, however, demonstrated a Borrmann 2-like tumor of the antrum. An endoscopic biopsy specimen from the tumor revealed that it was a gastric adenocarcinoma. Therefore, a subtotal gastrectomy with a lymph node dissection was performed. The resected specimen showed a Borrmann 2-like tumor, but also that infiltration was limited to within the submucosal layer. The pathological findings revealed that the tumor contained two differential component structures (a carcinoid and an adenocarcinoma). The carcinoid and adenocarcinoma structures coexisted with transitional changes that connected both structures. Pathohistologically, it was thought that these two differential components developed from a common origin.     

原发性睾丸类癌1例报告并文献复习

目的探讨原发性睾丸类癌的发生机理、临床病理特点、诊断和鉴别诊断。方法对1例术前诊断为睾丸肿瘤患者,行患侧根治性睾丸切除术。结果术中发现左侧精索、睾丸、附睾鞘膜光滑,与周围组织无黏连浸润,术后纵行剖开肿物见附睾头呈囊性,大小为4.5 cm×3.5 cm,切开囊肿内含黄色混浊液体,量约20 ml。左侧睾丸直径约3.5cm,内有一灰白色占位,大小约2.3 cm×2.0 cm。结论原发性睾丸类癌是1种罕见的睾丸肿瘤,分单纯性类癌和畸胎瘤类癌2种,需与其他睾丸肿瘤鉴别。     

Adenocarcinoma adjoining to the gastric antrum and minute carcinoid--a case report

The simultaneous occurrence of carcinoma and carcinoid in the stomach is rare. Only 5 cases have been reported in the literature so far. Our patient developed double primary neoplasms adjoining the gastric antrum. One was an early ulcerated adenocarcinoma limited to the submucosa, the other a minute carcinoid also within the submucosa. A large amount of 5-HIAA, but a normal amount of histamine, was excreted in the urine. The carcinoid syndrome, however, was absent through clinical course. The patient died of liver metastasis 3.5 months after gastrectomy. Microscopic examination after autopsy disclosed that the metastases consisted of only carcinoid cells.     

Minute gastric carcinoid tumor with regional lymph node metastasis

We report a patient with a minute gastric carcinoid tumor with lymph node metastasis, and a small gastric cancer. A 50-year-old man having a diagnosis of an elevated lesion on the anterior wall of the gastric body, detected by a series of upper gastrointestinal examinations, was referred to the Cancer Institute Hospital. Careful upper fluoroscopy disclosed a small superficial depressed lesion with converging folds and a superficial elevated lesion covered with nonspecific gastric mucosa. With a final preoperative diagnosis of depressed early cancer and minute carcinoid tumor of the stomach, made by upper gastrointestinal examinations including biopsy, the patient underwent segmental gastrectomy and perigastric lymph node dissection. Histological examination of the resected specimen revealed a lymph node metastasis from a gastric carcinoid tumor of 5-mm diameter, in addition to an early gastric cancer of poorly differentiated adenocarcinoma. Small gastric carcinoid tumors have been regarded as being benign neoplasms biologically. However, the case we present suggests that attention should be paid to the possibility of metastasis at the time of treatment for a minute sporadic gastric carcinoid tumor. We therefore discuss the malignant potential of these tumors, mainly from the viewpoint of histopathological classification, to gain understanding so that the patients can be treated adequately.