CD45 (leukocyte common antigen) immunoreactivity in metastatic undifferentiated and neuroendocrine carcinoma: a potential diagnostic pitfall

Leukocyte common antigen (CD45/LCA) and keratin expression are generally mutually exclusive in diagnostic surgical pathology. CD45 reactivity is a reliable indicator of the hematolymphoid nature of a tumor, whereas keratin reactivity is typical of epithelial differentiation (carcinomas and some sarcomas). Some lymphomas, however, might lack detectable CD45 expression, whereas occasional ones might express keratins. CD45 immunoreactivity has been considered exquisitely specific for hematopoietic cells. We report three undifferentiated or neuroendocrine carcinomas that showed membrane-associated immunoreactivity for CD45 in addition to showing distinctive keratin cocktail (AE1/AE3) and epithelial membrane antigen reactivity (all cases); also, keratin 7 was demonstrated in one case and keratin 19 in another. Two cases were lymph node metastases of undifferentiated carcinomas, one of them from the lungs and the other of an unknown origin; the former case showed neuroendocrine features. The third case represented a pulmonary large-cell undifferentiated carcinoma. These cases were negative for lineage-specific leukocyte antigens and did not show clonal immunoglobulin heavy-chain gene rearrangements. Electron microscopic studies demonstrated desmosomes and keratin-like tonofilaments in all three cases, thus confirming the epithelial nature of these tumors. The exceptional membrane staining for CD45 seen in these undifferentiated carcinomas might be comparable to experimentally detected incorporation of leukocyte antigens into the cell membranes of nonleukocytic cells in a leukocyte-rich environment. This rare diagnostic pitfall should be considered in the diagnostic surgical pathology of undifferentiated tumors. It is best avoided by employing a panel of leukocyte and epithelial antigens and by use of electron microscopy, if possible.     

Multiple cutaneous metastases as the first sign of lung cancer in a patient with well-differentiated papillary transitional cell carcinoma of the urinary bladder

A case of multiple, cutaneous metastases as the first sign of lung cancer in a patient with well-differentiated, papillary, transitional cell carcinoma of the urinary bladder is presented. In the left clavicular region were two, sharply demarcated, dark red tumors measuring 3 and 2 cm in diameter with a history of rapid growth and intermittent spontaneous bleeding. Thorough examination of the patient revealed 16 additional skin lesions, which were dark red macules and papules, 2-3 mm in diameter, situated on the left side of the chest. The skin biopsy material (tumors, macular and papular lesions) was studied using histological and immunohistochemical techniques and showed intact epidermis and massive dermal and subcutaneous metastatic involvement by a small cell carcinoma with neuroendocrine differentiation most likely originating in the lung.     

Congenital Y-type urethro-perineal fistula

A case of primary carcinoma of the urinary bladder associated with a primary retroperitoneal leiomyosarcoma is presented. Due to the lack of early symptoms, diagnosis of the retroperitoneal leiomyosarcoma was late and therefore the prognosis was poor. Twelve months after diagnosis the patient died not of the bladder tumor, but of the recurrent leiomyosarcoma.     

Pseudocystic metastases of carcinoma of the uterine cervix mimicking polycystic liver disease

Pseudocystic liver metastases are rare and mainly described in neuroendocrine or ovarian tumors. We report the case of a 46-year-old woman who presented with multiple hepatic metastases mimicking polycystic liver disease. Carcinoma of the uterine cervix had been diagnosed 9 years earlier, and initially treated by radiumtherapy and surgery. Although histological post mortem examination of the pseudocystic liver metastases was not characteristic, they were related to the uterine cervix carcinoma for the following reasons: no other primary tumor was discovered, especially carcinoid or ovarian tumors: immunostains were positive for epithelial cells and negative for the neuroendocrine panel: the cystic cerebellum metastasis had a typical histologic aspect. Uterine cervical carcinoma must thus be included in the list of tumors which may form cystic hepatic metastases.     

Expression of prohormone convertase, PC2, in adrenocorticotropin-producing thymic carcinoid with elevated plasma corticotropin-releasing hormone

An autopsy case of ACTH-producing thymic carcinoid with Cushing's syndrome is reported. The patient was a 63-yr-old man with multiple bone metastases from an undetermined primary site. Hyperpigmentation was observed at the terminal stage. The plasma levels of ACTH, cortisol, chromogranin A, and urinary 17-hydroxy-corticosteroids were extremely high, and ectopic ACTH-producing neuroendocrine tumor was diagnosed. In addition, plasma CRH was high. Autopsy revealed that the patient had primary thymic carcinoid with extensive metastases. Remarkable hyperplasia of the adrenal cortexes and Crooke's hyaline degeneration of the pituitary gland were consistent with Cushing's syndrome by ectopic ACTH production. There were multiple CRH-producing cells without degenerative changes in the hypothalamus. The tumor cells were immunoreactive to ACTH, CRH, and the cleavage enzyme PC2. POMC messenger ribonucleic acid and PC2 messenger ribonucleic acid were detected in the tumor cells by an in situ hybridization method. Expression of PC2 was considered to induce hyperpigmentation by producing alpha MSH. Despite hypercortisolism and ectopic production of CRH by the tumor cells, hypothalamic CRH cells were not atrophic. This case is a good example to demonstrate the correlation between CRH and the hypothalamo-pituitary-adrenal axis as well as hyperpigmentation in Cushing's syndrome.     

Synchronous multifocal development of invasive transitional cell carcinoma of the urinary tract in a patient with renal failure receiving long-term hemodialysis: a case report

We report a case of transitional cell carcinoma in a patient with chronic renal failure receiving hemodialysis for 22 years. A 55-year-old man was admitted to our hospital. Under diagnosis of invasive bladder cancer and left renal pelvic tumor, removal of the whole urinary tract, e.g., bilateral nephroureterectomy and total cystourethrectomy was performed. Transitional cell carcinoma was found in bilateral renal pelvis, left ureter, bladder and prostate in the resected specimen. Thirteen months after the operation, multiple lung metastases and pathologic bone fracture of the 4th lumber vertebra were found. Chemotherapy (3 courses of modified CISCA, consisting of cisplatin, adriamycin and cyclophosphamide) was performed, but the died of systemic metastases of cancer and bleeding due to perforation of multiple gastric ulcers.     

An autopsy case of urinary bladder carcinoma with pulmonary infarction and subacute cor pulmonale caused by tumor embolization

Pulmonary tumor embolism is a common finding at autopsy but is difficult to diagnose clinically antemortem. We report an autopsy case of urinary bladder carcinoma associated with tumor emboli of the pulmonary arteries and subsequent pulmonary infarctions. An eighty-six-year-old man with bloody sputum showed multiple infiltrates on chest X-ray and multiple pleural based parenchymal lesions with truncated apex on computed tomography. The patient had a history of radiation therapy against urinary bladder carcinoma two years earlier. Transitional type carcinoma cells were identified from a urine sample obtained on admission. Three weeks later, the patient developed subacute cor pulmonale and died in severe respiratory distress. Postmortem examination revealed primary carcinoma of the urinary bladder. Multiple tumor emboli of pulmonary arteries and subsequent pulmonary infarctions were visible microscopically. There was a large amount of effusion in both the pleural and the abdominal space. The heart contained focal scarring and mild right ventricular hypertrophy and there was congestion of the lungs, liver, kidneys and spleen. Pulmonary tumor embolization may present at any stage of the patient's illness but rarely causes subsequent pulmonary infarctions. Cytologic examination of blood samples obtained from Swan-Ganz catheters may be useful in the diagnosis of tumor embolization.     

Primary small cell carcinoma of the esophagus with ectopic gastrin production. Report of a case and review of the literature

A case of primary small cell carcinoma of the esophagus in which extensive hormonal studies could be performed is reported. The tumor was considered as a neuroendocrine tumor because the tumor cells showed intracytoplasmic argyrophilia, neurosecretory granules, and positive stain for neuron-specific enolase with Grimelius stain, electron microscopy, and immunohistochemistry, respectively. Furthermore, the tumor was regarded as a gastrin-producing tumor because of positive stain for gastrin in the tumor cells. The present case is the first case of primary small cell carcinoma of the esophagus with ectopic gastric production.     

Determination of erythromycin in urine and plasma using microbore liquid chromatography with tris(2,2''-bipyridyl)ruthenium(II) electrogenerated chemiluminescence detection

Neuroendocrine lung tumors have been considered by some to be a continuum ranging from relatively benign typical carcinoids to highly malignant small-cell carcinomas. Histopathological diagnosis may sometimes be difficult because of their overlapping features. Correct classification, however, carries important prognostic and therapeutic significance. To determine the clinicopathological implications of retinoblastoma (RB) protein expression in these neoplasms, we examined the RB status in a series of neuroendocrine tumors by immunohistochemical analysis of paraffin-embedded tissue sections. A total of 105 tumors were studied. All 44 typical and 15 atypical carcinoids, one of which was initially misdiagnosed as a small-cell carcinoma, manifested a heterogeneous RB-positive staining pattern. Atypical carcinoids in general showed an increase in the number of tumor cells with strong nuclear staining compared to typical carcinoids. In contrast, all 40 small-cell and 6 large-cell neuroendocrine carcinomas failed to show RB staining in any tumor nuclei, indicating loss of RB function. Our results suggest that RB status as measured by immunohistochemical staining can be used as a marker to distinguish typical and atypical carcinoids from small-cell and large-cell neuroendocrine carcinomas.     

Spontaneous regression of pulmonary metastases from transitional cell carcinoma

Spontaneous regression of metastatic cancers occurs rarely and has been reported only once for pulmonary metastases from transitional cell carcinoma. Two cases of spontaneous complete regression of lung metastases from transitional cell carcinoma are presented. In one case, regression occurred after a course of radiation to the primary bladder cancer, but in the other patient, lung lesions disappeared without treatment to the primary or metastatic cancers. The factors that alter the tumor-host relationship to allow spontaneous regression of cancers are unknown, but observation of these phenomena may help reveal parameters that influence tumor progression in the majority of cancer patients.     

Bladder cancer associated with von Recklinghausen's disease: a case report

A 53-year-old man was admitted to our hospital with urinary frequency and miction pain. He had von Recklinghausen's disease with multiple café-au-lait spots and neurofibromatosis. Computed tomography scan and magnetic resonance imaging revealed an invasive bladder tumor 10 cm in diameter, and not metastasis. He was diagnosed as having a bladder tumor (T3a N0 M0 with von Recklinghausen's disease. After balloon occluded arterial infusion (BOAI) chemotherapy, total cystectomy was performed. Pathological diagnosis was transitional cell carcinoma, G3, pT3aN0M0. We reviewed and discussed 97 cases of carcinoma associated with von Recklinghausen's disease reported in the Japanese literature. Only 5 cases of bladder cancer have been reported, including the present case.     

Primary squamous cell carcinoma of the endometrium report of a case and review of the literature

A case of primary pure squamous cell carcinoma of the endometrium in a 50-year-old woman is reported. There was deep myometrial and para-cervical invasion. There is no evidence of metastases 2 years after total hysterectomy and salpingo-oophorectomy and radiation therapy. The patient is probably the youngest suffering from such a tumor. A detailed review of the literature has been carried out.     

Multimodality treatment for gastric carcinoid tumor with liver metastases

Carcinoid tumors are the most common neuroendocrine tumors in the gastrointestinal tract, and between 10% and 30% of these tumors are gastric in origin. Three types of gastric carcinoid tumors are recognized: type I, associated with chronic atrophic gastritis type A; type II, associated with multiple endocrine neoplasia; and type III, sporadic and the most malignant. We present a patient with an aggressive, sporadic-type gastric carcinoid that metastasized to the liver. Her symptomatic treatment included the somatostatin analog octreotide. Octreotide scintigraphy demonstrated that this tumor avidly bound the peptide. The patient's gastric carcinoid (assessed by endoscopy and endoscopic ultrasound) regressed and she underwent hepatic artery embolization for her liver metastases. After initial partial CT resolution the tumor grew, compressing the inferior vena cava. The patient underwent orthotopic liver transplant with excellent recovery, although she was subsequently found to have two small lung metastases. She has responded well to adjuvant Indium-111 octreotide receptor targeted therapy. This case highlights the therapeutic options for metastatic neuroendocrine tumors, including liver transplantation and adjuvant receptor targeted therapy.     

A case of synchronous triple primary cancers of prostate, kidney and bladder

A case of synchronous triple primary cancer occurring in the prostate, kidney and urinary bladder is reported. A 74-year-old man had been complaining of macroscopic hematuria, dysuria and residual sensation of urine since January 1994. Pathological analysis of prostate revealed poorly differentiated adenocarcinoma in March, 1994. Bone and Ga scintigraphy gave no evidence of metastasis. Computerized tomography (CT) revealed irregularity of a part of the margin of prostate (T2N0M0) and enhanced mass with a diameter of 3 cm localized at the hilus of the right kidney. Excretory urography showed a shadow defect in the right pelvis and elevation of the bladder base. In spite of the appearance of class 5 in urine cytology, no tumor was detected in the bladder by cystoscopy. Angiography confirmed the presence of a hypervascular tumor in the right kidney. He underwent right-sided nephroureterectomy in April, 1994, because not only right pelvic tumor but also right renal tumor was suspected. Histological examination of the renal tumor revealed clear cell carcinoma (T2N0M0). Then, he did not visit our hospital for 8 months. In January, 1995 a papillary broadbase tumor was found near the bladder neck by cystoscopy. Transurethral resection of the tumor (TUR-Bt) was performed in February, 1995. Pathological analysis of the tumor revealed TCC G1 pT1 (T1N0M0).     

Effects of nimodipine and isradipine on endothelin-1-induced contraction of pregnant rat myometrium

Bladder malignancy in the renal transplant recipient is an infrequent occurrence. The 11 previously reported cases reflect an aggressive tumor growth with invasion, requiring partial or complete cystectomy with or without conduit diversion. We report an additional case in a 40-yr-old woman with a living related renal transplant, who experienced rapid progression of her tumor over 3 wk from initial hematuria to a pelvic mass involving the anterior bladder. Her allograft ureter and native ureters, as well as her left iliac vein, became obstructed with tumor in another 2 wk. Biopsy showed poorly differentiated, invasive transitional carcinoma. Attempted resection was abandoned because of finding tumor involvement in most of the pelvis. Chemotherapy was not attempted. She died 2 wk after her attempted resection from tumor burden. Our report presents a collective review of these previously reported 11 cases plus our case. These bladder tumors demonstrate a rapid progression of invasive disease and respond poorly to chemotherapy. There is a possible association of bladder tumors with cyclophosphamide immunosuppression. An aggressive surgical approach should be followed, especially since these tumors present in a younger age group.     

Ovarian metastases from cervical carcinomas other than pure adenocarcinomas. A report of 12 cases

Twelve cases of ovarian metastases from cervical carcinomas, most with clinical manifestations of ovarian involvement, are reported. The patients were 23-73 years of age (average, 43 years). The ovarian and cervical tumors were synchronous in eight patients; in three, ovarian tumors were discovered 10 months, 2.5, and 3 years after the detection of a cervical neoplasm. In one patient, the cervical tumor was not discovered until autopsy 7 months after presentation. Four patients had abdominal swelling or distention, three had vaginal bleeding, three had an abnormal Papanicolaou smear, and two had masses discovered during pelvic examination. The ovarian tumors, six of which were bilateral, ranged from 5-17 cm (average, 9.5 cm) in maximal dimension in 11 patients; in the 12th patient, the involved ovary was not enlarged. The cervical tumors were grossly evident in 10 patients. They were usually deeply invasive, often with extracervical extension. Four were squamous cell carcinomas; two, small cell carcinomas; one, a mixed small cell carcinoma and adenocarcinoma; one, a mixed poorly differentiated carcinoid and adenocarcinoma; two, adenosquamous carcinomas; one, a transitional cell carcinoma; and one, an undifferentiated carcinoma. Various features, including bilaterality of the ovarian tumors, the finding that the histologic features of the ovarian tumors typically were unusual for a primary ovarian neoplasm, and the presence of extensive extracervical disease, led to the conclusion that the ovarian tumors were metastatic from the cervix. Although ovarian metastases of cervical carcinoma are uncommon, this series illustrates that, occasionally striking examples with clinical manifestations of ovarian involvement occur.     

Primary round-cell liposarcoma of the bladder

OBJECTIVE: To report a rare case of primary round cell liposarcoma of the urinary bladder. METHODS: A case of primary round cell liposarcoma of the urinary bladder in an 80-year-old female with hematuria is presented. The patient had a large, solid, non-circumscribed bladder tumor of 6.5 cms. The radiological, histological and immunohistochemical findings are discussed. RESULTS: The neoplasm was composed of isolated lipoblasts among numerous small round cells that were positive for S-100 and vimentin, and a high proliferation rate was demonstrated by Ki-67. The patient died 10 months after the histologic diagnosis. CONCLUSION: Primary liposarcoma of the urinary bladder is a very rare tumor with a poor prognosis that usually presents as a large tumor mass.     

Different techniques of internal fixation applied in lumbosacral fusion: 83 cases analysis

To characterize the cytologic spectrum of small cell carcinoma of the urinary bladder, a review of 42 urinary cytology specimens from 13 patients with histologically proven tumors was conducted. Patients ages ranged from 45 to 81 yr (mean 68.9). In four tumors, small cell carcinoma was the sole malignant cellular component: all 11 urinary specimens in these patients harbored cells with features of an undifferentiated small cell carcinoma. In the remaining nine tumors, small cell carcinoma appeared with transitional, squamous cell or adenocarcinoma, but in four, small cell carcinoma was the sole invasive component. Almost one third of urinary specimens in this group lacked a small cell component. Neuroendocrine differentiation was confirmed by immunopathology in eleven cases (neuron specific enolase positive in 11 of 12, synaptophysin in 2/11, chromogranin in 2/13, Leu 7 in 2/7), and by ultrastructural analysis in two. Small cell carcinoma is a cytologically recognizable variant of bladder cancer, but admixture with other malignant components may mask its appearance in urinary specimens.     

Primary heterologous carcinosarcoma (metaplastic carcinoma) of the urinary bladder: a clinicopathologic, immunohistochemical, and ultrastructural analysis of eight cases and a review of the literature

BACKGROUND: Heterologous carcinosarcomas of the urinary bladder are rare neoplasms, the histogenesis of which is still disputed. METHODS: The clinicopathologic, immunohistochemical, and ultrastructural features of eight cases were analyzed. RESULTS: The patients, 5 males and 3 females, had a median age of 70 years. Gross hematuria, dysuria, and urinary tract infections were the main presenting symptoms. Tumors were solitary in all cases and located in the right wall in six cases. Tumor size ranged from 2 to 12 cm (median, 5 cm). Four patients died of disease 2, 6, 17, and 42 months postoperatively, respectively. Microscopically, the tumors consisted mostly of a varied mixture of high grade transitional cell carcinoma with chondrosarcoma, osteosarcoma, rhabdomyosarcoma, and undifferentiated spindle cell (leiomyosarcoma-like) components with occasional transitional features between one component and another. All tumors but one invaded the muscularis propria or the perivesical fatty tissue. Immunohistochemically, keratin expression was observed focally in the sarcoma component as well as the carcinoma component. Reactivity for vimentin, desmin, muscle specific actin, and S-100 protein was observed in poorly differentiated areas in addition to the expected positivity of each histologic subtype of sarcoma. Ultrastructurally, one tumor showed evidence of both epithelial and chondrosarcomatous differentiation, whereas three contained rhabdomyosarcomatous elements. CONCLUSIONS: On the basis of the current series and a review of 55 reports from the literature, primary heterologous carcinosarcoma of the urinary bladder proved to be a highly malignant type of neoplasm occurring predominantly in elderly males that was most often in an advanced stage at presentation and rapidly became lethal. Histogenetically, some heterologous carcinosarcomas should be regarded as a variant of sarcomatoid carcinoma (metaplastic carcinoma) that shows prominent heterologous differentiation.     

Undifferentiated pancreatic cancer associated with humoral hypercalcemia of malignancy

We present a case of undifferentiated pancreatic cancer associated with humoral hypercalcemia of malignancy (HHM) in which parathyroid hormone-related protein (PTH-rP) is identified as the causative factor of hypercalcemia. A 61-year-old man was hospitalized with right hypochondralgia. Ultrasound examination and computed tomography demonstrated a large mass in the pancreatic head with liver metastases. Biopsy of the pancreatic tumor demonstrated undifferentiated carcinoma. Serum calcium level and PTH-rP were elevated. Bone scan with technetium-99 demonstrated no accumulation in the bones. Immunohistochemical staining for PTH-rP was weakly positive in the tumor cells. We considered that PTH-rP was the causative factor of HHM in this case from laboratory data and immunohistochemical findings. This rare case was successfully treated with pamidronate disodium, which is a type of bisphosphonate derivative. We compared this case with previously reported cases.