Bronchial carcinoma and hypercalcaemia

Hypercalcaemia due to malignant disease, in the absence of bone metastases, is generally regarded as a rare event. It occurred in 16% of a series of cases of bronchial carcinoma coming to necropsy. Hypercalcaemia is a relatively common complication of bronchial carcinoma.The hypercalcaemia is usually accompanied by hypophosphataemia and, in this respect, must be distinguished from the hypercalcaemia that may be found with breast carcinoma. It is frequently accompanied by hypokalaemic alkalosis; this must not be confused with the metabolic disorder that results from the production of ectopic ;ACTH'.The bones sometimes show changes of osteitis fibrosa akin to those seen in hyperparathyroidism. Cystic disease of bone recognizable radiologically is rare, probably because of the relatively short duration of the metabolic disturbance.The parathyroids are usually mildly atrophic. There is no evidence that the main pathogenetic mechanism is stimulation of the parathyroids by the tumour. Acceptable instances of parathyroid hyperplasia are very rare: the significance of these exceptional cases awaits further study.Squamous carcinoma of the bronchus is the type mainly incriminated. Oat-cell carcinoma and bronchial adenocarcinoma are involved less frequently than expected by chance. The significance of the tumour types implicated is discussed in relation to the possible pathogenesis.     

Myospherulosis in renal cell carcinoma

OBJECTIVE: To study retrospectively the identification, characteristics, and localization of myospherulosis in different types of renal cell carcinomas. DESIGN: Twenty-seven consecutive renal cell carcinomas treated by radical nephrectomy in 1 year were studied. All the tumor and nontumor slides were examined for myospherulosis. The demographic data, histological type of renal cell carcinoma, Robson stage, and Fuhrman grades were recorded. RESULTS: Myospherules were found in 10 cases. They were associated with the clear cell type and a higher nuclear grade. The cell type remained the only significant factor when these 2 factors were tested together with the tumor stage by logistic regression. Myospherulosis tended to be found in younger patients but was not associated with the sex or the side of the tumor. They were scattered within tumor cystic spaces or among sheets of tumor cells. Some of the myospherules might arise from histiocytes or even tumor cells. Compared with previous reports of myospherulosis associated with exogenous or endogenous lipid, the myospherules associated with renal cell carcinoma were smaller and more uniform in size. There is no associated fibrosis or foreign body giant cell reaction. CONCLUSION: As far as we know, this is the first report of myospherulosis occurring in malignant tumors in human, and their associated features are different from those previously described for myospherulosis related to exogenous or endogenous lipid.     

Chromophobe renal cell carcinoma

Chromophobe renal cell carcinoma (RCC) is a recently established subtype of RCC, which has rarely been reported in Japan. In this communication, the authors report two Japanese cases of chromophobe RCC together with the immunohistochemical findings. The tumors were composed of sheets and cribriform glands formed by tumor cells with cloudy and reticular cytoplasm. Ultrastructurally, the cytoplasm was filled with numerous microvesicles. The tumor cells were positive for cytokeratin, epithelial membrane antigen, and Tamm-Horsfall protein. Occasionally, LeuM1-positive cells were also noted. Vimentin was negative, unlike the usual RCC. Reactivity for peanut agglutinin was more frequent than that to Lotus tetragonolobus agglutinin. The results of this study suggest that the tumor cellq possessed phenotypes similar to the distal nephron rather than to the proximal tubular cells.     

Papillary renal cell carcinoma

A series of 43 papillary renal cell carcinomas (PRCCs) were analyzed to investigate the prognostic value of the morphological subtyping (type 1/type 2) proposed by Delahunt and Eble. Twenty-six cases were type 1 (small cuboid cells arranged in single or double layers), 13 cases were type 2 (voluminous eosinophilic cells with irregular pseudostratification pattern), and four cases with oncocytic cells (large eosinophilic cells with round regular nuclei) were distinct from type 2 and grouped apart. All type-1 and oncocytoid-type PRCCs were staged pT1 or pT2, whereas 8/13 type-2 PRCCs were staged pT3 or pT4. Follow-up information (range, 3-113 months; median, 43 months) showed 12 deaths from disease: 2 in the type-1 group,10 in the type-2 group, 0 in the oncocytoid-type group. The Kaplan-Meier analysis showed that pejorative outcome was associated (P<0.001) with high stage (pT3/pT4), high nuclear grade (3/4), morphological type 2, absence of foam cells, and abundant fibrous stroma. The multivariate analysis showed that stage and morphological type were independently associated with survival (P<0.05). These results support the clinical interest of morphological subtyping of PRCCs in the prognosis evaluation of the patients. The four oncocytoid-type PRCCs had a favorable outcome, but additional data are required to evaluate this type of neoplasm.     

Ipsilateral synchronous renal cell carcinoma and transitional cell carcinoma.

The simultaneous occurrence of renal cell carcinoma(RCC) and transitional cell carcinoma(TCC) in the same kidney is unusual. We report a 53-year-old man with ipsilateral synchronous renal adenocarcinoma and renal pelvic transitional cell carcinoma with severe hypercalcemia and a huge staghorn calculus in the opposite kidney. The patient was admitted to the hospital because of left flank pain and intermittent fever which he had had for 2 months. Computerized tomography revealed a huge stone in the right kidney and a mass in the upper pole with an irregular calcified pelvis in the left enlarged kidney. Left radical nephrectomy was done. A section of the specimen revealed a renal cell carcinoma located at the upper pole and a papillary transitional cell carcinoma arising from the renal pelvis. This is a rare case of combined renal malignancies.     

Enolase isozymes in renal tubules and renal cell carcinoma.

To elucidate the localization of enolase isozymes in renal tubules and renal cell carcinoma, an immunohistochemical study and quantitative analysis by employing the enzyme immunoassay were performed. The alpha-enolase was localized in almost all epithelial cells of renal tubules except for loops of Henle. The gamma-enolase was localized in macula densa cells and epithelial cells of loops of Henle and collecting ducts of the medulla, but not in those of proximal tubules. In renal cell carcinoma, most tumor cells possessed two enolase isozymes. From these immunohistochemical findings, it is suggested that enolases are present mainly in the alpha alpha form in epithelial cells of proximal tubules, in the gamma gamma form in those of loops of Henle, and in the two forms and/or the alpha gamma form in tumor cells of renal cell carcinoma. The levels of gamma-enolase in the normal cortex were 16.8 +/- 3.7 ng/mg protein (n = 7), whereas those in renal cell carcinoma were 928 +/- 554 ng/mg protein (n = 7), about 55-fold higher than those in the normal cortex. The serum gamma-enolase levels were also enhanced in 20 (49%) of 41 patients with renal cell carcinoma. Because it is generally accepted that renal cell carcinoma is derived from epithelium of proximal tubules, the expression of gamma-enolase has occurred during carcinogenesis.     

Immunohistochemistry and lectin histochemistry in sarcomatoid renal cell carcinoma: a comparison with classical renal cell carcinoma

We investigated the expression of various cell markers in renal cell carcinoma, concentrating particularly on the sarcomatoid variety, using lectin and immunohistochemical techniques. The sarcomatoid variant showed stronger staining in a higher proportion of cases for vimentin and reduced positivity for epithelial membrane antigen, in comparison with classical renal cell carcinoma. All sarcomatoid tumours reacted with at least one cytokeratin, enabling them to be distinguished from true renal sarcomas; this is of diagnostic value when a panel of markers is used. Overall a similar pattern of markers is seen in sarcomatoid and classical renal cell carcinoma using lectin and immunohistochemistry, suggesting that the sarcomatoid variant arises as a metaplastic change rather than having a different histogenesis.     

GATA3 aids in distinguishing fumarate hydratase-deficient renal cell carcinoma from papillary renal cell carcinoma

GATA3 has been reported to be positive in clear cell papillary renal cell carcinoma and papillary renal neoplasm with reverse polarity. However, its features in high-grade RCC remain unclear. Despite the emergence of novel renal entities, FH-deficient RCC remains one of the most aggressive renal neoplasms. The diagnosis is mainly based on the loss of FH at the protein level. Previous studies have shown that inclusion-like nuclei, multiple architectural patterns, FH loss, and 2SC positivity can differentiate FH-deficient RCC from other RCC. In some FH-deficient RCC cases, FH is normally expressed and is difficult to diagnose. This study included 11 FH-deficient RCC, and GATA3 showed different expression in seven cases. However, 147 papillary renal cell carcinomas were included, and GATA3 expression was negative. A comparison of clinicopathological aspects between 11 FH-deficient RCC and 30 high-grade PRCC showed statistical significance in age, size, multiple architectural patterns, inclusion-like nuclei, and prognosis. However, PRCC exhibited similar characteristics. CK7, GATA3, and FH profiles were also statistically significant. Different chromosomal alterations were found in FH-deficient RCC, and chromosomal alterations were not different between FH-deficient RCC and PRCC. GATA3 was positive in 33 % (7/21) of collecting duct carcinomas and negative in other high-grade renal neoplasms. GATA3 is negative in PRCC, but can be positive in FH-deficient RCC and collecting duct carcinoma. GATA3 expression may indicate a worse outcome in high-grade RCC with papillary architecture. We recommend GATA3 IHC for the differential diagnosis and prognostic assessment of high-grade RCC with papillary architecture.     

Renal immunopathology in renal cell carcinoma

Summary Signs of glomerulopathy, especially a nephrotic syndrome can occur in cancer patients, but the exact frequency of glomerular lesions is not well known in these patients. To define this frequency in a given type of malignancy we have studied the nephrectomy kidneys in 40 patients with renal cell carcinoma. Proteinuria, which was present in 7 cases, ranged from 0.15 to 1.5 g per 24 h. Reduction of the creatinine clearance greater than 50% was observed in 5 patients. Circulating immune complexes were detected in 11 of the 15 patients studied. Carcinoembryonic antigens were noted in 2 of 9 patients investigated. Research of alpha 1 foetoprotein carried out in 12 patients was always negative. HBs antigen or Hbs antibodies were detected in 6 of 29 patients studied. Light microscopic examination of the normal uninvolved kidney tissue showed obvious glomerular lesions (mesangial hypertrophy with or without deposits, with or without cell proliferation) in 7 patients (17.5%). Amyloid deposits were never observed. Immunofluorescence study revealed mesangial deposits in 35% of patients versus 5.4% of control subjects (P < 0.0001). These deposits included C3 and/or IgM in 13 cases, IgA and C3 in one case. No fixation was observed, neither on tubules of normal tissue nor on carcinoma lesions. This report demonstrates that glomerular deposits are usually found in approximately one third of patients with renal cell carcinoma and that these deposits are located in the mesangial areas and not in the subepithelial space as it is often observed when glomerulonephritis is expressed by clinical symptoms.This work is supported by INSERM n^oCSSV, 78.5.206.5     

Cell heterogeneity in clear cell renal cell carcinoma

The aim of this study was to define the histological spectrum, frequency and significance of nonconventional tumour cells in clear cell renal cell carcinomas (CCRCC). Fifty‐one totally sampled CCRCC were studied histologically to evaluate the spectrum of cell morphology variability, its frequency and significance, and their correlation with tumour grade and stage, and other histological parameters of aggressive behaviour like necrosis. Aside from conventional clear/eosinophilic granular cells, three additional cellular types were identified and considered in this study: small clear cells, syncytial cells and rhabdoid cells. Small clear cells were detected in 11 cases (21.5%), syncytial cells in 8 (15.6%) and rhabdoid cells in 5 (9.8%). The presence of syncytial and rhabdoid cells statistically correlated with grade (p = 0.003 and p = 0.006) and stage (p = 0.049 and p = 0.05) in CCRCC. Necrosis correlated with stage (p = 0.018) and grade (p = 0.004), but not with syncytial, rhabdoid or small clear cells. The presence of syncytial and rhabdoid cells in CCRCC is a relatively frequent event that significantly correlates with high‐grade tumours and high stage status.     

Mucin-secreting clear cell renal cell carcinoma. A rare variant of conventional renal cell carcinoma

We report herein one case of conventional renal cell carcinoma (RCC) producing extensive extracellular mucinous secretion in a 71-year-old man. To the best of our knowledge, the presence of mucinous secretion in this tumor has not been documented. Mucin production, despite its low frequency, can be considered an additional feature of conventional RCC. Therefore, clear cell RCC should be added to the list of parenchymal renal tumors that can show significant mucin secretion; and it should be included in the inventory of morphologic variations of this tumor, which may cause diagnostic difficulties. It is of primary importance to distinguish mucin-secreting clear cell RCC from the metastasis of a mucin-secreting tumor to conventional RCC. Presence of mucin in a clear cell carcinoma does not exclude a renal origin.     

肾细胞癌相关标记物促红细胞生成素、CD10和肾细胞癌标记在弥漫性恶性间皮瘤和转移性肾细胞癌中的表达

转移性肾细胞癌（MRCC）与弥漫性恶性间皮瘤（DMM）一样可以引起胸腔积液、胸膜增厚和胸壁肿块，形态学上MRCC有时候与DMM无法区分。虽然有一些间皮相关抗体如CK5／6和calretinin可以区分DMM和MRCC，但这些抗体对DMM并不是完全特异性的，偶可表达于肾细胞癌。为了进一步区分DMM和MRCC，作者研究了145例DMM和20例MRCC中CD10和肾细胞癌标记（RCCMa）的表达，同时检测了100例DMM和20例MRCC中促红细胞生成素（EPO）的表达。结果发现EPO在所有的DMM和MRCC中表达，54％的DMMs和100％MRCCs表达CD10，RCCMa分别在26％DMMs和55％MRCCs中表达。     

A case of renal transitional cell carcinoma associated with synchronous contralateral renal cell carcinoma

We report a case of simultaneous contralateral renal transitional cell carcinoma and renal cell carcinoma. A 63-yr-old male presented with hematuria. He was diagnosed with left renal pelvis tumor and contralateral renal cell carcinoma. Subsequently, the patient received left nephrectomy and paraaortic lymphadenectomy (transitional cell carcinoma, pT3N2M0). Post-operatively, chemotherapy of renal pelvis tumor and angioinfarction of contralateral renal cell carcinoma are being considered. We believe that management planning should be individualized in such cases.