Malignant pilomatricoma. An immunohistochemical study with antihair keratin antibody.

A case is reported of malignant pilomatricoma confirmed by immunohistochemistry using anti-human hair keratin (anti-HHK) antibody prepared by the authors. The tumor occurred in the soft tissue of the inguinal region of an 88-year-old woman, with later invasion of the epidermis. No other possible primary lesion was found at autopsy. Histologically, the tumor was squamous cell carcinoma with nests of tumor cells and shadow cell-like necrotic cells showing central keratinization and focal calcification. Immunohistochemically, the hair keratin was positive in this tumor and in benign pilomatricomas exclusively. All other skin lesions and various squamous cell carcinomas examined were negative for this antigen. The staining patterns of commercial antiepidermal keratin and antiinvolucrin antibodies were significantly different from that of anti-HHK in normal skin and in these lesions. To the authors' knowledge, this is the first case of malignant pilomatricoma tested with anti-HHK staining. Malignant pilomatricoma is generally a low-grade malignant tumor, but it can metastasize and be fatal as it was in this case.     

Carcinogenic activity of endogenously synthesized N-nitrosobis(2-hydroxypropyl)amine in rats administered bis(2-hydroxypropyl)amine and sodium nitrite

The carcinogenic activity of endogenously synthesized N-nitrosobis(2-hydroxypropyl)amine(BHP) was investigated in male Wistar rats administered bis(2-hydroxypropyl)amine(BHPA) mixed in powder diet at a concentration of 1%, and sodiumnitrite (SN) dissolved in distilled water at concentrationsof 0.15 and 0.3%, for 94 weeks. Urinary excretion of BHP wasdetected in rats given 1% BHPA and 0.3% SN but not in the groupsreceiving either of these precursors alone. Nasal cavity, lung,esophagus, liver and urinary bladder tumors were found in animalstreated with combinations of 1% BHPA and 0.15 or 0.3% SN, suggestingthat the target organs of the endogenously synthesized BHP aresimilar to those affected when the carcinogen is administeredexogenously. The incidences of nasal cavity and lung tumorsreached 74 and 58% in rats given 1% BHPA and 0.3% SN, respectively.Tumors at sites other than target organs were only found atlevels similar to those previously reported for spontaneoustumors in male Wistars. The present results clearly indicatedthe tumor inducibility of a nhrosatable amine, BHA, throughan endogenous nitrosation by feeding to rats in conjunctionwith nitrite, and provide further suggestive evidence that endogenousnitrosations of environmental nitrosatable amines can be a potentialrisk factor in human cancer development.     

Histiocytic necrotizing lymphadenitis

Eleven cases of histiocytic necrotizing lymphadenitis were studied. Originally four were misdiagnosed as cervical tuberculous lymphadenitis. The characteristic symptoms and signs were local tenderness, fever, leucocytopenia and good prognosis. Antibody to Epstein-Barr virus was elevated in 2 of 3 cases. Biopsy of the affected lymph node was necessary when the differential diagnosis from lymph node tuberculosis or malignant lymphoma could not be made. The characteristic histological feature was focal necrosis without neutrophil infiltration in cortical or subcortical areas. Ultrastructurally, we found characteristic inclusions ('tubulo-reticular structures') in histiocytes and lymphocytes.     

Expression of the glutathione S-transferase placental form in human lung carcinomas

Expression of glutathione S-transferase placental form (GST-)in human lung carcinoma tissue taken at autopsy or biopsy wasinvestigated immunohistochemically. All of 34 cases of squamouscell carcinomas, including poorly, moderatelyand well-differentiatedexamples were shown to stain positively for GST-. Poorly differentiatedadenocarcinomas were, however, negatively stained (0/5 cases),while moderately and well differentiated adenocarcinomas werefound tostain with GST- at rates of 69% (9/13 cases) and 71%(5/7 cases), respectively. Six cases of small cell carcinomasexamined were all negative. The results indicate that GST- maybe a useful marker fornon-small cell type lung cancer, especiallysquamous cell carcinoma which is in agreement with findingsfor rat lung neoplastic lesions reported previously.     

Possible involvement of arachidonic acid metabolism in phenobarbital promotion of hepatocarcinogenesis

The effects of inhibitors of arachidonic acid metabolism andantioxidants on the rat liver tumor promotion activity of phenobarbital(PB) were assessed using the enzyme-altered focus as the end-pointlesion. Fischer 344 male rats were initiated with N-nitrosodiethylamine(200 mg/kg) and then divided into five groups placed on basaldiet, diet containing 0.05% PB, diet containing 0.05% PB plus0.75%, 1% or 1.5% levels of various inhibitors of arachidonicacid metabolism or antioxidants, or diet containing 1% or 1.5%inhibitors or antioxidants alone for 10 weeks, and then killed.-Bromo phenacyl bromide, an inhibitor of phospholipase A₂ significantly inhibited the promotion activity of PB at dose levelsof 0.75% and 1.5%, reaching plateau at 0.75%. Both quercetin,an inhibitor of lipoxygenase, and morin, a dual inhibitor oflipoxygenase-cyclooxygenase, significantly reduced the promotionactivity of PB at the 1.5% but not 0.75% dose levels. Moreover,acetylsalicylic acid, an inhibitor of cyclooxygenase dose-dependentlyinhibited the promotion activity of PB. Among the antioxidantsinvestigated, vitamin E did not affect, but n-propyl gallateand ethoxyquin exerted a dose-dependent inhibition of PB promotion.These results are strongly suggestive of an involvement of phospholipaseA₂ lipoxygenase and cyclooxygenase arachidonic acid metabolicpathways in the mechanisms underlying PB enhancement of hepatocarcinogenesis.     

Early lymphoma coexisting with reactive lymphoid hyperplasia of the stomach

A 55-year-old woman with a small focus of malignant lymphoma, 6 mm in diameter, arising within an area of reactive lymphoid hyperplasia (RLH) of the stomach is reported. The diagnosis of lymphoma was suspected by the preoperative endoscopic biopsy. This is the case of this association with an unusually small lymphoma in the early stage, in support of the view that there may be an intimate histogenetic relationship between lymphoma and RLH.     

Clonality analysis of different histological components in combined small cell and non-small cell carcinoma of the lung

Combined small cell and non-small cell carcinoma is relatively rare in the lung. Examination of the clonal relationship of different components in this type of tumor may give a clue to the rarity. We retrieved 6 such tumors; all 6 had small cell carcinoma and adenocarcinoma components, and 3 had an additional squamous cell carcinoma component. We examined the point mutations in the p53 gene and allelic loss (ie, the loss of heterozygosity [LOH] pattern) of chromosome 3p in each component. p53 mutations were detected in the small cell carcinoma component of 5 tumors and in the non-small cell carcinoma components of 2 tumors. In 1 case, the squamous cell carcinoma component had a p53 mutation locus identical to that in the small cell carcinoma component, but in the other case, the adenocarcinoma component had a different mutation than that in the small cell carcinoma component. Chromosome 3p LOH loci in the squamous cell carcinoma component were present in the small cell carcinoma component in all 3 cases, but some LOH loci were not identical in the small cell carcinoma and adenocarcinoma components in 3 cases. These results suggest that the small cell and squamous cell carcinoma components of combined small cell lung carcinomas have an intimate clonal relationship. On the other hand, the adenocarcinoma component often may be derived from a separate clone or, more likely, undergo a progressive process separate from the squamous cell-small cell carcinoma beginning in a very early stage, that is, before the appearance of p53 and chromosome 3p abnormalities. This tumorigenesis process may explain the relative rarity of combined small cell and non-small cell carcinoma, which occurs primarily in the peripheral lung, an infrequent site of squamous cell carcinoma.     

PNEUMATOSIS CYSTOIDES INTESTINALIS

Two cases of pneumatosis cystoides intestinalis (PCI), apparently of different etiologies, were found at autopsy in cancer patients. One case was associated with chronic obstructive lung disease and with emphysema of soft tissues of the mediastinum, retroperitoneum, and mesentery, whereas the other showed pseudomembranous enteritis with bacterial and fungal overgrowths. The latter case supports the role of gas-forming bacteria, while the former provides an anatomical evidence of pulmonary disease as a cause of PGI. Obstruction of the upper gastrointestinal tract may contribute to the occurrence of PGI by a complication of aspiration pneumonitis or disturbance of the normal bacterial flora of the intestine as well as an increase of the intraluminal pressure. In addition to the etiologic considerations, the importance of clinical diagnosis of PGI has been emphasized since both cases in the present report were more or less related to the cause of death.     

Thymic sarcomatoid carcinoma with skeletal muscle differentiation: report of two cases, one with cytogenetic analysis

AIMS: Malignant thymic tumour histologically resembling a soft tissue sarcoma is extremely rare and defined as sarcomatoid carcinoma in the recent World Health Organization (WHO) classification. We report two such cases in which the tumour cells showed a prominent rhabdomyoblastic differentiation and analyse whether these tumours retain an epithelial nature at least in part. METHODS AND RESULTS: One tumour occurred in a 51-year-old man (Case 1) and the other in a 40-year-old woman (Case 2). Microscopically, both tumours consisted essentially of two types of tumour cells: spindle and large round cells, with no apparent epithelial components. Osteosarcomatous small foci were also found in Case 2. Immunohistochemically, desmin and muscle-specific actin were positive in the majority of both types of tumour cells, whereas myogenin was predominant in the spindle cells and myoglobin in the large round cells. Some of both types of cells expressed cytokeratin with co-expression of myoglobin in the large round cells, but with no myogenin in the spindle cells. Some cytokeratin-positive spindle cells were also negative for desmin. Ultrastructural examination of a recurrent tumour in Case 2 revealed some epithelial features among the spindle cells. Cytogenetic study of the same tumour showed a complex abnormality including der(16)t(1;16)(q12;q12.1), an identical pattern previously reported in a case of thymic squamous cell carcinoma. CONCLUSIONS: The findings support the definition in the WHO classification of sarcomatoid carcinoma that includes purely sarcomatous tumour as in the present cases. Occurrence of this type of tumour may indicate a relationship between thymic epithelial cells and myoid cells and/or a potential for divergent differentiation in thymic epithelial tumours.     

Membrane attack complex of complement and 20 kDa homologous restriction factor (CD59) in myocardial infarction

In order to investigate the mechanism of deposition of the complement membrane attack complex (MAC) in cardiomyocytes in areas of human myocardial infarction, the 20 kDA homologous restriction factor of complement (HRF20; CD59) and complement components (C1q, C3d and MAC) were analysed immunohistochemically using specific antibodies. Myocardial tissues obtained at autopsy from nine patients who died of acute myocardial infarction were fixed in acetone and embedded in paraffin. The ages of the infarcts ranged from about 3.5 h to 12 days. In cases of myocardial infarction of 20 h or less, MAC deposition was shown in the infarcted cardiomyocytes without loss of HRF20. Where the duration was 4 days or more, the cardiomyocytes with MAC deposition in the infarcted areas also showed complete loss of HRF20. Outside the infarcts, HRF20 in the cardiomyocytes was well preserved without MAC deposition. The present study suggests that the initial MAC deposition in dead cardiomyocytes can occur as a result of degradation of plasma-membrane by a mechanism independent of complement-mediated injury to the membrane. Loss of HRF20 from dead cardiomyocytes may not be the initial cause of MAC deposition, but may accelerate the deposition process of MAC in later stages of infarction.