PRR11 immunoreactivity is a weak prognostic factor in non-mucinous invasive adenocarcinoma of the lung.

INTRODUCTION: Proline-rich protein 11 (PRR11) functions in the progression of cell cycle, and silencing the PRR11 gene in lung cancer cells results in the inhibition of cellular proliferation, cell cycle progression, cell migration, invasion and colony formation. PRR11 may therefore be a therapeutic target in lung cancer. MATERIALS AND METHODS: Microarrays of surgical specimens of non-mucinous invasive adenocarcinoma of the lung, from 346 subjects that were not given preoperative therapy, were autoimmunostained with PRR11 and, except for trace and pseudo-positivity, assessed as "positive" at any proportion and intensity. RESULTS: PRR11 immunoreactivity demonstrated a tendency to associate with an aggressive phenotype (tumor size, vascular invasion, and adjuvant therapy) and some effect on overall survival (Hazard ratio 1.51). CONCLUSIONS: PRR11 may be a weak prognostic indicator of overall survival of patients with non-mucinous invasive adenocarcinoma of the lung.

Coexistence of brenner tumor and struma ovarii: case report.

BACKGROUND: There has been controversy regarding the histogenesis of Brenner tumors. It is generally accepted that Brenner tumors are derived directly from ovarian surface epithelium, which undergoes metaplasia to form the typical urothelial-like components, whereas some investigators assume that Brenner tumors arise from immature germ cells. CASE: We describe a well-documented case of the coexistence of struma ovarii regarded as a form of teratoma and Brenner tumor in the same ovary. Immunohistologically, not only columnar cells of thyroid follicles, but also transitional cells of Brenner nests were positive for thyroglobulin. CONCLUSIONS: In the present case, Brenner tumors and thyroid elements coexisted and were positive for thyroglobulin. While there is strong evidence that pure Brenner tumors originate mostly from the ovarian surface, at least Brenner tumors associated with teratomatous elements may have a germ cell origin.

Epithelioid trophoblastic tumor (ETT) initially interpreted as cervical cancer.

The epithelioid trophoblastic tumor (ETT) is a rare form of trophoblastic disease and shows a wide spectrum of differential diagnoses and clinical behavior. A 53-year-old woman presented with ETT presumably originated in spontaneous delivery of 25 years ago and was initially diagnosed as cervical cancer on cervical punch biopsy followed by radical hysterectomy. The uterus showed a small tumor restricted to the cavum with no cervical infiltration, resembling ETT in histologic and immunohistochemical features. The difficulties and clues in distinguishing ETT from nontrophoblastic lesions are discussed.

Refraction imaging and histologic correlation in excised tissue from a normal human lung: preliminary report.

RATIONALE AND OBJECTIVES: The authors performed this study to evaluate the spatial resolution of refraction imaging performed with synchrotron radiation (SR) on 2-mm-thick sections of excised normal human lung. MATERIALS AND METHODS: Refraction images of specimens from a normal human lung were obtained with 19 keV, a 5-second exposure time, and a 2.4 x 2.4-cm field of view. The specimen-detector distance was 83 cm. RESULTS: Structures of secondary pulmonary lobule consisting of pulmonary arteriole, terminal bronchiole, air sac, and venules in the interlobular septum in normal lung were clearly illustrated on refraction images obtained with SR. The imaging findings showed good correlation with those from histologic examination. The spatial resolution of the refraction images was approximately 10-30 microm, as measured with light microscopic analysis of specimens stained with hematoxylin-eosin. CONCLUSION: With refinement, this technique may have some practical purpose for diagnosing lung disease in vivo.

Various scoring systems evaluating histologic features of chronic hepatitis C treated with interferon.

Various scoring systems for chronic hepatitis have been proposed; however, there is no standard scoring system for studies of interferon (IFN) therapy in patients with chronic hepatitis C. The aims of this study were to determine the most useful system reflecting histologic changes in biopsy specimens from complete responders and predicting the efficacy of IFN therapy. Patients with chronic hepatitis C were administered IFN-alpha for 6 months. Forty-six patients were included in this study and categorized as complete responders (n = 15), partial responders (n = 24), and nonresponders (n = 7) according to viral and biochemical responses to the therapy. Biopsy specimens obtained from each patient before and after treatment were evaluated under 3 different systems: Histological Activity Index (HAI), modified HAI, and Scheuer classification. Complete responders showed considerable improvement in both grade and stage on the modified HAI and Scheuer classifications. On the HAI, a considerable improvement was observed in grade but not in stage. No significant change was observed in partial responders or nonresponders on any system. Prediction of complete response was not possible under any system, but the pretreatment score reflecting piecemeal necrosis on any 1 of the 3 classifications and the fibrosis score on Scheuer classification were predictors of nonresponse. The modified HAI system and Scheuer classification were amply useful in evaluating histologic changes in complete responders. Scores higher than 4 of the categories reflecting piecemeal necrosis on any system and fibrosis scores of 3 or 4 on Scheuer classification predicted nonresponse to IFN therapy.

Pathogenesis of multifocal micronodular pneumocyte hyperplasia and lymphangioleiomyomatosis in tuberous sclerosis and association with tuberous sclerosis genes TSC1 and TSC2.

Tuberous sclerosis (TSC) is a rare, genetically determined disorder / familial tumor syndrome, currently diagnosed using specific clinical criteria proposed by Gomez, including the presence of multiorgan hamartomas. Pulmonary involvement in TSC is well known as pulmonary lymphangioleiomyomatosis (LAM), which has an incidence of 1-2.3% in TSC patients. LAM has immunohistochemical expression of both smooth-muscle actin and a monoclonal antibody specific for human melanoma, HMB-45. It has recently been reported that multifocal micronodular pneumocyte hyperplasia (MMPH) associated with TSC should be considered as a distinct type of lung lesion, whether it occurs with or without LAM. Two predisposing genes have been found in families affected by TSC; approximately half of the families show linkage to TSC1 at 9q34.3, and the other half show linkage to TSC2 at 16p13.3. TSC genes are considered to be tumor suppressor genes, and mutations in them may lead to abnormal differentiation and proliferation of cells. Tuberin, the TSC2 gene product, has recently been found to be expressed in LAM and MMPH. In this article we discuss the histogenesis and genetic abnormalities of neoplastic lesions associated with TSC, and we review the current understanding of the pathogenesis of pulmonary hamartomatous lesions such as LAM and MMPH in TSC.

Autopsy case of alcoholic hepatitis and cirrhosis treated with corticosteroids and affected by Pneumocystis carinii and cytomegalovirus pneumonia.

A case of the very early phase of Pneumocystis carinii pneumonia in a human immunodeficiency virus (HIV)-negative man with alcoholic hepatitis and cirrhosis treated with steroids is presented. A 40-year-old man with a 10-year history of alcohol abuse was admitted to hospital with jaundice, fever and macrohematuria. Laboratory examinations revealed neutrophilic leukocytosis and a serum bilirubin level of 13.9 mg/dL. The serum bilirubin level rose to 28.5 mg/dL over 1 month. Prednisolone administered orally for 10 days produced a slight improvement in the jaundice and fever. After an interval of a week, it was resumed and maintained for 22 days (total dose, 1555 mg) until the patient died of a massive hemorrhage from ruptured vessels of a gastric ulcer. An autopsy disclosed P. carinii pneumonia in the lower lobe of the left lung, cytomegalovirus infection in both lungs and the esophagus, and esophageal candidiasis. To our knowledge, this is the first report of P. carinii pneumonia together with cytomegalovirus infection in an HIV-negative alcoholic patient. The present case suggests that a rare opportunistic infection such as P. carinii pneumonia might be caused by treating cirrhosis and alcoholic hepatitis with corticosteroids, even if only for a relatively short period.

Subcutaneous malignant epithelioid schwannoma with cartilaginous differentiation.

BACKGROUND: Malignant epithelioid schwannoma is a rare tumor. The aim of this study is to describe a case of subcutaneous malignant epithelioid schwannoma with cartilaginous differentiation. METHODS: Histological, immunohistochemical, and ultrastructural examinations were performed on a tumor that arose on the back of a 37-year-old woman. RESULTS: Histologically, the tumor predominantly consisted of small, round or polygonal cells arranged in cords or nests. Immunohistochemical study revealed that the tumors cells were positive for vimentin, S-100 protein, glial fibrillary acidic protein and neuron specific enolase. The cells were negative for HMB-45, keratin, epithelial membrane antigen, and CAM5.2. Electron microscopic study showed closely associated cells with undifferentiated features. The cells were devoid of external laminae and cellular junctions. CONCLUSION: Malignant epithelioid schwannoma should be pathologically differentiated from other epithelioid tumors with cartilaginous elements.

Pigmented neurofibroma: report of two cases and literature review.

Two cases of pigmented neurofibroma of the skin are reported. In case 1, the tumor was removed from the back of a 55-year-old man with no associated neurofibromatosis. In case 2, the tumor was removed from the abdominal wall of a 21-year-old woman with neurofibromatosis. Both tumors consisted of benign, short spindle cells and multiple foci of scattered melanin-laden cells. In case 1, the spindle cells were arranged in a storiform pattern, resembling features of dermatofibrosarcoma protuberans. Immunohistochemically, the spindle cells of both cases were demonstrated to be positive for S-100 protein and CD34. The melanin-laden cells stained positively for HMB-45. This report describes an additional two cases of pigmented neurofibroma that conform to the new diagnostic criteria for this disease.

Interstitial pneumonia in Hermansky-Pudlak syndrome: significance of florid foamy swelling/degeneration (giant lamellar body degeneration) of type-2 pneumocytes.

Although usual interstitial pneumonia (UIP)-like IP has been known as the most serious complication of Hermansky-Pudlak syndrome (HPS), its pathologic features and pathogenesis are poorly understood. We investigated biopsied and autopsied lung tissues from five patients who died of UIP-like IP associated with HPS (HPSIP). The salient histopathologic features of HPSIP observed were: (1) alveolar septa displaying florid proliferation of type-2 pneumocytes (2PCs) with characteristic foamy swelling/degeneration; (2) patchy fibrosis with lymphocytic and histiocytic infiltration centered around respiratory bronchioles, occasionally showing constrictive bronchiolitis; and (3) honeycomb change without predilection for the lower lobes or subpleural area. Those peculiar 2PCs were histochemically characterized by the over accumulation of phospholipid, immunohistochemically by a weak positivity for surfactant protein, and ultrastructurally by the presence of numerous giant lamellar bodies that compressed the nucleus with occasional cytoplasmic disruption, together suggesting a form of cellular degeneration with an over accumulation of surfactant (giant lamellar body degeneration). The present study strongly indicates that there is a basic defect in the formation/secretion process of surfactant by the 2PCs in HPS, which may well be the triggering factor for the HPSIP development. Other factors, such as macrophage dysfunction, may be working synergistically for further acceleration of the inflammatory process.

[Pulmonary adenocarcinoma with central ossification].

A 70-year-old woman was admitted in April 1997 because a coin lesion in the left middle lung field was observed on chest roentgenograms. The lesion had slightly increased in size since 1994, when it was first pointed out. Chest computed tomography elucidated a high density area with irregular borders in the center of the shadow in S 3 a. Transbronchial biopsy revealed adenocarcinoma, and a left upper lobectomy was performed. The resected specimen demonstrated a tumor with central ossification and pleural indentation. Histologic examination determined that the the tumor was a papillary adenocarcinoma with central ossification containing marrow tissue. Primary lung cancer with central ossification is very rare, and only 6 cases have been reported to date, including this case.

Benign schwannoma of the esophagus removed by enucleation: report of a case.

A submucosal tumor of the esophagus was enucleated by a thoracotomy. A microscopic examination showed the tumor to be composed of spindle-shaped cells showing mild nuclear atypia with vague nuclear palisading and scarce mitotic figures. The tumor was surrounded by peripheral lymphoid cuffs. An immunohistochemical study demonstrated diffuse positive staining for S-100 protein in the tumor cells. The lesion was diagnosed to be an esophageal schwannoma based on these pathological features. Benign schwannoma of the esophagus has been described in five cases in four reports in the English literature. This is the sixth case diagnosed by immunohistochemical studies.

Stromal Leydig cell tumor of the ovary. Case report and literature review.

The stromal Leydig cell tumor is a very rare benign tumor originating from the ovarian stroma. Only seven cases have been reported, all in postmenopausal women, except for one in a 15-year-old girl. In the present case, masculinization developed over a few months in a 24-year-old woman. The serum concentration of testosterone was 4.7 ng/ml before operation. Left salpingo-oophorectomy and wedge resection of the right ovary were performed. The encapsulated left ovarian tumor was an ovarian stromal Leydig cell tumor on microscopic examination.

[Undiagnosed lung cancer complicated by intracavitary aspergillosis].

A 54-year-old man was treated with an antifungal agent (itraconazole) for post-tuberculous intracavitary aspergillosis. Though clinical and radiological findings indicated that the patient's symptoms had gone into remission, aspergillosis recurred 4 months after the cessation of antifungal chemotherapy, requiring that the patient undergo an operation. Intraoperative and pathological findings revealed a squamous cell carcinoma contiguous to the cavity containing the aspergilloma. Though a few cases of aspergilloma within cavitating pulmonary carcinomas have been reported in the literature, the case of lung cancer we report was thought to arise from preformed lung scars surrounding a post-tuberculous cavity that contained an aspergilloma. Although conclusive distinctions between neoplasms and fungal infections are difficult to make, careful observation of the radiographic features is necessary when treating patients with fungus ball-type aspergillosis.

Colonic obstruction induced by plasma cell granuloma of the transverse colon: report of a case.

Plasma cell granuloma is mainly composed of reactive plasma cell proliferation, the origin of which is uncertain. Immunohistochemically, the plasma cells are characterized by a polyclonal nature, and must be distinguished from plasmacytoma which displays a monoclonal nature. This tumor is most commonly found in the lung and bronchus, but has rarely been described in the alimentary tract. We report herein a case of plasma cell granuloma of the transverse colon. A 71-year-old woman was admitted for lower abdominal pain with severe inflammation and anemia. Ultrasound examination and computed tomography showed an abdominal tumor. Barium enema revealed the tumor to be located in the transverse colon causing colonic obstruction. The resected tumor was spherical and mainly spread in the submucosal layer. Microscopically, the tumor consisted of severe infiltration of mature plasma cells within the spindle-shaped myofibroblasts. Immunohistochemical studies showed IgA, IgG, IgM, and kappa and lambda chains, and revealed a polyclonal nature of the plasma cells. Thus, a pathological diagnosis of plasma cell granuloma affecting the transverse colon was made. To the best of our knowledge, this is the first report of successful surgical resection of plasma cell granuloma of the colon.

[A case of syringomatous carcinoma derived from the lid].

A 73-year-old male presented with a slowly growing tumor in the right lower eyelid of one year's duration. The condition had been diagnosed elsewhere as poorly differentiated squamous cell carcinoma by biopsy. The residual tumor progressed rapidly and metastatized to the ipsilateral preauricular lymph nodes. We performed orbital evisceration and radical neck resection. Microscopically, the tumor showed small epithelial nests, cords, and ductal structure buried in abundant collagenous stroma. Besides focal squamous differentiation with keratinization in the surface area, the tumor showed, as cardinal features, ductal differentiation possessing comma-like extensions identical to syringoma. Cellular atypia, invasive growth pattern, and remarkable perineural invasion were suggestive of malignancy. These features led to the diagnosis of syringomatous carcinoma. Immunohistologically, the tumor showed positive staining for cytokeratine and epithelial membrane antigen (EMA). It was mostly negative for S-100 and carcinoembryonic antigen (CEA).

Eccrine adenocarcinoma of the lacrimal sac region.

Eccrine adenocarcinoma of the lacrimal sac region is described in a 48-year-old man. The case was first diagnosed as an adenocarcinoma and removed by dacryocystectomy, but unfortunately the neoplasm recurred after a period of 1 year. Examinations with periodic acid-Schiff (PAS) and several antibodies indicate that this is a hitherto undescribed eccrine adenocarcinoma, and finally the case was managed by orbital exenteration. This is the first case of eccrine adenocarcinoma of the lacrimal sac region to be documented in the world literature.

Airway lesions and superoxide dismutase (SOD) distribution in bronchopulmonary dysplasia (BPD).

We examined 71 cases of bronchopulmonary dysplasia (BPD) at autopsy and divided them into five groups on the basis of the patients' survival time, studying on the histological changes in the airways for the purpose of clarifying the pathogenesis of BPD from hyaline membrane disease (HMD). Furthermore, bronchiolar occlusion was classified into four types: secretion, obliterative bronchiolitis, intraluminal plug, and hyperplasia of bronchiolar components. The same occlusive findings as in bronchioli and hyaline membrane were observed from respiratory bronchioles to alveolar ducts. However, there was no obvious correlation between airway lesions and accompanying alveolar lesions excepts three cases of obliterative bronchiolitis. Furthermore, immunohistochemical studies with anti-human SOD antibodies were performed. Mn-SOD was positive for alveolar macrophages in longer surviving infants without significant correlation with histological variation, whereas slightly positive or negative in infants who died within 1 week; CuZn-SOD was rarely positive in any cases. These results is highly correlated to the pathogenesis of BPD and to its pathological advancement with its clinical course.

Two cases of small cell carcinoma of the prostate.

We describe the clinical and pathological findings in two Japanese men with small cell carcinoma of the prostate; case 1 was 58 years old and case 2 was 24 years old. Case 1 was initially diagnosed as a poorly differentiated adenocarcinoma of the prostate, stage D2, with marked elevation of serum neuron-specific enolase (NSE), carcinoembryonic antigen (CEA), and CA 19-9 levels. The patient had undergone castration and systemic chemotherapy. After three courses of chemotherapy, tumour markers were normalized. However, 6 months later serum levels of tumour markers again rose, and biopsy of the prostate revealed a small cell carcinoma component in the adenocarcinoma of the prostate and benign prostate hypertrophy. The patient was again treated with systemic chemotherapy but died within 1 year after relapse. In case 2, the patient presented with initial symptoms of lumbago and dysuria, and an enlarged prostate was radiologically diagnosed. Shortly after admission he developed ileus, and an exploratory laparotomy revealed a large tumour arising from the prostate and invading the peritoneal cavity. This tumour was pathologically diagnosed as a small cell carcinoma. The patient died shortly thereafter without responding to chemotherapy. Immunohistological evaluation was done using a panel of antibodies against NSE, chromogranin A, CEA, CA 19-9, prostatic acid phosphatase (PAP), prostate-specific antigen (PSA), leukocyte common antigen (LCA), epithelial membrane antigen (EMA), adrenocorticotropic hormone (ACTH), calcitonin, serotonin, gastrin, vasoactive intestinal peptide (VIP), and glucagon. CEA was intensely positive in the tumour lesions from case 1, and NSE and ACTH were focally positive, and calcitonin, serotonin, CA 19-9, and PSA were weakly positive only in several cells in the tumour lesions from case 1. In the tumour lesion from case 2, NSE was intensely positive, and chromogranin A was weakly positive. These findings support the neuroendocrine nature of this neoplasm.