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Biomedical subjects

W Wöckel

Publications and source records attributed to W Wöckel.

At least 19 recordsLinked to original sources

The 17-1A antigen is expressed on primary, metastatic and disseminated non-small cell lung carcinoma cells.

In view of the high incidence of early distant tumor relapses in apparently completely resected (R0, M0) non-small cell lung cancer (NSCLC), there is a need for an adjuvant therapy. Considering the low tumor burden in these patients, an adjuvant therapy with monoclonal antibodies (i.e., the 17-1A MAb) might be appropriate. The purpose of our study was to test whether the 17-1A antigen is expressed on primary and metastatic NSCLC carcinoma cells. Using immunohistochemistry, the expression of 17-1A was analysed in primary tumors (n = 60) and in lymph node metastases (n = 7) of patients with NSCLC. Additionally, we investigated in 6 patients the expression of 17-1A on disseminated tumor cells in the bone marrow, which were detected by the pan-cytokeratin MAb A45-B/B3 using a double-labeling technique. The 17-1A antigen was homogeneously expressed in 47 (78.3%) out of 60 primary NSCLCs. The expression of 17-1A was independent from the tumor histology, the grade of differentiation, and other clinicopathological parameters (ploidy status, TNM-stage). Lymph node metastases were positive in 4 (57.4%) out of 7 cases. The double-labeling experiments demonstrated that 17-1A is coexpressed on disseminated tumor cells in the bone marrow in 5 (83%) out of 6 patients. The 17-1A antigen is expressed on the majority of primary, metastatic, and disseminated NSCLC cells. Patients with 17-1A-positive tumors might benefit from an adjuvant therapy with MAb 17-1A after completely resected NSCLC.

Antigens, Neoplasm↗

Overexpression of matrix metalloproteinase 2 predicts unfavorable outcome in early-stage non-small cell lung cancer.

This prospective study was performed to assess the impact of matrix metalloproteinase (MMP) 2 expression on the clinical course of patients with operable non-small cell lung cancer (NSCLC). Specimens of 193 consecutive patients with completely resected NSCLC were examined for MMP-2 expression by immunohistochemical staining with a polyclonal antibody. Homogeneous immunostaining of cancer cells was considered positive and heterogeneous, or no staining was considered negative concerning overexpression of MMP-2. Four specimens were excluded from further analyses because of unspecific staining. The median follow-up period was 71.5 months (range, 12-120 months). Overexpression of MMP-2 was observed in 64 (33.9%) of 189 patients and did not correlate with clinicopathoiogical parameters. In patients without lymph node involvement (pN0 stage) MMP-2 overexpression was an independent prognostic parameter for unfavorable outcome: Log-rank analysis showed a significant association of MMP-2 overexpression with shortened cancer-related survival (P = 0.04) and disease-free survival (P = 0.03). Multivariate regression analysis confirmed MMP-2 overexpression as predictor of shortened cancer-related survival in NSCLC without lymph node involvement (P = 0.005, relative risk, 2.6). The present study revealed that MMP-2 overexpression predicts a poor prognosis in early-stage NSCLC. Therefore, it might be worth investigating the role of MMP inhibitors as adjuvant therapeutic agents in NSCLC.

Adult↗

[Polyvinylpyrrolidone deposits in the pleura].

We report on the case of a 45-years old woman with repeated pleural effusions lasting for 2 years. She had a history of breast carcinoma 6 years ago, which was treated by breast amputation and radiation. After repeated histological and cytological examinations no tumorous compromise of the pleura or other cause for the effusions could be found. A pleural resection was performed. On the histological and electron microscopical examination deposits of a foreign substance were found, which was identified as polyvinylpyrrolidone. This substance was obviously introduced in the pleural cavity by the attempts to treat the effusions by pleurodesis with Diclofenac and Tetracycline (Vibravenös). The diagnosis is suggested by the histological findings, but it must be confirmed by anamnesis, also for PVP deposits in other organs.

Breast Neoplasms↗

A high frequency of tumors with rearrangements of genes of the HMGI(Y) family in a series of 191 pulmonary chondroid hamartomas.

Pulmonary chondroid hamartomas (PCHs) are benign mesenchymal tumors that often are characterized by specific chromosomal aberrations. Herein we report our cytogenetic and molecular cytogenetic (FISH) studies on 191 PCHs, including 48 previously published cases. In this series, 134/191 PCHs (70.2%) showed either abnormalities of chromosomal bands 6p21 (21 tumors), 12q14-15 (95 tumors), or had other abnormalities (18 tumors). Two tumors had a 6p21 aberration together with a 12q14-15 aberration. The most frequent translocations were t(12;14)(q15;q24) (19 cases) and t(6;14)(p21. 3;q24) (18 cases), both in either simple or complex form. By FISH with cosmids spanning the gene encoding the high-mobility-group protein HMGIC, we were able to show a rearrangement within or close to HMGIC in all tumors with 12q14-15 abnormalities tested, in 11 tumors with an apparently normal karyotype, and in 4 tumors with complex abnormalities without cytogenetically visible alterations of chromosomes 12. Rearrangements of HMGIY or its immediate surroundings were shown for 21 cases with 6p21 aberrations and three cases with other chromosomal abnormalities but without cytogenetically visible alterations of chromosomes 6. Genes Chromosomes Cancer 26:125-133, 1999.

Adolescent↗

[Primary bronchial malignant melanoma].

A 53-year-old man presented a melanotic lung tumor which was based in the bronchus of the left lower lobe and closed the left main bronchus. After laser therapy, left lobectomy with sleeve resection was carried out. Complications after the surgery required resection of the rest of the left lung and thoracoplasty. Based on the histological and immunohistochemical findings, the tumor was classified as a malignant melanoma. There was no past history of an excision or a fulguration of a cutaneous, mucous membrane, or ocular lesion. Examination of the skin and the eyes did not yield any evidence of another primary tumor. We conclude that the lesion represents a primary malignant melanoma of the respiratory tract, a rare neoplasm of which only 21 cases have been confirmed. The patient does not have any evidence of tumor in the relatively short follow-up period of 10 months.

Biomarkers, Tumor↗

[Lymphoepithelioma-like lung carcinomas].

Having observed 2 cases of lymphoepithelioma-like carcinoma of the lung in a 49-year-old female and in a 66-year-old male patient, we present a review on this entity, which was described for the first time in 1987. Essentially this neoplasm has the same histological appearance as a Schmincke-Regaud tumor, but it is possible that a certain morphological variety exists. In the differential diagnosis, a metastasis of a Schmincke-Regaud tumor and a malignant lymphoma should be considered. Including our 2 cases, a total of 30 cases have been reported: 14 male patients aged between 33 and 73 years and 12 female patients between 38 and 70 years; in 4 cases there was no reference to sex or age. Most of the patients were Asians, mainly Chinese. These tumors presented with nearly the same frequency in both lungs. They mostly appeared as peripheral coin lesions in the chest X-ray study. Lymph node metastases were found in approximately 25% of the cases. Hematogenous metastases seldom occurred and were observed almost only in the skeletal system. In most cases a lobectomy was performed. At present, no exact assertion is possible regarding the prognosis. An association with an Epstein-Barr virus infection was observed in the Asian patients, but not in the Caucasian patients.

Adult↗

[Atypical morphologic lung manifestations of Pneumocystis carinii infection in AIDS patients].

We report on unusual presentation forms of Pneumocystis carinii infection of the lung in two patients with AIDS. A 36-years-old woman presented a cavitation in the lung middle lobe and bullous changes in the apical portion of the right upper lobe on the chest x-ray. The biopsy of these lesions was not diagnostic and the patient was operated on. The surgical specimen of the removed lung segment showed a cavitary lesion with a border of granulation tissue with giant cells, focal recent and older hemorrhages, rests of fibrinous exudate and dystrophic calcifications. In the surrounding tissue there were Pneumocystis carinii in the alveolar spaces and also in the alveolar walls, this tissue invasion through the organisms being most probably the cause of the cavitary change. A cytomegalic virus infection was also found. A 30-years-old man presented patchy pulmonary infiltrates on his x-ray. The examination of bronchial secretion and bronchial washing specimens revealed P. carinii. In addition, the organisms were demonstrated in the walls of pulmonary vessels and in the stroma of the bronchial mucosa on the biopsy. In a sample of lung tissue which was taken after death, there were no Pneumocystis carinii anymore, but some proliferations of connective tissue with giant cells and calcification, which could represent residual changes of the Pneumocysts carinii infection. Besides, persisting changes of cytomegaly were found. We conclude that a Pneumocystis carinii infection should be considered in all HIV-positive or AIDS patients with any kind of lung lesions.

AIDS-Related Opportunistic Infections↗

[Regeneration of bronchial mucosa after short-term repetition of biopsy versus bronchial carcinoma].

We report on two patients, 74 and 73 years old, each of whom had had biopsy of the bronchial mucosa elsewhere. Histologically, normal mucosa and mild bronchitis was seen, respectively. In both patients a second biopsy specimen from the same site was taken, 4 and 7 days after the first biopsy. Now the diagnosis was carcinoma in situ (not excluding early squamous carcinoma) and squamous carcinoma, respectively. One of the patients came to our lung clinic for operation on the basis of the mentioned diagnosis. A third biopsy was performed for control purposes. It revealed just a perforation of a lymph node in the bronchial wall and some epithelioid granulomas without evidence of acid-fast bacilli. There was no evidence of malignancy in this specimen. Because of the discrepancy, the pathologist at the first institution was asked to send us the previous slides. On review of these slides, the described findings were seen, but they were interpreted as regenerative-atypical. In this way, an unnecessary surgical intervention was avoided. After a follow-up of 3 1/2 years the patient is healthy. In the other patient, because of the diagnosis of squamous carcinoma a lobectomy was undertaken by a surgeon elsewhere. The pathologist could not find any carcinoma in the surgical specimen. The biopsy material was reviewed in our department, the findings being interpreted as atypical, originating in reparative changes. Like the postoperative pathologist, we did not find any carcinoma in the surgical specimen. In both cases, therefore, regenerative-atypical changes after re-biopsy were first misinterpreted as a malignant process.

Aged↗

Native pulmonary muscular proliferation.

Four cases with native pulmonary muscular proliferation (NPMP) are reported. The etiology of this rare condition is unknown. A hamartomatous process is discussed. In spite of its rarity the correct diagnosis of this condition is important. Both clinically and histologically in transbronchial biopsies, NPMP may be mistaken for pulmonary lymphangioleiomyomatosis (PLAM). Distinction of these 2 conditions is adamant, as PLAM has a poor prognosis, and, moreover may be associated with general disease, as with tuberous sclerosis. Whereas the typical distribution of more mature desmin positive muscle cells in a dense center core and more immature desmin negative radiating peripheral muscle cell proliferation with fascicular pattern in NPMP may be recognized in open lung biopsy, these differences may not become evident in small transbronchial biopsies. Immunohistochemical methods play an important role in the differential diagnosis--as with PLAM estrogen and progesterone receptors may be expressed and, most importantly, the reaction of the HMB45-antibody appears consistently positive in muscle cells of PLAM, while negative with NPMP. Thus, recognition of this clinically innocent disease is also possible in small tissue particles.

Actins↗

[Anticytoplasmic antibodies (cANCA) in syphilitic nodules of the lung].

HISTORY AND CLINICAL FINDINGS: A chest radiograph was done in a 75-year-old man with cough productive of a whitish sputum. It showed round foci in the right middle and upper lobes. Serum anticytoplasmic antibody (cANCA) was 1 : 160, suggesting Wegener's granulomatosis. But the pulmonary foci actually increased in size on administration of prednisolone, 10 mg daily. INVESTIGATIONS: As the lung biopsy was not diagnostic, a diagnostic thoracotomy with biopsy was done and the anterior segment of the right middle lobe resected. Histological examination revealed a gumma. Active syphilis was confirmed by a TPHA-Test with a titre of 1 : 40960. TREATMENT AND COURSE: Antisyphilitic treatment was given for 35 days, at first 1 mega (Penicillin E daily for five days, then erythromycin, 1000 mg, for five days, a penicillin rash having occurred. Serial serology showed a continual fall of the lues and cANCA titres. Four months postoperatively the titre in the TPHA test had fallen to 1 : 640, and was nonreactive after five years. cANCA titre fell to 1 : 16 and was negative 42 weeks after resection. CONCLUSION: The connection between pulmonary gumma and the presence of antiplasmatic antibodies remains unclear. Inflammatory changes in the vascular wall, which occur in both Wegener's granulomatosis and tertiary syphilis, may have played a role.

Aged↗

Melanotic paraganglioma of the posterior mediastinum.

A melanotic paraganglioma occurred in a 57-year-old woman, located in the left paravertebral space of the upper mediastinum. It was totally resected. During a 5 year follow up period neither tumour recurrence nor metastasis were observed. Histological examination of the tumour revealed a paraganglioma with monomorphous chief cell like elements which were arranged in a "zellballen" pattern. Immunohistochemical results also were in accordance with the diagnosis since neuron-specific enolase, chromogranin and synaptophysin were found in tumour cells whereas keratin was not. Additionally, neurosecretory granules were found in tumour cells during electron microscopy. A peculiar feature of the tumour was its strong pigmentation due to melanin located within the tumour cells and tumour associated melanophages. The simultaneous expression of functional properties of two different neural crest derived cells in one tumour stresses the close relationship between all neural crest elements and is in accordance with the observation of other melanotic, non-melanomatous tumours.

Cytoplasmic Granules↗

[Adenomatoid cystic lung abnormality in adults with associated bronchioloalveolar carcinoma].

Lung cysts were observed by chance in the chest radiographs from two women aged 20 and 41. In the surgical specimens the lesions proved to be congenital cystic adenomatoid malformation type 1. The cysts were partially lined by mucous cells. Also near the cysts there were circumscribed tubuloacinar proliferations of mucous cells. In both cases a transition into a bronchioloalveolar carcinoma was seen. Histochemically no sulphomucins could be demonstrated by means of an alcian blue pH 1 reaction in the tumor cells, but was demonstrated in the non-neoplastic cells of the malformation. In both cases CEA was demonstrated in the tumor cells. Some cells in the tubuloacinar proliferations were weakly CEA positive. In one patient the diagnosis of carcinoma was made by intraoperative frozen section and a lobectomy was performed. The other patient had first only a resection of her cystic lesions and had to be reoperated because of the results of the pathological examination. Both patients had no recurrence in the 8 years following the operation. In the literature we found 5 cases of congenital cystic adenomatoid malformation in adults. In 2 cases there was also an associated bronchioloalveolar carcinoma. Several reports exist on the association of different kinds of cystic lung lesions and malignant tumors and their possible pathogenetic relationship. In this paper we draw attention to the development of malignant neoplasia in congenital cystic adenomatoid malformation in adults and its diagnostic problems.

Adenocarcinoma, Bronchiolo-Alveolar↗

Lymphoepithelioma-like carcinoma of the lung.

A 47-year-old Caucasian female was admitted to the hospital with a suspicious lesion in the right lower lobe of the lung. At frozen tissue sections a malignant tumour was found which, after special stains and immunohistochemical investigations, was diagnosed as lymphoepithelioma-like carcinoma. Non-Hodgkin's lymphoma and metastasis of a nasopharygeal carcinoma could be excluded by immunohistochemical stains and clinical examination. The tumour cells and the infiltrating lymphocytes were negative for Epstein-Barr virus (EBV) as revealed by in situ hybridization (ISH) and polymerase chain reaction (PCR). A reevaluation of the literature showed an interesting and surprising fact: in all lung cases, so far reported, the tumour cells were positive for EBV in Asians and negative in Caucasians. Due to the high prevalence of EBV infections in the Asian population it might be speculated, that EBV positivity could be an epiphenomenon in Asian cases of lymphoepithelioma-like carcinoma of the lung.

Base Sequence↗

[HIV-associated histoplasmosis with pulmonary manifestation in Europe].

A 35-year-old man developed weight loss, lower abdominal pain, diarrhoea, cough, fever and general deterioration in his health. He had been born and resident in the USA until 1991, when he moved to Germany. Since 1991 he had known that he was HIV-positive. The chest radiograph showed bilateral diffuse spotty marking and a rounded cardiac silhouette, the latter echocardiographically due to pericardial effusion. Tuberculostatic drugs were started because miliary tuberculosis was suspected. But as his condition worsened and he was thought to have Pneumocystis pneumonia high doses of co-trimoxazole were administered. Perbronchial lung biopsy showed nonspecific chronic inflammatory changes. Periodide acid-Schiff reaction and Grocott staining demonstrated numerous histoplasma in alveolar macrophages and connective tissue. The organism was also cultured from bronchial secretions. Treatment was now changed to itraconazole (400 mg daily), 2 weeks later changed to liposomal amphotericin B (100 mg daily) because of renewed fever. After 6 weeks the patient became free of symptoms and the radiological changes had largely regressed. To prevent recurrence, treatment with itraconazole (400 mg daily) is being continued.

AIDS-Related Opportunistic Infections↗

Prognostic importance of human papilloma virus typing in squamous cell papilloma of the bronchus: comparison of in situ hybridization and the polymerase chain reaction.

Thirty-one solitary bronchial squamous cell papillomas (SCPs) with variable degrees of dysplasia, one combined with larynx papilloma and small cell carcinoma in the contralateral lung, and 12 papillomas combined with invasive squamous cell carcinomas (SCCs) were investigated for the presence of human papilloma virus (HPV) DNA by in situ hybridization (ISH) and the polymerase chain reaction (PCR). Benign SCPs showed an association with HPV type 11 and rarely with type 6, whereas type 16 or 18, sometimes in combination with type 31/33/35, was found in SCPs associated with SCCs. In one patient HPV type 18- and 31/33/35-positive benign SCP preceded the recurrence of HPV 18-positive SCP (this time combined with carcinoma) by 2 years. Patients with SCP exhibiting HPV 16 or 18 positivity are at high risk for the development of SCC. Virus typing seems to be a better prognostic indicator than grading of dysplasia or age relationship. Virus typing by the PCR is more sensitive compared with ISH, but positive cells cannot be determined; ISH is less sensitive than the PCR but permits a definite designation of the cell types that have integrated HPV sequences into their DNA. Our data suggest that HPV typing should be performed in every bronchial SCP.

Adult↗