No abstract

Pulmonary carcinoids (PC) are separated into typical (TC) and atypical carcinoids (ATC). However, the biological behavior cannot be reliably predicted, and in small biopsies differential diagnosis can be challenging. To provide a basis for a grading approach, we analyzed mitoses and the proliferative index (PI; Ki-67) of 200 PC specimens (TC: n = 114; ATC: n = 86). To define suitable diagnostic and to screen for putative therapeutic markers, CD56, CD57, CD99, CD117, TTF-1, synaptophysin, chromogranin A, CK 18, KL-1, epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (Her-2/neu), somatostatin receptor subtype 2A (SSTR2A), thymidylate synthase (TS), and excision repair cross-complementation group 1 (ERCC-1) expression was analyzed. A combination of synaptophysin and cytokeratins is the most sensitive marker panel for PC with unclear histomorphology. Predictive phenotyping revealed that SSTR2A is expressed in >80% of all PC and may be used both, as a diagnostic marker for imaging approaches and as a predictive marker for octreotide-based therapies. We introduced a grading system distinguishing between PC with low and highly aggressive biological behavior similar to the grading system for gastrointestinal neuroendocrine tumors. The system is superior to the classical separation into TC and ATC. This study indicates that PI in addition to mitotic count may improve prediction of the biological behavior of PC and should be validated in prospective studies.

Pulmonary carcinoids are infrequent neoplasms of the lung that normally display a less aggressive biological behavior compared to small cell and non-small cell lung cancers. Approximately 15-25% of carcinoids, in particular atypical carcinoids, show lymph node metastasis and have a worse prognosis than their non-metastasized counterparts. To date, there is no morphological or molecular marker that may help to differentiate between carcinoids that metastasize and carcinoids of identical differentiation that show only local tumor growth. In this study, we analyzed 7 metastasized and 10 non-metastasized pulmonary carcinoids for chromosomal and microsatellite instability in order to determine whether microsatellite instability or chromosomal imbalances are associated with metastasis. Due to the rare occurrence of metastasized carcinoids we compared our results of chromosomal instability with the hitherto published comparative genomic hybridization (CGH) profiles of pulmonary carcinoids, for which information about the absence or presence of metastasis was available. While microsatellite instability was not detected we found chromosomal instability as a common event in pulmonary carcinoids with an increase of frequency and extent of chromosomal alterations in atypical and metastasized carcinoids. These findings are in accordance with the collected and herein compiled data of previous studies and indicate increasing numbers of chromosomal imbalances to play a role in the sequential process of tumor development and metastasis.

We retrospectively analysed 301 patients with diffuse malignant pleural mesothelioma (235 male, 66 female; median age 59 years). Prognosis depended significantly on patient age, evidence of pain, loss of weight, tumour cell type, stage, local and distant metastasis, involvement of peritoneum and surgical treatment. The overall median survival rate was 238 days, after extended pleuropneumonectomy 284 days, and after decortication 315 days - significantly better than the prognosis in patients without surgical treatment or exploratory thoracotomy. Pleuropneumonectomy should only be considered in young patients with an epithelial cell-type tumour (possibly with adjuvant chemotherapy). Decortication seems nowadays to be the treatment of choice.

Surgery forms part of a combined oncological concept in the management of pulmonary metastases. The following questions are relevant for its role: Does survival depend on the type of primary tumor? Are there any prognostic factors? What are the limits on radical resection? We analyzed retrospectively 657 patients who had undergone 759 resections of pulmonary metastases between 1973 and 1990. After conducting in vitro and in vivo experiments with the non-contact neodymium aluminum garnet (Nd-YAG) laser with a generating and delivery power of 10-120 W at the site of operation for 0.1-9.9 s, we have treated 65 patients by laser resection and/or vaporization since January 1990. Our preferred surgical approach was median or transverse thoracotomy. The 5-year survival of all resected patients was 30%, ranging from 21% (soft tissue sarcoma) to 60% (testicular carcinoma). Statistically significant differences in prognosis were seen related to the type of primary tumor, the disease-free interval, the caval or portal type of metastatic spread, the number of metastases and the potential degree of radical resection. The potential degree of conventional radical resections (wedge, anatomical sub-/segmental) was negatively influenced by the number of metastases (n > 9: 79% "radical" surgery = 38% 5-year survival). Laser treatment allowed parenchyma-preserving resection in cases of metastases of more than 0.5 cm in diameter, and vaporization in smaller ones. Resection with the intention of achieving complete remission was possible in up to 72 unilateral metastases. The complication rate was comparable to conventional resections.