Clinical and morphological aspects of adenocarcinomas of the intestinal type in the inner nose: a retrospective multicenter analysis.

Clinical and histological parameters from 117 patients with wood dust-related sinonasal adenocarcinomas of intestinal type (ITAC) were analyzed and correlated with a follow-up period of 5 years at least. The rate of survival for 5 years was 53.1 % and for 10 years 30.2 %. Only 33 patients were free of disease. 74.2 % of patients with recurrences died in relation to ITAC. As expected, tumors of T4-category had the worst prognosis. The mucus content of a tumor was the most important histological parameter. Endonasal methods of surgery had no more positive survival rates after 5 years. An effect of radiotherapy has to be in discussion. The high incidence of tumor recurrences requires control examinations consistently.

Metastatic behaviour of sinonasal adenocarcinomas of the intestinal type (ITAC).

The relative frequency of regional lymphogenic versus distant hematogenic metastases was evaluated in 369 patients with sinonasal adenocarcinoma of the intestinal type (ITAC). We assessed the results of neck dissections for a limited number of patients undergoing this surgical intervention. 117 ITAC patients were followed up for at least 5 years. Neck dissections were performed in 18 cases (15 primary and 3 secondary operations), 4 of which revealed carcinoma-positive lymph nodes. Metastases in lymph nodes were also diagnosed clinically in three other patients adding up to a total of seven individuals (6 % of 117) with lymphogenic metastases. In comparison, distant hematogenic metastases were identified in 15.4 % of these 117 patients. In the second group of 252 patients, the occurrence of distant hematogenic metastases and colorectal adenocarcinomas was registered but no formal follow-up procedure was applied. 50 neck dissections were performed in this group, 46 of which exhibited no histological evidence for metastases in lymph nodes, while in 1 case they were carcinoma-positive. Three additional cases showed clinical signs of metastases in regional lymph nodes. Taken together, our observations indicate that regional lymphogenic metastases are rather rare (about 2 %) in patients with sinonasal adenocarcinoma of the intestinal type. Therefore, the surgery of neck dissection appears not advised as routine intervention in these cases. ITAC patients show a normal prevalence of colorectal adenocarcinomas.

Diagnosis of invasive fungal infections in hematology and oncology--guidelines from the Infectious Diseases Working Party in Haematology and Oncology of the German Society for Haematology and Oncology (AGIHO).

Invasive fungal infections (IFIs) are a primary cause of morbidity and mortality in patients with hematological malignancies. Establishing a definite diagnosis of IFI in immunocompromised patients is particularly challenging and time consuming, but delayed initiation of antifungal treatment increases mortality. The limited overall outcome has led to the strategy of initiating either 'empirical' or 'preemptive' antifungal therapy before the final diagnosis. However, diagnostic procedures have been vastly improved in recent years. Particularly noteworthy is the introduction of newer imaging techniques and non-culture methods, including antigen-based assays, metabolite detection and molecular detection of fungal DNA from body fluid samples. Though varying widely in cancer patients, the risk of IFI is highest in those with allogeneic stem cell transplantation and those with acute leukemia. The AGIHO presents recommendations for the diagnosis of IFIs with risk-adapted screening concepts for febrile episodes in patients with haemato-oncological disorders.

Occupational risks for adenocarcinoma of the nasal cavity and paranasal sinuses in the German wood industry.

OBJECTIVES: To examine the risk of wood dust and chemical exposures for adenocarcinoma of the nasal cavity and paranasal sinuses (ADCN) among German wood workers. METHODS: An industry-based case-control study with 86 male ADCN cases and 204 controls was conducted in the German wood-working industries. Cumulative and average wood-dust exposure was quantified with a job-exposure matrix based on wood-dust measurements at recent and historical workplaces. Probabilities of exposure to wood preservatives, stains, varnishes, and formaldehyde were semi-quantitatively rated. Odds ratios and 95% confidence intervals were calculated with logistic regression analysis conditional on age and adjusted for smoking and other factors. For estimating the risks of either wood dust or chemical additives, the authors additionally adjusted for the corresponding co-exposure. RESULTS: ADCN occurred relatively more frequently among wood workers that had ever worked as cabinet makers or joiners (OR 2.96, 95% CI 1.46 to 6.01) than as saw millers (OR 0.15, 95% CI 0.03 to 0.68). Average exposure to inhalable wood dust >/=5 mg/m(3) was associated with a high risk (OR 48.47, 95% CI 13.30 to 176.63) compared to levels below 3.5 mg/m(3). Assuming 40 years of exposure under these concentrations, the corresponding OR was 4.20 (95% CI 1.69 to 10.43). Exposure between 3.5 and 5 mg/m(3) was also found to pose a risk (OR 10.54, 95% CI 3.34 to 33.27). Exposure to pigment stains before 1970 was associated with an increased risk (OR 3.03; 95% CI 1.11 to 8.26). No significant associations were estimated for wood preservatives, varnishes, and formaldehyde. CONCLUSIONS: The authors found an elevated ADCN risk for exposure to inhalable wood dust above 3.5 mg/m(3). The rareness of the disease does not allow the exclusion of risk below that concentration. For pigment stains, there is evidence for an association of historical exposure with the development of ADCN in German wood workers.

Mitosis counts: reproducibility and significance in grading of malignancy.

The interindividual and intraindividual reproducibility of mitosis counts was investigated in 10 cases of malignant non-Hodgkin's lymphoma. With thickness of histologic sections, staining, and the area measured kept constant, the degree of reproducibility was found to be dependent largely on the experience of the investigator. For investigators at similar levels of experience, the mitosis rates obtained were of the same order of magnitude. However, defined mitosis counts do not allow unrestricted grading of malignancy, even after elimination of methodologic pitfalls. Proliferation rates of malignant tumors cannot be expected to be constant due to biologic conditions, such as varying metabolic activity or tumor cell heterogeneity.

Mucoid cytoplasmic inclusions in urothelial carcinomas.

To date, mucoid cytoplasmic inclusions in urothelial carcinomas have rarely been noted. However, we were impressed by the fact that these corpuscles are readily detectable in numerous urothelial neoplasms. Therefore, a histologic analysis of 100 cases of urothelial carcinomas was performed. Overall, 37 cases revealed periodic acid-Schiff-positive cytoplasmic inclusions. These were observed in 14% of grade 1, 49% of grade 2, and 63% of grade 3 carcinomas. The inclusions were histochemically, immunohistochemically, and ultrastructurally identified as cytoplasmic deposits of mucoid materials. Two types of deposits, condensed and noncondensed, could be distinguished. The demonstration of mucoid deposits in otherwise poorly differentiated metastatic carcinomas may be of some differential diagnostic importance insofar as urothelial carcinoma has to be considered as the possible primary tumor.

Changes in mitotic rate and cell cycle fractions caused by delayed fixation.

The mitosis frequency and flow cytometric data of malignant neoplasms are important, both for diagnosis and for prognosis. It is unclear to what extent these factors are affected by a delay in the fixation of tumor biopsies. We have thus studied the mitotic activity and DNA content in human soft-tissue sarcoma xenotransplants, fixed for periods of 5 minutes and 3, 6, 9 and 12 hours after biopsy. On average, the mitoses counted by two observers were 13% and 10% below initial values after 3 hours, and decreased by 46% and 39% after 12 hours. The mitosis decrease was related to the degree of mitotic activity of individual tumors, and was minimal in the sarcomas with the lowest mitotic rate. These results were reproducible. However, numerous pyknotic mitotic figures were observed, so the decrease in counts is largely due to their reduced identifiability, and only partly attributable to a completion of the cell cycle. Well-preserved mitotic figures demonstrable after 12 hours appear to indicate that the proliferation activity only gradually decreases in unfixed biopsies. The flow cytometric data did not change substantially; only a slight increase in the G2 + M-phase fraction was observed. General conclusions from the results are limited by the fact that the investigated sarcomas had a higher mitotic activity than most carcinomas. Nevertheless, early fixation of biopsies is desirable to accurately measure mitosis counts for the grading of malignancy.

Nuclear grading of renal cell carcinomas--is morphometry necessary?

Comparative investigations of subjective with objective nuclear grading methods of renal cell carcinomas are almost completely lacking. Therefore, we graded 94 cases of this carcinomas by a simple, subjective microscopical estimation as well as by a morphogenetic measurement of nuclear area. Both procedures proved prognostically useful, but the best results were achieved by morphometry. By this method three prognostic groups of renal cell carcinoma were found, provided that the borderlines were drawn at 28 microns 2 and 60 microns 2, respectively. Particularly favourable and unfavourable cases could be separated from average ones, if the means and standard deviations of both the nuclear areas and the diameters were evaluated. Overall, morphometric nuclear analyses are highly desirable, if, for example, morphological data are to be used in the context of prognostic or therapeutic studies on renal cell carcinoma. However, there is a broad distribution of the values for individual cases so that, tumour-biologically, no exact demarcation of prognostically different groups can be expected.

Malignant granular cell tumor.

The malignant granular cell tumor ist a rare soft tissue neoplasia which is chiefly localized in the sceletal muscles. The uncertain histogenesis gave rise to different terms. The clinical course is often protracted but fatal. Diagnosis, differential diagnosis, and treatment are discussed in the light of a case report concerning a malignant granular cell tumor in a 28-year-old man.

Primary gastric non-Hodgkin's lymphoma: a clinicopathological study of 41 patients.

Pathological findings in 41 patients (male/female ratio: 1.3/1) with primary localized gastric non-Hodgkin's lymphoma (NHL) were retrospectively studied and correlated with survival. The median observation period after diagnosis was 32 (0-189) months. Nineteen patients were low-grade NHL, all but one B-cell lymphomas of the mucosa-associated lymphoid tissue (MALT) type. Twenty-two patients had primary (n = 7) or secondary (n = 15) high-grade lymphomas; Musshoff stage IE was found in 29 and IIE in 12 cases. The median age at diagnosis was 61 years (range, 26-88 years), and proliferation, measured by the number of mitosis and Ki-67 antigen positivity (MIB-1), was high or moderately high in 24 cases and low in 17 cases. Follicular lymphatic hyperplasia could be found in 25 of 34 evaluable cases, more often in low-grade than in high-grade NHL. Most of the patients were treated by resective surgery and additional ratio- or chemotherapy. Thirteen patients (31%) died (median survival: 10 months), 5 of them within 3 months after surgery owing to postoperative complications. Survival was superior, though not statistically significant, in low-grade lymphomas. Our retrospective analysis of heterogeneously treated gastric lymphomas reveals that gastric lymphomas, especially of the low-grade MALT type, often remain a localized disease with a good long-term prognosis. Our study confirms previous reports indicating that lymphomas of the MALT type represent a specific clinicopathological entity.

Malignant progression of angioimmunoblastic lymphadenopathy.

In a 79-year-old woman, the progression of angioimmunoblastic lymphadenopathy with dysproteinemia (AILD) to malignant lymphoma was observed within one year after diagnosis. Three biopsy specimens from lymph nodes and one tonsil, obtained at intervals of several months, showed an increasing destruction of the tissue architecture and the development of histological criteria for a lymphoid neoplasm, which at autopsy was confirmed as a malignant non-Hodgkin's lymphoma. The demonstration of a chromosomally abnormal clone in lymph node derived and the laboratory findings were in agreement with the histological changes and the sequential clinical deterioation. Initially, a symptom-free interval of eight months was achieved with prednisone therapy. However, this treatment failed after the malignant transformation had become evident.

Medical THz imaging: an investigation of histo-pathological samples.

We present a THz investigation of histo-pathological samples including the larynx of a pig and a human liver with metastasis. Our measurements show that different types of tissue can be clearly distinguished in THz transmission images, either within a single image or by a comparison of images obtained for different frequency windows. This leads to the problem that images obtained for different frequencies inherently have a different spatial resolution. An image obtained from two such images by a simple mathematical operation may contain artefacts. We discuss measures to deal with this problem. Furthermore, we investigate the possibility of improving the spatial resolution of THz images. Finally, we present a cw THz imaging system based on a photomixer and an external cavity semiconductor laser that allows for simultaneous two-mode operation. The cw system is less expensive and more compact than conventional time-domain imaging systems.

Mitoses in non-Hodgkin's lymphomas. Frequency and prognostic relevance.

The frequency of mitoses was investigated in 279 lymph node biopsies from untreated patients with non-Hodgkin's lymphomas. The data were correlated with histological subtypes and survival time. It could be shown that the frequency of mitoses increases parallel to the amount of large tumor cells, except for lymphoblastic varieties. The proliferative activity was not influenced by a plasmacytoid differentiation. The nodules of follicular centroblastic centrocytic lymphomas revealed more mitoses than did the diffuse lymphomas of a similar grade of malignancy which shows that the growth pattern must be considered when the frequency of mitoses is interpreted. Immuno- and centroblastic lymphomas exhibited no marked differences with regard to mitotic activity. If all lymphomas are subdivided into three groups according to the mitotic grade alone, three survival curves are obtained that differ significantly from each other. It is concluded, therefore, that the mitotic activity of malignant lymphomas is a useful prognostic parameter that, until now, has received unduly limited attention.

Prognostic significance of vimentin positivity in formalin-fixed renal cell carcinomas.

The aim of the present study was to determine whether vimentin immunoreactivity was of prognostic relevance using the PAP-method on formalin-fixed tissue from 94 renal cell carcinomas (RCC). The vimentin expression was compared with tumour stage, histological grade of malignancy, and survival data. In 28 cases (30%), the tumour cells showed a vimentin positivity. This group showed a more unfavourable prognosis than the vimentin-negative group. Differences were also seen in stage T 3 tumours. The percentages of vimentin-positive cases increased with the grade of malignancy. Vimentin-positive cases showed a particularly unfavourable course in the G 3-group of carcinomas. In individual cases, the prognostic value of vimentin expression is limited by a decreased sensitivity and specificity. In addition, the presence of immunoreactivity apparently is not independent of conventional histological criteria of tumour grading.

Mast cell frequency in soft tissue tumors. Relation to type and grade of malignancy.

A high content of mast cells (MC) is considered characteristic of neurofibromas but not of malignant schwannomas and neurilemmomas. We examined the extent and reliability of this finding by counting MC in 61 peripheral nerve sheath tumors and in 103 non-neurogenic soft tissue sarcomas. We furthermore investigated correlations between the amount of MC and various features of the tumors (e.g. grades of malignancy). Neurofibromas had very high mast cell counts. However, this result only applied to about 70% of these tumors. Malignant schwannomas, malignant fibrous histiocytomas and leiomyosarcomas had remarkably high median values of MC counts with a wide dispersion within the histological groups. Synovial sarcomas were the only group that contained MC in every case, though often in small numbers. In univariate analyses the number of MC was negatively correlated to grades of malignancy, cellularity and mitotic activity of the sarcomas and tended to correlate positively to the amount of myxoid and collagenous connective tissue and lymphocytic infiltrates. Multiple linear regression analysis revealed a significant correlation to the grade of malignancy and the amount of connective tissue.

Ultrastructural evidence for divergent and alternating differentiations in spindle cell sarcoma xenografts.

Seven spindle cell sarcomas, 5 poorly differentiated ones and 2 moderately well differentiated ones, were established on nude mice and long term passaging was done. Sarcoma strains were analysed electron microscopically in an attempt to get further insight in spindle cell sarcoma differentiation pathways. Ultrastructurally, the tumours were classified as malignant peripheral nerve sheath tumour (3/7), leiomyosarcoma (2/7), rhabdomyosarcoma (1/7), and spindle cell sarcoma not otherwise classifiable (1/7). Undifferentiated tumour cells including fibroblastoid ones predominated in most xenografts, whereas cells harbouring cytoplasmic specificities tended to be few in number. Nevertheless, divergent differentiations exhibiting unusual double or triple patterns could be documented ultrastructurally in 12/30 xenografts with juxtaposed myomatous as well as nerve sheath-like cells and, in addition, histiocytoid (MFH-like) elements in 3 of the xenografts. Moreover, sarcoma strains alternated fine structural constellations in the course of passaging, whereby different phenotypes, myomatous, nerve sheath-like, unspecific, or mixed ones, succeeded one another. These findings pursue recent immunohistochemical data on multidirectional sarcoma differentiation by means of electron microscopy. They, furthermore, fit well into the concept of multipotential stem cells as progenitors in mesenchymal differentiation and suggest microenvironment to play a modifying role in the expression of cell differentiation.

[Primary malignant melanoma of the esophagus]. / Das primäre maligne Melanom der Speiseröhre.

We report two cases of primary malignant melanoma of the esophagus. Both were female, 83 and 68 years of age. Both had metastatic spread of the disease at the time of first treatment, either in regional lymph nodes or organ involvement. One patient underwent resection of the tumor (partial esophagectomy). The second patient is alive 22 months postoperatively with metastatic tumor (12/1989), the first died one year after diagnosis. Prognosis of primary melanoma of the esophagus is poor. Though, resection of the tumor is the most promising therapy.

[Systemic fungal infections in hematologic neoplasms. An autopsy study of 1,053 patients]. / Systemische Pilzinfektionen bei hämatologischen Neoplasien. Eine Autopsiestudie an 1053 Patienten.

BACKGROUND: Mycoses are common complications of haematological neoplasias. For successful antimycotic treatment, a knowledge of preferential underlying disease, frequency, species and site of the mycosis is of importance. PATIENTS AND METHODS: Postmortem material comprising clinical data, autopsy protocols and histological sections obtained between 1976 and 1990 from 1,053 patients with leukaemia and malignant lymphomas following antineoplastic therapy was analysed retrospectively. RESULTS: Autopsy revealed systemic mycoses in 184 patients (17.5%). Between 1976 and 1990, the incidence of fungal infections increased from 12% to 30%, most being found in acute leukaemia (24%). Myeloproliferative syndrome (18%), non-Hodgkin's lymphomas (16%), Hodgkin's disease (10%) and plasmocytoma (2.5%) were less frequently associated with mycoses. With no preference for any particular malignancy in evidence, aspergillosis predominated at histology (85 cases), while candidosis occurred in 75 cases. A combination of two mycoses (aspergillosis and candidosis) (14 patients), zygomycosis (eight patients) and cryptococcosis (two patients) were much less common. While aspergillosis caused mostly pulmonary (81 cases) and cerebral (18 cases) infections, candidosis most frequently affected the GI tract (83 cases). The fungal infection was regarded as the main cause of death in some 76% of the cases. An analysis of bone marrow of patients with mycosis (184 cases) revealed a predominance of hypoplasia (54%) over tumour infiltration (34%) and normal bone marrow (12%). In malignancies with no mycoses (869 cases) in contrast, hypoplasia was significantly less common (19%) than infiltration (59%) or normal bone marrow (22%) (p < 0.001). CONCLUSION: The incidence of mycoses in haematological neoplasias in our post mortem series has continued to increase. Bone marrow hypoplasia in particular predisposes to fungal infection. The lungs are the organs of predilection, and aspergillosis is likely to be the infection presenting.