Papillary muscle injury after blunt chest trauma.

In many cases blunt chest trauma involves cardiac lesions, such as pericardial effusion, aneurysma dissecans, or valvular rupture. Early diagnosis with routine transthoracic and/or transesophageal echocardiography is essential to prevent a fatal outcome. In the case reported, a previously healthy 68-year-old woman fell 7 meters from the roof of a barn and sustained blunt injury to the chest as well as fractures of the face. Physical examination revealed a systolic murmur at the cardiac apex, and chest x-ray film showed a severe pulmonary edema. Transesophageal echocardiography demonstrated a ruptured anterolateral papillary muscle with fourth degree mitral insufficiency. An immediate mitral valve replacement was necessary.

[Development of a thyroid carcinoma after irradiation of the head/neck region]. / Entwicklung eines Schilddrüsenkarzinoms nach Bestrahlung des Kopf-/Halsbereiches.

HISTORY AND CLINICAL FINDINGS: A 73-year-old woman was hospitalised because of increasing dyspnoea and hoarseness after a bout of acute tracheobronchitis. She had been receiving levothyroxine for a growing grade III nodular goitre. At the ages of 26 and 29 she had been treated for cervical lymph node tuberculosis with local excision and percutaneous radiotherapy of 8 Gy each time. On examination she was found to have a bulging neck profile and a hard, practically immobile node in the left lobe of the thyroid. INVESTIGATIONS: Laboratory tests showed a euthyroid metabolic state, while ultrasound demonstrated a mass. 40 mm in diameter, scintigraphically a cold nodule. A fine-needle biopsy was cytologically highly suspicious of neoplasm. TREATMENT AND COURSE: Surgical exploration of the neck and mediastinum revealed an insular follicular carcinoma (10 cm in diameter), involving the right recurrent laryngeal nerve and surrounding the brachiocephalic trunk. The latter had to be removed and a Gore-Tex graft was interposed. Postoperative radiotherapy was given (150 mCurie I131). CONCLUSION: An enlarging nodular goitre, occurring after a latent period of years following radiotherapy to the neck region for benign and (or) malignant disease, especially when it had been administered in childhood or young adulthood, should raise the suspicion of a radiogenic thyroid carcinoma. Definitive diagnosis by fine-needle biopsy is essential.

Primary malignant ectomesenchymoma of the orbit.

Malignant ectomesenchymoma is a rare soft tissue tumor of the childhood believed to arise from a remnant of pluripotential migratory neural crest cell (ectomesenchym) and composed of both a mesenchymal element (most often embryonal rhabdomyosarcoma) and a neuroectodermal element (ganglioneuroma, schwanomma neuroblastoma or melanocytic cells). Reported sites of origin are the abdomen, perineum or scrotum, the extremities, the middle ear, nasopharynx, face, and neck. Herein we report a new case of an orbital ectomesenchymoma studied by means of histochemistry and immunohistochemistry in order to increase the morphologic and histogenetic knowledge of this peculiar tumor and its significance concerning the differential diagnosis.

Histological determinants of the vascular surface in prostatic carcinoma.

This study was performed to analyse the correlation between vascular surface (VS), tumour grade and stage and relative proportion of tumour cells within the tumour stroma. Specimens of 41 prostatic carcinoma were immunostained using Factor VIII-related antigen. The VS was assessed by means of stereology. In tumour-free prostatic tissue the VS was 6.7 +/- 0.4 mm-1. In pT2 tumours this value was significantly increased to about 12 mm-1. With rising pT stage the VS significantly decreased to values of 4 in pT4 tumours. In G1 tumours the VS was 14.6 mm-1 and significantly decreased with decreasing grade of differentiation. No significant difference was obtained between pN0 and pN+ cases. A close positive correlation (r = 0.59, P < 0.001) existed between the VS and the relative proportion of tumour cells within the tumour, whereas a strong negative correlation was found between the VS and the relative amount of tumour stroma (r = 0.81, P < 0.001). The VS mainly depends on tumour differentiation and pT stage, i.e. the tumour size and the relative proportion of stroma and tumour cells within the tumour. These results are consistent with those obtained in experimental tumours. Assessment of the VS is therefore of interest in studies of tumour biology; it is of no use in predicting lymph node metastasis.

Anatomical basis for pelvic lymphadenectomy in prostate cancer: results of an autopsy study and implications for the clinic.

PURPOSE: Pelvic lymphadenectomy remains the most reliable method to prove lymph node metastases in prostate cancer. However, evaluation of lymphadenectomy to be complete and sufficient as judged by the number of removed lymph nodes in hampered by the fact that, in contrast to other malignancies (for example breast or gastric cancer), anatomical studies investigating the regular and average number of pelvic lymph nodes are missing. We established an anatomically based standard for pelvic lymphadenectomy. MATERIALS AND METHODS: Standard pelvic lymphadenectomy was performed on 30 human cadavers and 59 consecutive patients with clinically organ confined prostate cancer during radical retropubic prostatectomy. Number, size and topography of the lymph nodes were noted separately for each anatomical region of both iliac fossas. RESULTS: The mean number of lymph nodes removed in the autopsy series plus or minus standard deviation (22.7 +/- 10.2, range 8 to 56) was nearly identical to that from patients with prostate cancer (20.5 +/- 6.6, range 10 to 37) but striking interindividual differences were observed. Patients with prostate cancer demonstrated enlarged nodes regardless of whether they did or did not contain tumor. Interestingly, pelvic lymph node metastases were more common on the left side regardless of the primary tumor site. CONCLUSIONS: Approximately 20 pelvic lymph nodes may serve as a guideline for a sufficient standard pelvic lymph node dissection. Lymphadenopathy in prostate cancer patients is not always a result of metastases but, rather, hyperplastic or regressive alterations. A preferential distribution of lymph node metastases along the left iliac vessels regardless of the primary tumor site in the prostate warrants further investigation.

Melanoma in situ versus melanocytic hyperplasia in sun-damaged skin. Assessment of the significance of histopathologic criteria for differential diagnosis.

For differentiation of melanoma in situ (MIS) from melanocytic hyperplasia (MH) in sun-damaged skin, several criteria have been proposed. To assess sensitivity and specificity of those criteria, we examined the epidermis adjacent to 50 consecutive basal cell carcinomas and 50 MISs in skin with significant solar elastosis. The most valuable criteria for the diagnosis of MIS, as opposed to MH, were presence of nests of melanocytes, irregular distribution of melanocytes, descent of melanocytes far down adnexal epithelial structures, irregular distribution of pigment, presence of melanocytes above the junction, a high number of melanocytes, pleomorphism of melanocytes, and atypical nuclei of melanocytes. Other criteria, e.g., collapse of cytoplasm around nuclei of melanocytes; flattening of rete ridges; differences in the area, shape, and contour of nuclei of melanocytes as assessed by nuclear morphometry; and presence of melanocytes stained by HMB-45 and Ki-67/MIB-1 monoclonal antibodies, were found to be of low or no value for differential diagnosis.

Assessment of the vascularization in prostatic carcinoma: a morphometric investigation.

Prostatic carcinoma obtained from 41 patients (pT2N0, 5; pT2N+, 2; pT3N0, 16; pT3N+, 16; pT4N0, 1; and pT4N+, 1) ranging from 45 to 79 years of age were investigated in the present study. A total of 410 tumor areas of different grades were analyzed (G1, n = 116; G2, n = 98; and G3, n = 196). Vascular structures were labeled immunohistochemically using factor-VIII-associated antigen. The vascular surface density (VSD), the microvessel number (NVES), and the maximum microvessel number (NVES-MAX) were assessed by means of stereology, and the results were related to tumor stage, nodal status, and grade of differentiation. NVES and NVES-MAX showed a significant increase with rising pT stage ranging from 25.5 +/- 1.48 in controls to 135.0 +/- 5.5 microvessels/mm2 in pT4 tumors. Discrimination of different pT stages was more accurate with NVES-MAX. The VSD was significantly higher in pT2 tumors compared with controls, whereas there were no significant differences between pT3 tumors, pT4 tumors, and controls, although the values in pT3 and pT4 tumors were distinctly lower than in pT2 tumors (P < .05). The VSD and the NVES were not able to discriminate between the pN0 and the pN+ group. Both parameters were slightly higher in patients with metastatic disease. Only NVES-MAX values differed between the two groups with an average of additional 21 microvessels/mm2 in the pN+ group (P < .05). Concerning the grade of tumor differentiation the VSD continuously decreased from G1 (14.58 +/- 2.24 mm(-1) to G3 tumor areas (5.41 +/- 1.46 mm(-1). Only G1 tumors showed significant differences compared with controls (6.65 +/- 0.38 mm(-1). The NVES increased with rising tumor grade with significant differences between all four groups ranging from 25.5 +/- 1.5 in controls to 136.9 +/- 37.2 microvessels/mm2 in pT4 tumors.

Expression of gp100 in melanoma metastases resected before or after treatment with IFN alpha and IL-2.

The melanosomal protein gp100 was recently described as an antigen associated with tumor rejection in adoptive immunotherapy using tumor-infiltrating lymphocytes. In this study, we investigated whether the expression of gp100 in melanoma cells correlates with responsiveness to treatment with interferon-alpha and interleukin-2. Using the monoclonal antibody HMB-45 recognizing gp100, we examined metastatic tissue resected before therapy in 44 patients with melanoma including 9 patients with subsequent complete or partial remission. A very heterogeneous pattern of gp100-expression was found between patients, but the percentage of gp-100 positive cells in different metastases resected from the same patient was rather constant. This suggests that the gp100 expression determined in a single metastasis may be judged as being representative for other metastatic lesions of a patient. We found no correlation between expression of gp100 and responsiveness to subsequent immunotherapy. Our results show that the lack of gp100 before therapy is not associated with decreased responsiveness to subsequent cytokine treatment.

Quantitative assessment of vascular surface density in renal cell carcinomas.

OBJECTIVE: To evaluate the extent of vascularization by assessing vascular surface density in renal cell carcinomas (RCCs) of different nuclear grades, and in normal renal cortex and medulla. MATERIALS AND METHODS: Specimens of 79 RCCs of different nuclear grades (16 of G1, 42 of G2 and 21 of G3) were immunostained with the lectin Ulex europaeus agglutinin-I (UEA I). The vascular surface density of tumour tissue was assessed stereologically using a test grid at x400 magnification and compared to the values obtained in normal renal tissue. RESULTS: G3 tumours had a lower vascular surface density than had G1 and G2 RCCs and normal renal tissue of the cortex and medulla (P < 0.001, respectively). G1 tumours had a significantly higher vessel density than had normal medullary parenchyma and G2 carcinomas (P < 0.001). Vessel density was not significantly different among G1 tumours and cortical parenchyma in controls and among normal medullary tissue and G2 tumours. Statistical analysis showed that the vascular surface density was independent of tumour stage and size and the age and sex of the patients. CONCLUSION: The degree of vascularization in RCCs decreased with their grade of differentiation, suggesting that the extent of neovascularization in tumour tissue reflects the relationship between tumour cell proliferation and vascular growth. The values of vascular surface density in normal renal tissue of the cortex and medulla partially overlapped with those obtained in tumour tissue.

Clear cell carcinoma of the gallbladder. A histological and immunohistochemical study.

Three cases of malignant clear cell carcinoma of the gallbladder were studied immunohistochemically with a broad panel of antibodies, especially cytokeratins, in order to better characterize their histogenesis. The advantage of immunohistochemistry in the differential diagnosis between clear cell carcinoma of the gallbladder and other clear cell carcinomas metastatic to the gallbladder such as renal cell carcinoma is discussed.

Quantitative analysis of parenchymal and vascular alterations in NO2-induced lung injury in rats.

Nitrogen dioxide (NO2), the oxidation product of nitric oxide (NO), is a reactive free radical forming gas, the inhalation of which has been reported to induce severe damage to distal airways. In order to quantify dose and time course of parenchymal and vascular damage, rats were exposed to 5, 10 and 20 ppm NO2 for 3 and 25 days, followed by quantitative histology and morphometry of the lung. Histological investigations of the short-term exposed animals showed structural alterations extending from slight interstitial oedema after exposure to 5 ppm, to epithelial necrosis and interstitial inflammatory infiltration after exposure to 10 ppm, and an additional intra-alveolar oedema after 20 ppm. The pulmonary arteries disclosed no qualitative changes, such as muscularization of intra-acinar vessels. Long-term exposure to 10 ppm and 20 ppm NO2 resulted in emphysema and slight centrilobular interstitial fibrosis. Morphometric analysis revealed the alveolar surface density to be significantly diminished after short-term exposure to 20 ppm NO2 and long-term exposure to 10 and 20 ppm NO2. The medial thickness of pulmonary arteries was significantly increased after short- and long-term exposure to 20 ppm NO2 and long-term exposure to 10 ppm NO2. In the 5 ppm short- and long-term exposure groups the pulmonary arterial medial thickness was significantly decreased compared to controls. Correlation analysis revealed a negative correlation between average medial thickness and alveolar surface density (coefficient of correlation: -0.56). We conclude that the extent of NO2-induced pulmonary parenchymal and vascular alterations are closely related and concentration- and time-dependent.

In vitro and ex vivo expression of nucleolar proteins B23 and p120 in benign and malignant epithelial lesions of the prostate.

The expression of two specific nucleolar antigens, p120 and B23, has been investigated in the prostatic carcinoma cell line LNCaP as well as in 40 frozen and 40 formalin-fixed tissue samples of benign and malignant prostatic lesions (15 benign hyperplasias, 5 grade 1, 15 grade 2, and 5 grade 3 carcinomas). In vitro, immunoreactivity of p120 was confined to nucleoli of proliferating cells, with virtually no negative staining during S and G2/M phases. Unlike p120, B23 was expressed in the nucleoli of all LNCaP cells independently of growth and cell cycle phases. Hence, B23 was detectable in all stromal as well as in normal and malignant epithelial prostatic cells, both in fresh and in formalin-fixed tissue sections after microwave treatment. In contrast, the immunoreactivity of p120 was almost completely restricted to the nucleoli of prostate carcinoma cells: frozen sections of benign prostatic hyperplasia (n = 15) were either totally negative for p120 (n = 13) or had a low percentage of positively stained cells (labeling index = 3.3% in 3 cases). In the carcinoma group 76% (19/25) of the specimens were p120 positive, and there was a significant rise of labeling index from 18.1% in grade 1 to 82.2% in grade 3 carcinomas (P < 0.001). In contrast to B23, p120 could not be reliably demonstrated in formalin-fixed and paraffin-embedded tissue. We therefore conclude that anti-B23 is a general marker of nucleoli, whereas expression of p120 appears to correlate with "hyperactivity" of the nucleolus and provides a new tool for flow cytometrical and immunohistochemical assessment of nucleolar activity in tumor pathology.

Isolated clinical syndrome of primary aldosteronism in a patient with adrenocortical carcinoma. Case report and review of the literature.

Primary carcinoma of the adrenal cortex is an extremely rare neoplasm, accounting for an estimated 0.05-0.2% of all malignancies. Hormonally functioning tumors occur in about 50% of patients with Cushing's syndrome (50%), virilism (30%) and feminization (12%) being the most common clinical manifestations. Isolated aldosteronism caused by adrenocortical carcinoma is found in about 1-3% in patients with the clinical signs of Conn's syndrome. The only preoperative feature suggesting malignancy is a size of more than 5 cm in computed tomography. We report a rare case of a 29-year-old man with biochemically proven primary aldosteronism as the unique manifestation of a carcinoma of the right adrenal cortex.

Nuclear morphometry of soft tissue tumors of fibrous origin.

In this study we investigated the diagnostic significance of a set of different morphometric nuclear parameters in the differential diagnosis of soft tissue tumors. Nuclear area, the standard deviation of the nuclear area, the shape factor and other parameters such as Feret's Diameter and Martin's Radii were assessed using a computer assisted image analyzer system. A statistically significant difference (p < 0.01) between benign and malignant tumors and tumor-like lesions could be confirmed for the nuclear area and the standard deviation of the nuclear area, with the significance level being lower (p = 0.5) for the latter parameter. The shape factor also discriminated between the examined groups. Reclassification of the assessed histological diagnosis was performed by linear discriminant analysis using all possible combinations of the different nuclear parameters. This procedure disclosed an increasing rate of correctly reclassified cases with rising number of parameters applied. We conclude that the assessment of nuclear parameters may be helpful in the correct diagnosis and differential diagnosis of soft tissue tumors and tumor-like lesions of fibrous origin.

Assessment of proliferative activity in type II pneumocytes after inhalation of NO2 by AgNOR-analysis.

Adult male Sprague Dawley rats were exposed to 0.8, 5 and 10 ppm NO, alternatively for 1 or 3 days. After exposure the proliferative activity of the airway epithelium was assessed by means of BrdU incorporation and AgNOR-analysis at three different airway levels--in the bronchial, the bronchiolar epithelium and in Type 2 cells. The BrdU-labeling index (BrdU-LI), and AgNOR-number (AgNOR-N) were used to quantify the epithelial proliferation. Cytologic specimens of Type II cells showed a significant increase of the AgNOR-number and BrdU-LI after exposure to 5 ppm NO2 for 3 days and 10 ppm for 1 and 3 days. In the bronchiolar epithelium both, the AgNOR-number and BrdU-LI were significantly elevated in all the exposure groups. In the bronchial epithelium a significant response of the AgNOR-number was found after exposure to 10 ppm for 3 days. The correlation between AgNOR-number and BrdU-LI was 0.78 (p < 0.005).

[Focal necrotising vasculitis of the testis. Testicular manifestations of immunologic diseases in differential diagnosis of testicular cancer]. / Fokale nekrotisierende Vaskulitis des Hodens. Testikuläre Manifestationen immunologischer Erkrankungen in der Differentialdiagnostik des Hodentumors.

We report on the case of a 31-year-old male patient with focal testicular vasculitis as the only clinical manifestation of endangiitis obliterans (Winiwarter-Buerger disease), who presented with acute scrotal pain and swelling suggestive of a testicular tumor. Doppler sonography revealed significantly increased vascularization at the borders of the lesion, which rather indicated a vascular process; however, the presence of solid areas meant that the possibility of testicular cancer could not be excluded. Left inguinal orchiectomy was performed. The surgical specimen revealed histological patterns compatible with endangiitis obliterans; Raynaud phenomenon was the only sign of systemic disease, and no other organs were found to be affected. Despite the high sensitivity and specificity of ultrasound/Doppler sonography, in the differential diagnosis of an unexplained testicular mass surgical exploration is still mandatory. The different types of focal vasculitis are described and discussed with reference to the literature.

[Nematode larva migrans. On two cases of filarial infection]. / Wandernde Nematodenlarven. Uber zwei Fälle von Filarienbefall.

With rapid air travel, so-called parasitic infections are becoming more important in northern hemisphere and temperate climates. Parasitic disease is usually taken to imply infections caused by protozoa and helminths. The most important helminthic infections in man and with world-wide incidence are schistosomiasis, hookworm, and filariasis. We report the clinico-pathological findings of two patients with filarial infection of soft tissue and lymphatic nodes.