Absence of c-KIT and members of the epidermal growth factor receptor family in refractory germ cell cancer.

BACKGROUND: Germ cell tumors (GCTs) in adolescent and young males are very sensitive to cisplatin-based chemotherapy. However, 10-20% of the patients cannot be cured by currently available therapeutic options. Once a tumor does not respond to cisplatin, current therapeutic modalities offer only a chance for short palliation. Recently, new treatment options that interfere with various receptor tyrosine kinases, including c-KIT and members of the epidermal growth factor receptor (EGFR) family, have been used successfully in chemotherapy-resistant tumors overexpressing c-KIT, ERB-B2, or EGFR. METHODS: We studied the presence of c-KIT and the four members of the EGFR family by immunohistochemistry, as well as by ERB-B2 gene amplification using fluorescent in situ hybridization, in a series of 22 patients with cisplatin-resistant GCTs in search of new treatment targets. The results in these refractory tumors were compared with those of 12 patients with chemosensitive GCTs diagnosed in an advanced metastatic stage. RESULTS: The data obtained in both groups did not differ in any of the investigated biologic markers. c-KIT was detected in the one case of pure seminoma studied and in the seminomatous components of combined tumors. The presence of EGFR was restricted to trophoblastic giant cells and the syncytiotrophoblastic elements of four nonseminomas including one pure choriocarcinoma and to a secondary non-germ cell malignancy, which had developed most likely from a mature teratoma. ERB-B2 was moderately positive in the secondary non-germ cell malignancy, in one mature teratoma component of a mixed nonseminoma, and together with EGFR in the syncytiotrophoblastic cells of a pure choriocarcinoma. Of all samples investigated, this latter case was the only one showing an amplification of the ERB-B2 gene in the syncytiotrophoblasts. ERB-B3 and ERB-B4 were detected rarely. CONCLUSION: The majority of refractory GCTs do not qualify for treatment with new biologic agents targeting the receptor tyrosine kinases EGFR, ERB-B2, or c-KIT. The lack of differences between the tumors of refractory and the responsive patients indicates that overexpression of any of these receptor tyrosine kinases does not contribute to a resistant phenotype in GCTs.

[Massive Gorham-Stout osteolysis of the temporal bone and the craniocervical transition]. / Massive Osteolyse Gorham-Stout des Felsenbeines und des kraniozervikalen Uberganges.

Massive osteolysis Gorham-Stout is a rare, benign but locally aggressive angiomatosis which results in destruction and resorption of bone. The etiology and pathogenesis are undefined. The occurrence of the disease in the skull base is uncommon. A 54-year-old female presented with isolated, one-sided surditas. Eight years before the patient underwent surgery and radiation therapy for treatment of hypopharyngeal cancer. A transtemporal biopsy was taken and a highly vascularized, cystic lesion with destruction of the right occipital and temporal bone and the atlas was found. Histopathology showed thin-walled capillaries with flattened endothelial lining cells. After exclusion of malignant and infectious components the diagnosis of Gorham's disease was established. Review of the literature suggests radiation therapy as the method of choice for stopping the disease's progress. The aim of this case report is to emphasize the Gorham-Stout-Syndrome as a rare differential diagnosis for skull base lesions.

Urinary bladder biopsies in spinal cord injured patients.

STUDY DESIGN: A series of 94 urinary bladder biopsies in spinal cord injured (SCI) patients were histopathologically and statistically analysed. OBJECTIVES: The following hypotheses were examined: (1) The number of clinical bladder infections per year in each patient does not influence the histopathological type of inflammation of the urinary bladder; (2) The duration of the spinal cord lesion does not have a strong effect on the type of inflammation; (3) The different neurological levels (upper and lower motor neuron lesions) do not relate to a specific histopathology. SETTINGS: All patients received their treatment at the Swiss Paraplegic Centre in Nottwil, near Lucerne (Switzerland). METHODS: The samples were taken from the bladder fundus during endoscopic urologic operations. Histopathological standard procedures were carried out. Statistical analysis including Kruskal-Wallis and Chi-square tests were performed. RESULTS: Histopathological analysis showed abnormal alterations of the urinary bladder mucosa in 86 SCI-patients: (91.5%). 63 cases (67.0%) showed a chronic type and 23 cases (24.5%) showed a subacute type of inflammation. A normal urinary bladder was found in eight cases (8.5%). The three hypotheses were statistically not rejected. CONCLUSION: Results demonstrated no correlation between the number of bladder infections per year, the period since injury, the neurologic level of the spinal cord lesion and the histopathology of the urinary bladder mucosa.

Glial lesion of the infratemporal fossa presenting as a soft tissue middle ear mass - rudimentary encephalocele or neural crest remnant?

We report about ectopic glial tissue of the skull base and the parapharyngeal space presenting as a soft tissue mass in the middle ear. An 11-year-old boy presented with bilateral conductive hearing loss since early childhood. The history included previously removed lesions consistent with ectopic neuroglial tissue of the tongue and the parapharyngeal space soon after birth, as well as surgery for cleft palate. High resolution computed tomography of the petrous bone and magnetic resonance imaging were useful in identifying the skull base defect and in characterizing the lesion's relation to the brain. There was no clinical, radiological or surgical evidence of any associated dural defect. The lesion was removed via a modified infratemporal approach. Histology revealed neuroglial tissue with calcifications without any signs of mesodermal or entodermal origin. On the basis of this case the pathogenesis and diagnosis of ectopic brain tissue and its relation to the more commonly encountered meningoencephalic herniations are reviewed. Furthermore therapeutical implications are discussed.

[Angiosarcoma of the frontal sinus. Case report and review of the literature]. / Angiosarkom der Stirnhöhle. Fallbericht und Literaturübersicht.

Angiosarcomas are very rare but highly malignant soft tissue tumors derived from the vascular endothelium. The tumor is most commonly found in the skin. The cancer is known to cause early and widespread metastases leading to a very poor prognosis of less than 24 months. The therapy of choice is radical surgery followed by adjuvant radiation. In this case study, we report on a patient with a very unusual localization of angiosarcoma in the frontal sinus. Based on this case, we discuss important aspects of tumor biology, diagnostic procedures, and histologic features as well as therapeutic options. We conclude that angiosarcoma has to be considered by a differential diagnosis in all head and neck neoplasias with uncertain histology.

Correlation of imaging techniques to histopathology in patients with diabetic foot syndrome and clinical suspicion of chronic osteomyelitis. The role of high-resolution ultrasound.

OBJECTIVE: To investigate the role of ultrasound in the diagnosis of osteomyelitis in the diabetic foot compared with magnetic resonance imaging (MRI), bone scintigraphy (BS), and plain film radiography (PFR). RESEARCH DESIGN AND METHODS: We investigated 19 consecutive diabetic patients (2 women, 17 men, age 60.7 +/- 9.8 years, BMI 27.0 +/- 3.8 kg/m2) with clinical suspicion of bone infection of the foot. A high-resolution ultrasound system (Esaote/Biosound, Munich) with a linear array transducer up to 13.0 MHz was used. The prospective and blinded results of each method were compared with histopathology as the reference method after metatarsal resection. RESULTS: In 14 of 19 patients, histopathology confirmed osteomyelitis. Ultrasound showed a sensitivity of 79% (PFR, 69%; BS, 83%; MRI, 100%), a specificity of 80% (PFR, 80%; BS, 75%; MRI, 75%), a positive predictive value of 92% (PFR, 90%; BS, 91%; MRI, 93%), and a negative predictive value of 57% (PFR, 50%; BS, 60%; MRI, 100%). CONCLUSIONS: Our data indicate that ultrasound might have a better diagnostic power for detecting chronic osteomyelitis in the diabetic foot than PFR and has similar sensitivity and specificity as BS. MRI is superior to the other three methods. We conclude that the use of ultrasound in the management of the diabetic foot is worthy of further investigation.

Health status of pediatric refugees in Portland, ME.

BACKGROUND: An understanding of the health conditions affecting pediatric refugees is essential to providing responsible health care for them when they arrive in the United States. OBJECTIVE: To assess the health status of pediatric refugees in an area of increased refugee resettlement. DESIGN: Retrospective medical records review. SETTING: Ambulatory clinic at Maine Medical Center in Portland, a community and referral hospital. PATIENTS: One hundred thirty-two refugees and immigrants aged 2 months through 18 years who had initial health care evaluations during 1994 and 1995. RESULTS: Sixty-six patients arrived from Africa, 22 from the former Yugoslavia, and the remainder from the former Soviet Union, Middle Asia, Southeast Asia, and Latin America. The mean age of the patients was 10 years; 56 (42.4%) were female. The overall health status of most of the children was good, with most having appropriate weight and height for age. Dental caries and dermatologic conditions were the most prevalent findings on physical examination. Two patients had evidence of traumatic injuries. The results of tuberculin (Mantoux) tests were positive (> or =10 mm) in 45 (35.2%) of 128 children for whom results were noted, hepatitis B surface antigen was detected in 5 (4.0%) of 124 children, and hepatitis B surface antibody was detected in 26 (21.1%) of 123 children. Five (16.7%) of 30 children younger than 6 years had elevated blood lead levels; anemia was detected in 25 (19.7%) of 127 children with hematocrit results available. Stool specimens were obtained from 87 patients, of whom 38 (43.7%) had pathogenic parasites in at least 1 specimen. CONCLUSIONS: Pediatric refugees arrive in the United States with a variety of conditions that may be unfamiliar to practitioners trained in this country. The results of this study support the screening of refugees from Africa and other regions for tuberculosis, stool parasites, and hepatitis B.

[Subepidermal calcified nodule (calculus) of the eyelid]. / Subepidermaler kalzifizierter Knoten (Kalkulus) des Lides.

A 9-year-old boy presented with a painless hard tumor in the right lower lid. It had grown slowly since 12 months. Three months before presentation cryotherapy was administered by a dermatologist because of a presumed wart. Both eyes were normal. Clinical differential diagnosis included a keratoakanthoma and a wart. Excisional biopsy was performed. Histology revealed granular deposits which stained positive with hematoxylin-eosin and von Kossa stain. Though a secondary (dystrophic) calcinosis of the lid following cryotherapy could not be ruled out a diagnosis of an idiopathic subepidermal calcified nodule (calculus) of the lid was established.

[Focal mucinosis of the eyelid]. / Fokale Muzinose des Lides.

PURPOSE: To present a case of focal mucinosis of the eyelid. PATIENT: A male patient of Turkish origin born in 1982 desired therapy in 1995 for an asymptomatic tumour of the left medial upper lid which had been present probably since birth. The tumour was reduced with argon laser photocoagulation. Fourteen months later, in 1997, the tumour had enlarged so that a surgical excision was performed which histologically was interpreted as an unspecific inflammation. In 1998, the tumour had grown again at the original site, and there were additional three pedunculated tumours nearby at the lid margin. All tumours were surgically excised. Histology showed empty spaces in the upper dermis which contained some connective fibers, benign appearing fibroblasts and some leukocytes. The PAS-reaction and S100-immunohistology were negative while the lesion stained positive for alcianblue. The epidermis was intact. A diagnosis of a focal mucinosis of the eyelid was established. CONCLUSIONS: Focal mucinosis of the eyelid seems to be exceedingly rare. It is probably caused by a local overproduction of hyaluronic acid of unknown etiology. Our patient demonstrates that focal mucinosis might perhaps be congenital. Moreover it may recur if excision is not complete. Focal mucinosis should be included in the differential diagnosis of long-lasting, asymptomatic lid tumours.

[Metastatic eyelid tumors--description of clinical aspects and histology based on three cases]. / Metastatische Lidtumoren--Beschreibung von Klinik und Histologie anhand von drei exemplarischen Fällen.

Clinical findings and histology of secondary lid tumors are described by example of three cases. The rare lid metastases appear mainly in three different patterns. Except cytology, which depends on the primary tumor, their morphology is quite uniform. Lid metastases of a cutaneous melanoma, a contralateral uveal melanoma and, probably reported for the second time, a leiomyosarcoma are presented.

Isolated granulocytic sarcoma of the ovary: histologic, electron microscopic, and immunohistochemical findings.

An isolated granulocytic sarcoma (myelosarcoma) of the right ovary occurred in the absence of leukemia in a 49-year-old woman. The diagnosis of this tumor, which occurs extremely rarely in the ovary, was established by light microscopic, immunohistochemical, and electron microscopic investigations. The major cell population consisted of immature myeloid cells; scattered megakaryocytes were also seen. The tumor exhibited a prominent cellular stroma with scattered follicle-like collections of B-lymphocytes and many fibroblasts, giving the initial impression that the tumor could be of mesenchymal origin. Twelve months after operation, the patient still exhibits no evidence of leukemia.

Neuroepithelial adenocarcinoma of the eye.

A 29-year-old male patient with a microphthalmos on the right side since birth was seen in June 1987 in the University Eye Clinic because of a massive exophthalmus of the former microphthalmic eye. Computer tomography revealed a diffuse, infiltrating tumor of the right orbit. The bulbus was not demarcated, and the whole orbita had to be eviscerated. Histologically, we found a solid, undifferentiated tumor with clear signs of malignancy. It consisted of epithelial cells, partly in nest formation, which were keratin positive and vimentin negative, and of more spindle-shaped formations which were keratin negative and vimentin positive. In some areas, the tumor showed a tubular or an adenoid proliferation. CEA or S-100 could not be demonstrated. The histopathological diagnosis was neuroepithelial adenocarcinoma of the eye. The differential diagnosis and the genesis of the tumor are discussed.

Primary extraskeletal mesenchymal chondrosarcoma of the lid.

A 15-year-old girl presented with a painless nodule in the nasal lower-lid portion of the left eye at the beginning of 1989. The tumor was excised in March 1989, and the histopathologic diagnosis was - erroneously - a chondromatous choristoma of the lid. The tumor recurred within several weeks. Another excision was performed, which led to the diagnosis of a malignant mesenchymal chondrosarcoma of the lid. Histopathology revealed the typical bimorphic pattern, with well-differentiated chondrocytes being surrounded by small anaplastic cells. The tumor cells stained positive for S100-protein and vimentin, were negative for cytokeratin and were studied ultrastructurally. Radical excision and adjuvant chemotherapy were performed in our patient; at 18 months after the onset of tumor growth, she is free of local or general tumor recurrence. To our knowledge, primary mesenchymal chondrosarcoma has not previously been described in the lid area.

Long-term prognosis of focal sclerosing glomerulonephritis. An analysis of 250 cases with particular regard to tubulointerstitial changes.

The following results were obtained in a long-term retrospective study including 250 patients with focal sclerosing glomerulonephritis: 1. The renal survival rate (RSR) was 90% at 5 years and 67% at 10 years, the average period of observation being 4.7 years. 2. Univariate analysis revealed that the following morphologic and clinical parameters are associated with an increased risk of terminal renal failure or death due to renal causes: a) Tubulointerstitial changes in the form of interstitial fibrosis, with or without acute renal failure; b) Advanced glomerular lesions; c) Advanced vascular alterations; d) Nephrotic syndrome present at the time of the biopsy; e) Elevated serum creatinine concentration at the time of the biopsy; f) Arterial hypertension at the time of the biopsy; g) Greater age at diagnosis; h) Male sex. 3. Multivariate survivorship analysis showed that tubulointerstitial changes and the presence of nephrotic syndrome at the time of biopsy are the only variables with significant independent predictive value for the outcome. Assessment of these factors thus allows the pathologist to make a relevant statement concerning the probable course and prognosis of the disease at the time of the diagnostic biopsy.

IgA nephritis: on the importance of morphological and clinical parameters in the long-term prognosis of 239 patients.

This study is concerned with the correlation between tubulointerstitial changes (interstitial fibrosis, acute renal failure, and interstitial fibrosis with acute renal failure), glomerular changes (focal and segmental lesions, hyperperfusion lesions), vascular changes, clinical data at the time of biopsy (serum creatinine concentration, creatinine clearance, hematuria, proteinuria, and hypertension) and first symptoms (hematuria, proteinuria and hypertension) and the kidney survival rate in 239 patients with IgA nephritis without nephrotic syndrome. The morphological and clinical parameters were subjected to multivariate analysis in order to examine their significance with regard to the prognosis. The interstitial fibrosis was proven to be the most important morphological parameter, and the most important clinical parameters were the serum creatinine concentration and the creatinine clearance.

Acute renal failure in man: new aspects concerning pathogenesis. A morphometric study.

The morphometric investigation of the proximal and distal tubules, the cortical interstitium, the intertubular capillaries, the renal corpuscles and the juxtaglomerular apparatuses (JGAs) in 56 cases in the oligoanuric, polyuric, and normuric phases of human acute renal failure (ARF), 6 cases of myeloma kidney with clinically confirmed ARF and 21 control kidneys revealed the following: (1) The main pathological change in human ARF is swelling of the epithelial cells of the proximal and distal tubules. Necrosis of these cells was observed in some cases but usually only as single cell necroses. (2) The interstitium of the cortex and of the outer stripe of the outer medulla is significantly widened in most cases of ARF. (3) In proximal tubules proximal to occluding casts (which were observed only in the plasmacytoma cases), the lumina are not widened but are narrower than normal, and the cross-sectional area of the epithelium is not greater but smaller than normal. (4) The JGAs were significantly larger in kidneys in the oligoanuric phase of ARF (with 1 exception) than in normal kidneys. In the normuric and polyuric phases they were slightly (not significantly) smaller than normal. In myeloma kidneys with occluding casts and/or diffuse interstitial fibrosis, the JGAs were significantly smaller than normal. From these findings it is concluded that: (1) The fall in glomerular filtration rate (GFR) in the postshock phase of ARF is not caused by nonselective back-diffusion of the primary urine through necrotic tubules or by compression of the lumina of the proximal and distal tubules by interstitial edema. A fall in GFR associated with occluding casts in the distal tubules is found only in the myeloma kidney and does not lead to widening of the proximal tubules but to tubular atrophy and narrowing of the lumen. (2) The casts seen in the lumina of the ascending limb of Henle's loop in some cases of ARF, which consist of hemoglobin, Tamm-Horsfall protein or desquamated blebs, do not occlude the lumen, since they are not associated with atrophy or luminal dilatation of the proximal tubules. (3) The JGAs with their secretory product renin-angiotensin II, together with adenosine, which is released in kidneys with ischemic or toxic damage, play a critical role in the pathogenesis of ARF. (4) In myeloma kidneys with ARF, in which the JGAs are markedly atrophic, the potentiated effect of adenosine that has been observed with a chronic absence of urine flow probably leads to a progressive, irreversible drop in GFR associated with tubular atrophy.