Expression of EGFR, HER-2/neu and KIT in germ cell tumours

BACKGROUND: Germ cell tumours (GCTs) represent an extraordinarily chemosensitive malignancy. However, 20-30% of patients with advanced disease cannot be cured by currently available treatments. The role of tyrosine kinase receptors has been widely studied in other malignancies. Yet, limited information is available on GCTs. METHODS: One hundred and nine paraffin-embedded GCTs in 84 patients were assessed by immunohistochemistry for epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER-2)/neu and KIT (CD117) expression. Univariate and multivariate analyses were performed to evaluate their role as predictive and/or prognostic factors. RESULTS: EGFR and HER-2/neu staining was detected in 28% and 13% of tumours, respectively, predominantly in nonseminomatous GCTs. KIT protein was almost universally expressed in seminomas (97%), being virtually absent in choriocarcinoma and teratocarcinoma subtypes. EGFR expression showed inverse association with tumour response of borderline significance. With a median follow-up of 10.6 years, no significant association was observed between the expression of any of these markers and relapse-free or overall survival. CONCLUSIONS: EGFR, HER-2/neu and KIT have differential patterns of expression in GCTs according to histological subtypes. The expression of these markers in our series had no prognostic or predictive significance (AU)

Pre-treatment serum lactate dehydrogenase level is an important prognostic factor in high-grade extremity osteosarcoma

BACKGROUND: Treatment of high-grade osteosarcoma remains a challenge. The prognostic significance of the pre-treatment serum lactate dehydrogenase (LDH) level is currently controversial. PATIENTS AND METHODS: We reviewed records from all patients diagnosed with conventional high-grade osteosarcoma at our institution over a 25-year period and analysed the prognostic significance of LDH in high-grade localised extremity osteosarcomas treated with chemotherapy. RESULTS: Between June 1977 and March 2003, 66 patients for whom follow-up was available were diagnosed with localised high-grade extremity osteosarcoma and treated with chemotherapy. The median age was 15 years, with only 3% older than 40 years, and the median follow-up was 100 months. The median progression-free survival (PFS) was 67 months and the median overall survival (OS) was 113 months. The absence of a response to chemotherapy was correlated with a trend toward lower PFS and OS. High serum pre-treatment LDH level was associated in multivariate analyses with a poorer prognosis for both PFS (HR=8.623, 95%CI: 1.71-43.37; p=0.009) and for OS (HR=9.38; 95%CI: 1.73-50.74; p=0.009). CONCLUSION: In this series, the pre-treatment serum LDH level had an independent prognostic value for both PFS and OS in patients with high-grade localised extremity osteosarcoma. This measurement should be included in a large prospective prognostic series (AU)

Absence of allelic imbalance involving EMSY, CAPN5, and PAK1 genes in papillary thyroid carcinoma.

Papillary thyroid cancer (PTC) accounts for 80% of all thyroid malignancies, and genetic alterations associated to its etiology remain largely unknown. Chromosomal band 11q13 seems to be one of the most frequently amplified regions in human cancer, providing several candidate genes that need detailed characterization. The aim of our study was to investigate the existence of allelic imbalance at EMSY, CAPN5, and PAK1, as candidate genes within 11q13.5-q14 region using a single nucleotide polymorphism-based analysis. We selected a panel of 9 polymorphisms that were analyzed in 41 thyroid carcinoma samples, their contralateral non-pathological tissue and 178 controls from the general population. We did not detect allelic imbalance at these loci in our series. However, we observed a difference in the EMSY-haplotype distribution among PTC patients when compared to controls (odds ratio=2.00; p=0.02). We conclude that 11q13.5-q14 is not imbalanced in PTC, but there is evidence suggesting that EMSY might be of relevance in PTC etiology.

Coexistence of two rare sarcomas: primary leiomyosarcoma of bone and epithelioid hemangioendothelioma of the liver.

A 33-year-old woman sought medical attention for a painful swelling of the left ankle. Plain radiographs revealed an osteolytic lesion involving the left distal tibia. An excisional biopsy provided the diagnosis of leiomyosarcoma in the tibia. A staging work-up was performed and an abdominal CT showed 4 liver hypodense lesions in both lobes with peripheral contrast enhancement. A liver biopsy confirmed the diagnosis of epithelioid hemangioendothelioma of the liver. No association between these two entities has been described before. This case introduces the importance of the pathological confirmation of apparent metastatic lesions in low grade sarcomas and provides a review of the literature of both tumours.

[Tuberculosis in the autopsy. Clinical and pathological study: an analysis of 92 cases of active tuberculosis found in 2,180 autopsies]. / Tuberculosis en la autopsia. Estudio anatomoclínico: análisis de 92 casos encontrados entre 2.180 autopsias.

BACKGROUND AND OBJECTIVE: Tuberculosis is an infectious disease currently having great importance in the daily clinical practice in Spain. Some cases of active tuberculosis are not identified until after the patient had died and an autopsy has been performed. This study has analyzed the clinical and pathological characteristics of patients diagnosed with active tuberculosis in the autopsy. MATERIAL AND METHOD: We reviewed all the autopsies performed in the University Hospital 12 de Octubre of Madrid between 1974 and 2002. The autopsy reports and clinical records were examined in those cases in which active tuberculosis was found. RESULTS: We found 92 cases of active tuberculosis, 57% corresponding to men. Mean age of this group was 64 years. A total of 20% of the patients died within 48 hours after admission. Predisposing factors were identified in 90% of the cases. Dyspnea (24% of cases) and wasting syndrome (23%) were the main symptoms that motivated patients to request medical attention. Up to 30% of cases had normal chest X-ray. Tuberculosis was suspected in only 46% of patients before death. Principal cause of death was tuberculosis in 61% of patients, 52% of patients had pulmonary tuberculosis, 28% suffered from miliary tuberculosis and 20% from extra-pulmonary tuberculosis. The lungs were the most frequently affected organ. Epithelioid granulomas were found in all patients. CONCLUSIONS: Tuberculosis is an uncommon finding in the autopsy as the cause of death. The presence of unspecific symptomatology, insufficient cost-effectiveness of the diagnostic tests and precocious death, are identified as the most frequent causes of undiagnosed tuberculosis.

Giant cell reparative granuloma of the occipital bone.

Giant cell reparative granuloma (GCRG) is a non-neoplastic fibrous lesion with unevenly distributed multinucleated giant cells, areas of osseous metaplasia and hemorrhage. The small bones of the hands and feet are the most common sites, followed by the vertebral bodies and craniofacial bones. In the craniofacial bones GCRG has been reported in the temporal bone, in the frontal bone and paranasal sinus. However, to the best of our knowledge no case has been reported in the occipital bone. We report on the imaging findings and pathological features of a GCRG of the occipital bone and discuss the differential diagnosis of this entity in this particular location, especially with giant cell tumor because of the therapeutic and prognostic implications.

Chest wall hamartoma. Report of two cases with secondary aneurysmal bone cysts.

Chest wall hamartoma is a rare non-neoplastic benign lesion occurring in the neonatal period with particular clinical, radiological and pathological features. Histologically, it is composed of a mixture of bone trabeculae with spindle-cell stroma, chondroblast-like cells, and mature and immature hyaline cartilage. Aneurysmal bone cyst is a benign lesion that may arise secondary to several bone processes, such as giant cell tumor, chondrosarcoma, non-ossifying fibroma or osteosarcoma. We present two new cases of chest wall hamartoma with secondary aneurysmatic bone cyst formation studied with histological and immunocytochemical methods.

Primary angioleiomyoma of the iliac bone: clinical pathological study of one case with flow cytometric DNA content and S-phase fraction analysis.

We report on a primary angioleiomyoma of the right iliac bone in a 28-year-old woman. To our knowledge this is the 16th reported case of a primary leiomyoma of bone, the 9th reported primary osseous angioleiomyoma and the first description of a primary angioleiomyoma located in the iliac bone. The problems of differentiating primary leiomyoma of bone from primary or metastatic leiomyosarcoma of bone are stressed. A literature review of primary leiomyomas of bone is presented.

[Branchial cysts with heterotopic salivary tissue in the upper third of the neck]. / Quistes branquiales con tejido salival heterotópico en el tercio superior del cuello.

The presence of heterotopic salivary gland tissue (HSGT) in rather uncommon in the neck. Usually it has been located in its lower third. HSGT in the upper neck is believed to be a rare entity. Two cases of HSGT in the upper neck are presented, with a review of their clinical and histopathological characteristics. The embryologic derivation of salivary tissue and close association with the branchial apparatus are discussed. The possibility of neoplastic transformation must always be considered in these uncommon lesions.

Immunoreactivity in granular cell tumours of the larynx.

OBJECTIVE: To elucidate histogenesis and behaviour of laryngeal granular cell tumours (GCT) and to determine the role of p53 protein expression in these lesions. METHODS: The clinical, pathological and immunohistochemical findings of three cases of laryngeal GCTs are described. RESULTS: All tumours were surgically excised and appeared histologically benign. Pseudoepitheliomatous hyperplasia, mitosis and nuclear pleomorphism were not found in any of the three cases. All lesions were negative for keratin 8, desmin and actin. Only one case stained for collagen IV. Positive staining was found for S-100 protein and CD68 in all tumours. Ki-67 and Bcl-2 staining was confined to occasional cells. p53 reactivity was seen in all tumours; positivity ranged from 35 to 42%. The three patients have remained free of disease without complications up to 10 years after treatment. CONCLUSION: Immunohistochemical findings support benign behaviour and a Schwann cell origin for laryngeal GCT. The expression of p53 by granular cells is unclear but appears to be unrelated to behaviour.

[Granular cell tumor: an infrequent cause of dysphonia in childhood]. / Tumor de células granulares: una causa poco frecuente de disfonía en la infancia.

Granular cell tumors (GCT) are rare and usually benign tumors whose histogenesis is debated. The skin, subcutaneous tissues, and mucosae of the head and neck are areas of predilection for GCT. Laryngeal involvement is uncommon, but may create diagnostic and therapeutic problems when it occurs. Laryngeal GCT are decidedly uncommon in children, only 17 cases having been reported in the literature. A case of GCT of the larynx in an 11-year-old girl is reported. The presenting symptom was hoarseness. The macroscopic tumor and hoarseness disappeared after chemotherapy (EVAIA) for Ewing sarcoma of the knee.

Detection of high mobility group I HMGI(Y) protein in the diagnosis of thyroid tumors: HMGI(Y) expression represents a potential diagnostic indicator of carcinoma.

Hyperplastic or neoplastic proliferative lesions of thyroid follicular epithelium consist of a spectrum, ranging from nodular hyperplasia to undifferentiated (anaplastic) carcinoma, and usually present as palpable thyroid nodules. Thyroid nodules are a common occurrence in the general population, but only a small proportion of them are eventually diagnosed as carcinoma. The difficulty in objectively identifying those thyroid nodules that are malignant to avoid unnecessary surgery, combined with the range and effectiveness of the available therapeutic options in those patients who do, indeed, have thyroid carcinoma, has prompted the search for tumor markers and prognostic indicators. The high mobility group I (HMGI) proteins represent a class of nuclear proteins involved in the regulation of chromatin structure and function. HMGI(Y), one of the members of this class, is expressed at high levels during embryogenesis and in malignant tumors but at generally low levels in normal adult human tissues. Previous work on a limited number of thyroid samples suggested that the detection of the HMGI(Y) proteins may provide a clinically useful diagnostic tool. To verify this assumption, we analyzed HMGI(Y) expression by a combination of immunohistochemistry and reverse transcription-PCR in 358 thyroid tissue samples that were representative of the spectrum of thyroid tumor pathology. HMGI(Y) was detectable in 18 of 19 follicular carcinomas, 92 of 96 papillary carcinomas, and 11 of 11 undifferentiated (anaplastic) carcinomas but in only 1 of 20 hyperplastic nodules, 44 of 200 follicular adenomas, and 0 of 12 normal tissue samples. The correlation between HMGI(Y) expression and a diagnosis of carcinoma was highly significant (P < 0.0001). We also prospectively collected and analyzed for HMGI(Y) expression by immunohistochemistry and reverse transcription-PCR in 12 fine needle aspiration biopsies from 10 patients who subsequently underwent surgical removal of a solitary thyroid nodule. HMGI(Y) was detectable only in the four fine needle aspiration biopsies, corresponding to the thyroid nodules that were definitively diagnosed as carcinomas after surgery (two follicular carcinomas and two papillary carcinomas). The remaining eight samples (six follicular adenomas and two samples consisting of normal follicular cells) were negative. The findings of this study confirm the differential expression of HMGI(Y) in thyroid neoplasia and indicate the HMGI(Y) protein as a potential marker for thyroid carcinoma.

Salivary gland heterotopia in the lower neck: a report of five cases.

Heterotopic salivary gland tissue (HSGT) represents an uncommon lesion, usually presenting as a discharging sinus in the base of the neck. Diagnostic criteria and embryogenesis of this entity still remain unclear. For the purpose of clarifying both subjects, all lateral cervical anomalies undergoing surgery during a 12-year period were examined. Histological study showed salivary tissue in 10 out of 119 patients. However, only 5 of them accomplished HSGT criteria. This study presents the second largest series to date of undisputed HSGT in the lower neck. Both accessory glands and branchial cleft anomalies should be distinguished from this lesion. Neoplastic transformation in HSGT, although extremely rare, should also be considered.

Nasolabial cyst: report of a case with extensive apocrine change.

The nasolabial cyst is a rare condition of the midline with an uncertain pathogenesis. This case report describes a 44-year-old woman in which the clinicopathologic findings were consistent with nasolabial cyst. On histologic examination, extensive apocrine change was noticed. To our knowledge, this feature has not been mentioned in previous papers. In addition, cases reported during the last decade are summarized.

[An analysis of the prognostic factors in renal-cell carcinoma]. / Analisis de factores pronósticos en el carcinoma de células renales.

OBJECTIVES: The study proposes the analysis of the influence of gross, microscopical and clinical pathoanatomical prognostic factors in the survival of patients with RCC through univariance and multivariance statistical analysis, and its global evaluation as a predictive model. PATIENTS AND METHOD: The study involved 218 RCC cases operated on over 20 years, with a mean follow-up of 60 months. RESULTS AND CONCLUSIONS: All prognostic factors studied have a significant influence on the survival. When studied jointly, they include separately and in order of significance the metastatic involvement, mitotic index, cava vein involvement, nuclear grade and sarcomatoid histologic pattern. Also, we confirm that considered jointly they conform a valid predictive model.

[Primary nasal sinus malignant melanomas]. / Melanomas malignos primarios nasosinusales.

Primary malignant melanoma of the mucosa of the nasal and paranasal sinuses is rare, difficult to treat, and usually has a poor prognosis. Seven cases, six women and one man (mean age 76.5 years), were treated at the Hospital 12 de Octubre (Madrid, Spain) during the period 1982-1994. The presenting symptoms, diagnostic evaluation, morphology, therapeutic modalities, histological evaluation, and clinical course were reviewed. Three patients were treated surgically and three received palliative irradiation. All had local recurrence or distant metasfases within 15 months after concluding treatment. The seventh patient refused treatment.

Juxtacortical chondromyxoid fibroma: imaging findings in three cases and a review of the literature.

Chondromyxoid fibroma is a rare bone neoplasm characterized by chondral, myxoid and fibrous differentiation. Uncommon locations include the bone surface. Roentgenography, MRI and ultrasound can suggest the diagnosis. However, diagnosis of chondromyxoid fibroma is rarely made prior to biopsy. We present the radiologic and pathologic findings in three patients with this tumor and a review of the literature.

[Response of cartilaginous neoplasms of the larynx to surgery and alternative therapies]. / Comportamiento de las neoplasias cartilaginosas de la laringe frente al tratamiento quirúrgico y las terapéuticas alternativas.

Three primary cartilaginous tumors of the larynx are reported: two chondrosarcomas (including an undifferentiated chondrosarcoma with prolonged survival) and one chondroma. The need for accurate histological staging, only possible after surgery, is emphasized. Surgery is teh preferred initial treatment.