Tumors of the bones of the feet: the clinicopathologic features of 150 cases.

The small bones of the feet may be affected by a full spectrum of benign and malignant processes. Essentially all tumors which may arise elsewhere in the skeletal system may also occur in the feet. Although investigators have completed exhaustive studies detailing the occurrence of tumors of the skeletal system at large, few series have adequately summarized such tumors as they occur in the small bones of the feet. A study was made of 150 consecutive cases of mass-forming tumors of the bones of the feet, which were diagnosed over a 15-year period at a major cancer center. This series confirms that the bones of the feet are affected by a full spectrum of mass-forming tumors; however, such lesions arise with an incidence that is unique to this site. The various tumors identified in this series are presented and the associated epidemiologic data are discussed. Unusual trends in incidence, apparently unique to this location, are stressed.

Lack of correlation of functional scintigraphy with (99m)technetium-methoxyisobutylisonitrile with histological necrosis following induction chemotherapy or measures of P-glycoprotein expression in high-grade osteosarcoma.

In osteosarcoma, some studies have suggested P-glycoprotein expression is a prognostic factor. The clearance of (99m)technetium hexakis-2-methoxyisobutylisonitrile ((99m)Tc-MIBI) has been used in some tumor systems as an in vivo measure of P-glycoprotein-mediated efflux. In this study we explored the correlation between (99m)Tc-MIBI clearance and histological necrosis following induction chemotherapy and P-glycoprotein expression in osteosarcoma. The primary tumors of 20 patients with high-grade osteosarcoma were imaged at diagnosis with (99m)Tc-MIBI, and the uptake ratios and biological half-lives were calculated. P-Glycoprotein expression in the tumor tissue was determined immunohistochemically and by measuring mRNA expression of the multidrug resistance-1 gene. The histological necrosis following induction chemotherapy was assessed by the Huvos grading system. The biological half-life of (99m)Tc-MIBI ranged from 1.4 to 52.5 h. Seven of the 20 tumor samples had a favorable extent of necrosis following induction chemotherapy. The (99m)Tc-MIBI half-life and uptake ratio showed no correlation with histological necrosis following induction chemotherapy. The (99m)Tc-MIBI half-life and uptake ratio did not correlate with either measure of P-glycoprotein expression. The results of this pilot study indicate that (99m)Tc-MIBI imaging is not an effective predictor of histological necrosis following induction chemotherapy in high-grade osteosarcoma. (99m)Tc-MIBI imaging did not correlate with measures of P-glycoprotein expression in the tumor tissue.

Expression of melanocytic differentiation markers in malignant melanomas of the oral and sinonasal mucosa.

Malignant melanomas of the oral and sinonasal mucosa are rare tumors. Amelanotic variants can, on occasion, be difficult to recognize by routine light microscopy. Immunohistochemical studies may be needed for a final diagnosis. A number of new monoclonal antibodies to melanocytic differentiation antigens have been studied recently on primary cutaneous and metastatic melanoma. However, little is known about these antibodies for the diagnosis of mucosal melanomas. In this study the authors analyzed 79 oral and sinonasal mucosal melanomas of 65 patients. A total of 35 tumors originated from the oral mucosa (21 primary tumors, eight local recurrences, and six metastases) and 44 melanomas were from the sinonasal tract (27 primary tumors, nine local recurrences, and eight metastases). Immunohistochemical studies were performed on paraffin-embedded tissues, using the following antibodies: anti-S-100 protein, T311 (anti-tyrosinase), A103 (anti-Mart-1/Melan-A), D5 (antimicrophthalmia-associated transcription factor), and HMB-45 (anti-gp100). Of 35 oral mucosal tumors, 34 (97%) were positive with anti-S-100 protein, 33 (94%) with T311, 30 (85%) with A103, 26 (74%) with D5, and 25 (71%) with HMB-45. All five desmoplastic melanomas of the oral mucosa were positive for S-100 protein, four for tyrosinase, and one each for HMB-45 and A103. No desmoplastic melanoma was positive with D5. All 44 sinonasal melanomas were positive for tyrosinase and Mart-1/Melan-A (100%). Forty-three (98%) were positive with HMB-45, 42 (95%) with anti-S-100 protein, and 40 (91%) with D5. These results reveal that T311 is the most sensitive marker for sinonasal melanomas and closely approaches the sensitivity of anti-S-100 protein for oral mucosal melanomas. For desmoplastic mucosal tumors, anti-S-100 protein remains the most sensitive marker.

Role of fine-needle aspiration biopsy and frozen section analysis in the surgical management of thyroid tumors.

INTRODUCTION: The role of fine-needle aspiration (FNA) and frozen section (FS) in the management of thyroid neoplasms continues to generate considerable controversy. We reviewed our recent experience to determine the clinical utility of FNA and FS in our surgical management and intraoperative decision-making. METHODS: All patients who had operations for thyroid disease between January 1996 and June 1999 were identified in our prospective database. Completion and incidental thyroidectomies were excluded. Data obtained from the pathology files included FNA, FS, and the final histologic diagnosis. RESULTS: Five hundred sixty-four patients, including 409 women (73%), with a median age of 50 years (range, 6-94) were identified, of whom 293 (52%) had cancer diagnosed on permanent sections. Three hundred twenty-nine patients (58%) had evaluable FNA, of which 91 (28%) were benign, 94 were malignant (28%), and 144 (44%) were suspicious (46% of these were malignant on final). Frozen section was performed in 397 (70%) patients; of these samples, 170 (43%) were found to be benign, 106 (27%) were malignant, and 121 (30%) were deferred (46% malignant on final). Fine-needle aspiration positively identified 51% of confirmed malignancies; 13% of patients with malignancy had a benign FNA result. Total thyroidectomy was performed in 64% of malignant tumors and 29% of benign thyroid disease (P < .001). Logistic regression revealed no association of extent of surgery with FNA results. A frozen section positive for malignancy was associated with total thyroidectomy (P < .001, RR 6 [CI 3-10]), and a negative frozen section report was associated with lobectomy (P < .05, RR 0.5 [CI 0.3-0.96]). Frozen sections results altered the preoperative plan in only 29 patients (5%). CONCLUSION: Results of preoperative FNA had no direct impact on the selection of the surgical procedure in this selected cohort. Intraoperative FS added very little to surgical management. The majority of thyroid operations at this institution are planned and performed based on known prognostic factors and intraoperative findings.

Basaloid squamous cell carcinoma of the head and neck.

OBJECTIVE/HYPOTHESIS: Basaloid squamous cell carcinoma (BSCC), an uncommon tumor with predilection for the upper aerodigestive tract, is a distinct variant of squamous carcinoma, because of its unique histological features and ominous clinical behavior. This study reviews the experience in treating BSCC from two institutions. STUDY DESIGN: Retrospective. METHODS: H&E-stained sections from 20 patients with BSCC of the head and neck were reviewed and clinical follow-up was obtained for all patients. RESULTS: The study group consisted of 14 male and 6 female patients. Their ages ranged from 43 to 85 years, with a mean age of 62 years. Sites of origin included the larynx (4), tongue (3), pyriform sinus (3), nose (2), floor of mouth (2), mastoid (1), tonsil (1), epiglottis (1), nasopharynx (1), trachea (1), and palate (1). Pain was the most common presenting symptom (5 cases), followed by hoarseness and bleeding (3 cases each). Tobacco and alcohol abuse was noted in 17 patients. Treatment modalities included surgery with or without chemotherapy or radiotherapy in 13 patients, chemotherapy with irradiation in 2, chemotherapy alone in 2, and radiotherapy alone in 3. Clinical follow-up revealed no evidence of disease in 11 patients. Four were alive with disease at the time of writing and five died of disease. CONCLUSION: BSCC is a highly aggressive malignant tumor that presents in elderly patients who have a history of abuse of tobacco or alcohol, or both. Greater number of patients must be studied and compared with age-matched and stage-matched controls of conventional squamous cell carcinoma to determine whether the poor clinical outcome is related more to high-stage presentation or to the tumor's high-grade malignant cytological features.

Prognostic impact of P53 status in Ewing sarcoma.

BACKGROUND: Disease stage at the time of diagnosis and response to therapy are the main prognostic factors for patients with Ewing sarcoma or peripheral neuroectodermal tumor (ES/PNET). The primary genetic alteration in ES/PNET, the fusion of the EWS gene with FLI1 or ERG, is diagnostically highly specific for these tumors, and molecular variation in the structure of the EWS-FLI1 fusion gene also is of prognostic significance. In contrast, secondary genetic alterations, such as P53 alterations, are relatively uncommon in ES/PNET, and their prognostic impact has not been extensively studied. METHODS: Prechemotherapy, paraffin embedded, nondecalcified, primary tumor material in a well-characterized series of 55 patients with ES/PNET with defined EWS-FLI1 fusion transcripts (32 patients with type 1 and 23 patients with other types) was studied retrospectively by immunohistochemical techniques for cell cycle regulators and proliferative markers, such as P53, P21(WAF1), and Ki-67, as well as by the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) technique for apoptosis. Nuclear P53 expression in > 20% of tumor cells was scored as aberrant overexpression. Histologic response to neoadjuvant chemotherapy was assessed. RESULTS: Aberrant P53 expression (in > 20% of tumor cells) was present in 6 patients (11%) but showed no statistically significant correlation with disease stage, tumor size, proliferation rate (Ki-67), apoptotic rate (TUNEL), or EWS-FLI1 fusion type. By univariate analysis, the P53 > 20% group showed a significantly poorer overall survival among patients with localized disease (n = 43 patients) (P = 0.001) and in the entire study group (P = 0.01). In multivariate Cox analyses of overall survival, P53 > 20% was the strongest negative factor among prognostic factors available at the time of diagnosis (P = 0.001; relative risk [RR] = 9) and when chemotherapy response was included in the analysis (P53 > 20%: P = 0.01; RR = 10). CONCLUSIONS: P53 alteration appears to define a small clinical subset of patients with ES/PNET with a markedly poor outcome. The current observations warrant a systematic prospective study with comprehensive P53 mutation analysis. [See related article on pages 793-9, this issue.]

Prognostic impact of INK4A deletion in Ewing sarcoma.

BACKGROUND: The primary genetic alteration in > 95% of Ewing sarcomas (ES) is a specific fusion of EWS with FLI1 or ERG. Secondary genetic alterations possibly involved in progression of ES are not well understood. A recent study found loss of the negative cell cycle regulator gene INK4A in 8 of 27 ES samples (30%). To confirm these findings and evaluate their prognostic significance, the authors studied INK4A deletion in 41 ES samples from 39 patients. METHODS: Using Southern blot analysis with an INK4A p16 cDNA probe, the intensity of the INK4A bands in ES DNA samples was normalized to that of a control probe and compared with nondeleted control DNA; > 50% signal reduction was scored as evidence of deletion. All ES tumor DNA samples previously were confirmed to have EWS rearrangements on the same Southern blots, using a cDNA probe spanning the EWS breakpoint region. RESULTS: Tumors from 7 patients (18%) showed INK4A deletion independent of disease stage (localized or metastatic) or sample source (primary tumor or metastasis). INK4A was a strong negative factor for disease specific survival in univariate analysis (P = 0.001) and in multivariate analysis including stage (relative risk = 6; P = 0.001). CONCLUSIONS: INK4A deletions appear to be the most frequent secondary molecular genetic alteration found to date in ES. Their possible clinical usefulness in identifying a subset of ES patients with poor prognosis merits systematic prospective analysis. [See related article on pages 783-92.]

Mutagen sensitivity and environmental exposures as contributing causes of chromosome 3p losses in head and neck cancers.

The interaction between environmental exposures and host susceptibility may lead to specific mutational events within head and neck squamous cell carcinoma (HNSCC). Furthermore, this interplay may determine not only the probability of cancer development but also the biologic characteristics of the tumor once it occurs. To better understand the relationship of mutagen sensitivity and tobacco and/or alcohol consumption on HNSCC carcinogenesis, we examined loss of heterozygosity on chromosome 3p in 58 HNSCCs using 10 microsatellite markers. Mutagen sensitivity was determined in vitro by quantitating bleomycin-induced chromatid breaks utilizing peripheral blood lympocytes from respective patients. Forty-six of the 58 invasive cancers showed allelic loss at one or more loci. Consistent with previous investigations, three discrete regions of deletions were identified: 3p13-14.2, 3p21.1-21. 2, and 3p25.1-26.1. The frequency and types of deletions were dependent upon tobacco and alcohol exposures. The distal region of 3p but not the remaining two regions was most frequently influenced by tobacco exposure. In contrast, heavy alcohol use when combined with tobacco use was associated with whole-arm loss of 3p rather than identifiable site-specific damage. Furthermore, this combined influence of alcohol and tobacco exposures on whole-arm loss was most apparent in those patients who expressed mutagen-sensitivity; the odds ratio of whole-arm loss increasing from 2.67 (95% CI 0. 21-33.49) in those individuals who were mutagen resistant to 13.5 (95% CI 1.3-136.0; P = 0.02 by Fisher's exact test) in those who were mutagen sensitive. An assessment of clinical parameters in this population demonstrated that patients with whole-arm loss were more likely to present with cervical lymph node metastases and advanced stage disease than patients with partial losses. Results indicate that various environmental exposures as well as the expression of mutagen sensitivity will influence the types of chromosome 3p allelic losses in head and neck cancers as well as the behavior of disease once it develops.

Myoepithelial carcinoma of the salivary glands: a clinicopathologic study of 25 patients.

Salivary gland carcinomas displaying exclusively myoepithelial differentiation (myoepithelial carcinoma) are considered rare. Their histopathologic features, immunohistochemical profile, and clinical behavior are not well characterized. The authors reviewed the clinicopathologic features of 25 salivary gland tumors fulfilling two fundamental histologic criteria: unequivocally malignant and exclusively myoepithelial. For most of these, the original diagnosis was malignant mixed tumor. Thirteen men and 12 women aged 24 to 77 years (mean age, 55 yrs) participated in the study, and most presented with a painless mass. The parotid gland was the most common site (n = 15). Tumors ranged from 2.1 to 5.5 cm, arising either in association with a benign mixed tumor (n = 15) or de novo (n = 10). Histologically, all the tumors displayed infiltrative growth and most had a characteristic multinodular architecture with a cellular periphery and central necrotic/myxoid zones. Epithelioid, hyaline, spindle, clear, or mixed cell types were noted with accompanying myxoid and/or hyalinized extracellular matrix. Ten tumors were high grade cytologically and 15 were low grade. The mitotic rate ranged from three to 51 mitoses per 10 high-power fields. Necrosis was present in 15 tumors and perineural and vascular invasion were identified in 11 and four neoplasms respectively. Immunoreactivities included CAM5.2 (89%), AE1:AE3 (100%), 34betaE12 (92%), cytokeratin 7 (21%), cytokeratin 14 (53%), vimentin (100%), S-100 protein (100%), smooth muscle actin (50%), calponin (75%), muscle-specific actin (31%), glial fibrillary acidic protein (31%), carcinoembryonic antigen (0%), and epithelial membrane antigen (21%). Ultrastructural examination of three tumors showed myoepithelial features. Ten patients developed recurrences, mostly multiple. Follow up of 17 patients showed that eight patients (47%) developed metastases (six high grade, two low grade) and five patients (29%) died of disease (four high grade, one low grade) after a mean of 32 months. Two patients were alive with disease (19 and 49 mos). Ten patients (59%) were without any evidence of disease after a mean of 42.2 months. Myoepithelial carcinomas exhibit a wide spectrum of cytomorphologic features and diverse clinical outcomes. As a result of their morphologic heterogeneity, they can be confused easily with many tumors. Myoepithelial carcinomas have been underrecognized in the past, primarily by being lumped under a broader category of "malignant mixed tumor." Awareness of their unique cytoarchitectural patterns and immunohistochemical profile is crucial for accurate identification.

Primary fibrosarcoma and malignant fibrous histiocytoma of bone--a comparative ultrastructural study: evidence of a spectrum of fibroblastic differentiation.

As primary bone fibrosarcoma (FS) and malignant fibrous histiocytoma (MFH) have similar clinical, radiographic, or survival manifestations, ultrastructural and immunohistochemical studies were undertaken to determine the differentiation pathways of constituent malignant cells. Twelve cases of primary intraosseous FS and MFH were selected for this ultrastructural comparative study and were analyzed for fibroblastic or modified fibroblastic differentiation. There were 4 FS cases and 8 MFH cases, of which 5 were storiform-pleomorphic, 2 were giant cell, and 1 was myxoid type. All FS consisted of spindle fibroblasts with a prominent rough endoplasmic reticulum and Golgi apparatus, variable amounts of vimentin intermediate filaments, and extracellular collagen fibrils. The MFH were composed of a mixture of spindle and pleomorphic fibroblasts (8/8), histiofibroblasts (4/8), and myofibroblasts (3/8). Variable numbers of undifferentiated cells were found in both tumors. In conclusion, fibroblastic differentiation and collagen production was noted in all cases. The often pleomorphic histiofibroblasts present in some MFH cases most likely represent "modified fibroblasts," similar to myofibroblasts. These findings support the hypothesis that the fibroblast and its variants are the predominant cell types found in these tumors, suggesting that the diagnostic entity MFH should be classified as a pleomorphic fibrosarcoma.

Osteosarcoma associated with absent thumbs: a report of two cases.

An 8-year-old Hispanic boy with a hypoplastic left thumb, absent right thumb, and short stature experienced right leg pain and limp. A right tibial lesion was imaged and found to be osteosarcoma on biopsy. A 6-year-old Hispanic girl with congenitally absent thumbs experienced a pathologic fracture of her left femur after a minor sports injury. The radiologic abnormality seen was diagnosed as osteosarcoma on biopsy. Both patients continue to do well after intensive preoperative and postoperative high-dose chemotherapy and definitive reconstructive limb surgery. Osteosarcoma has been linked to several congenital syndromes in which absent thumbs are a feature. These two patients with absent thumbs and no definable syndrome experiencing osteosarcoma suggest that congenitally absent thumbs might be a risk factor for osteosarcoma in the absence of a syndrome.

Cytokeratin immunoreactivity in Ewing's sarcoma: prevalence in 50 cases confirmed by molecular diagnostic studies.

Ewing's sarcoma (ES) and primitive neuroectodermal tumor (PNET) are characterized by the presence of the specific t(11;22)(q24;q12) or variants thereof, producing diagnostic EWS fusion transcripts. Cytokeratin has been reported sporadically to be expressed in some cases of ES/PNET. However, its prevalence has not been assessed systematically in a series of cases with confirmatory molecular or cytogenetic evidence of a diagnostic translocation. We present in detail three index patients in whom strong cytokeratin immunoreactivity was a confounding factor in the diagnosis. To establish further the prevalence of cytokeratin immunoreactivity in a series of well-characterized ES/PNET, we then performed immunohistochemical studies with antibodies CAM5.2 and AE1/AE3 on 50 cases of ES/PNET diagnosed at Memorial Sloan-Kettering Cancer Center in which molecular evidence of a specific ES/PNET-associated translocation were available. Immunoreactivity to cytokeratin was present in 10 cases (20%), in five diffusely and five focally. There was no significant association between cytokeratin expression and the following parameters: patient age, sex, skeletal and extraskeletal primary site, and the type of EWS fusion transcript. Cytokeratin expression, a manifestation of epithelial differentiation, is present in as many as 20% of ES/PNET in either a diffuse or focal pattern.

Association of EWS-FLI1 type 1 fusion with lower proliferative rate in Ewing's sarcoma.

The Ewing's sarcoma (ES) family of tumors, including peripheral neuroectodermal tumor (PNET), is defined genetically by specific chromosomal translocations resulting in fusion of the EWS gene with a member of the ETS family of transcription factors, either FLI1 (90-95%) or ERG (5-10%). A second level of molecular genetic heterogeneity stems from the variation in the location of the translocation breakpoints, resulting in the inclusion of different combinations of exons from EWS and FLI1 (or ERG) in the fusion products. The most common type of EWS-FLI1 fusion transcript, type 1, is associated with a favorable prognosis and appears to encode a functionally weaker transactivator, compared to other fusion types. We sought to determine whether the observed covariation of structure, function, and clinical course correlates with tumor cell kinetic parameters such as proliferative rate and apoptosis, and with expression of the receptor for insulin-like growth factor I (IGF-1R). In a group of 86 ES/PNET with defined EWS-ETS fusions (45 EWS-FLI1 type 1, 27 EWS-FLI1 non-type 1, 14 EWS-ERG), we assessed proliferation rate by immunostaining for Ki-67 using MIB1 antibody (n = 85), apoptosis by TUNEL assay (n = 66), and IGF-1R expression by immunostaining with antibody 1H7 (n = 78). Ki-67 proliferative index was lower in tumors with EWS-FLI1 type 1 than those with non-type 1 EWS-FLI1, whether analyzed as a continuous (P = 0.049) or categorical (P = 0.047) variable. Logistic regression analysis suggests that this association was secondary to the association of type 1 EWS-FLI1 and lower IGF-1R expression (P = 0.04). Comparing EWS-FLI1 to EWS-ERG cases, Ki-67 proliferative index was higher in the latter (P = 0.01, Mann-Whitney test; P = 0.02, Fisher's exact test), but there was no significant difference in IGF-1R. TUNEL results showed no significant differences between groups. Our results suggest that clinical and functional differences between alternative forms of EWS-FLI1 are paralleled by differences in proliferative rate, possibly mediated by differential regulation of the IGF-1R pathway.

Epstein-Barr virus in squamous carcinoma of the anterior nasal cavity.

Squamous carcinoma is the most common malignancy of the head and neck, but it rarely occurs in the nasal vestibule. Epstein-Barr virus (EBV) has been detected in and is causally linked to various head and neck tumors, particularly nasopharyngeal carcinoma. The possible role of EBV in squamous carcinoma of the anterior nasal cavity, particularly of the nasal vestibule, has not been previously investigated. Histologic sections from 17 patients with nasal vestibular squamous carcinoma were examined. Material for EBV detection by immunohistochemistry and by in situ hybridization was available in 15 of the 17 cases. The study group consisted of eight men and nine women ranging in age from 40 to 82 years (mean age, 64 years). None of the patients was of Asian descent. The squamous carcinomas were graded as well differentiated (one case), moderately differentiated (11 cases), and poorly differentiated (five cases). Fourteen patients were smokers; the history of smoking ranged from 20 to 60 pack-years. Treatment modalities included surgical resection, radiation, chemotherapy, or a combined approach. The clinical follow-up periods ranged from 7 months to 16 years. Three patients developed metastases, one of whom died of disease after 1 year. Epstein-Barr virus was not detected in any of the 15 of 17 cases tested by either immunohistochemistry or by in situ hybridization. Squamous carcinoma of the nasal vestibule is an uncommon cancer that is not causally related to EBV.

Low-grade osteogenic sarcoma arising in medullary and surface osseous locations.

Osteosarcomas represent a heterogeneous group of tumors with different histologic and clinical features, biologic behavior, and therapy. Histologic grading has remained the most important factor for predicting the clinical progression of osteosarcomas. Some of the most common diagnostic problems in surgical pathology related to low-grade osteogenic sarcoma are addressed.

Expression of HER2/erbB-2 correlates with survival in osteosarcoma.

PURPOSE: In osteosarcoma, prognostic factors at diagnosis other than clinical stage have not been clearly identified. The aim of this study was to determine whether human epidermal growth factor receptor 2 (HER2)/erbB-2, p-glycoprotein, or p53 expression correlated with histologic response to preoperative chemotherapy or event-free survival. PATIENTS AND METHODS: We performed a retrospective immunohistochemical study on material obtained from patients treated on the Memorial Sloan-Kettering Cancer Center T12 protocol between 1986 and 1993. Paraffin-embedded tissue was identified from 53 patients (73% of patients enrolled onto protocol) and stained for HER2/erbB-2, p53, and p-glycoprotein expression using standard monoclonal antibodies and methods. RESULTS: At the time of initial biopsy, 20 (42.6%) of 47 samples demonstrated high levels of HER2/erbB-2 expression. Higher frequencies of expression were observed in samples from patients with metastatic disease at presentation and at the time of relapse. Expression of HER2/erbB-2 correlated with a significantly worse histologic response (P =.03). In patients presenting with nonmetastatic disease, expression of HER2/erbB-2 at the time of initial biopsy was associated with a significantly decreased event-free survival (47% v 79% at 5 years, P =.05). p53 and p-glycoprotein expression did not correlate with histologic response or patient event-free survival. CONCLUSION: The correlation of HER2/erbB-2 expression with histologic response to preoperative chemotherapy and event-free survival in this study suggests that HER2/erbB-2 should be evaluated prospectively as a prognostic indicator. The correlation also suggests that clinical trials of antibodies that target this receptor, such as recombinant humanized anti-HER2 monoclonal antibody (Herceptin; Genentech, San Francisco, CA), should be considered for the treatment of osteosarcoma.

Epithelial tumors of the lacrimal glands: a clinicopathologic study.

We report the clinicopathologic features of epithelial tumors of the lacrimal gland apparatus, which are rare and therefore represent a major challenge for diagnosis and treatment. Histologic material from 22 lesions was studied by light microscopy, histochemistry, and immunohistochemistry. A comparison with major and minor salivary gland tumors was performed to analyze the relative distribution of these tumors and to establish whether salivary glands and lacrimal gland tumors are similar or different in their pathologic appearance and clinical behavior. There were three benign pleomorphic adenomas and 19 malignant tumors. The gender distribution was equal. The ages of the patients ranged from 10 to 73 years (mean age, 46 years). Among the malignant tumors, adenoid cystic carcinoma was the most common (nine cases), followed by mucoepidermoid carcinoma (three cases). There were two cases each of malignant mixed tumor and adenocarcinoma. All mucoepidermoid carcinomas and the adenocarcinomas were histologically high grade. There also was one case each of salivary duct carcinoma, spindle cell carcinoma, and oncocytic adenocarcinoma. Of 14 patients in whom clinical follow-up was available, seven had distant metastases and four died of their disease. The only case occurring in a child was an adenoid cystic carcinoma that recurred locally after 14 years. The clinical and pathologic features of lacrimal gland tumors resemble those lesions that arise in the intraoral minor salivary glands. The greater relative proportion of malignant cases in this series probably reflects a selection bias.

Henry L. Jaffe, MD (1896-1979), a pioneering authority on bone diseases: reflections and an appreciation.

The almost forgotton American pioneer in the history of bone pathology Henry L. Jaffe, MD died 20 years ago. He was instrumental in first describing many pathologic osseous conditions, both neoplastic and non-tumorous. His scientific achievement qualifies Dr Jaffe as a true giant of bont pathology.

Primary and secondary malignancies of the sternum.

Resection of the sternum can be performed safely and offers the best choice for cure for a primary sternal malignancy. Survival after resection is dependent on the histology and grade of the tumor.

Oncocytic and oncocytoid tumors of the salivary glands.

Primary pink cell tumors of the salivary glands constitute a heterogeneous group of benign and malignant lesions characterized by tumor cells with abundant eosinophilic cytoplasm. These tumors are composed predominantly of oncocytic, epidermoid, or myoepithelial cells. Tumors with a significant oncocytic component include Warthin's tumor, oncocytoma, and oncocytic carcinoma. An epidermoid component can be seen as a metaplastic change or as a true cellular constituent of a mucoepidermoid carcinoma. Myoepithelial cells may have an epithelioid character and as a consequence may impart a pink cell appearance in pleomorphic adenoma, myoepithelioma, and myoepithelial carcinoma. Usually most of these tumors are fairly distinct morphologically and do not present diagnostic dilemmas. In select circumstances, especially when dealing with a limited tissue sample, a systematic approach with an appropriate immunohistochemical panel should be used in order to arrive at a correct diagnosis. Accurate assessment is the key in the subsequent management and follow-up of these patients.