Search

Rhabdomyosarcoma is a relatively common soft tissue sarcoma that frequently affects children and adolescents and may involve the head and neck. Rhabdomyosarcoma is defined by skeletal muscle differentiation which can be suggested by routine histology and confirmed by immunohistochemistry for the skeletal muscle-specific markers myogenin or myoD1. At the same time, it must be remembered that when it comes to head and neck malignancies, skeletal muscle differentiation is not limited to rhabdomyosarcoma. A lack of awareness of this phenomenon could lead to misdiagnosis and, subsequently, inappropriate therapeutic interventions. This review focuses on malignant neoplasms of the head and neck other than rhabdomyosarcoma that may exhibit rhabdomyoblastic differentiation, with an emphasis on strategies to resolve the diagnostic dilemmas these tumors may present. Axiomatically, no primary central nervous system tumors will be discussed.

Head and neck squamous cell carcinoma (HNSCC) is a common malignancy that continues to be difficult to treat and cure. In many organ systems and tumor types, there have been significant advances in the understanding of the molecular basis for tumorigenesis, disease progression and genetic implications for therapeutics. Although tumorigenesis pathways and the molecular etiologies of HNSCC have been extensively studied, there are still very few diagnostic clinical applications used in practice today. This review discusses current clinically applicable molecular markers, including viral detection of Epstein-Barr virus and human papillomavirus, and molecular targets that are used in diagnosis and management of HNSCC. The common oncogenes EGFR, RAS, CCND1, BRAF, and PIK3CA and tumor suppressor genes p53, CDKN2A and NOTCH are discussed for their associations with HNSCC. Discussion of markers with potential future applications is also included, with a focus on molecular alterations associated with targeted therapy resistance.

Adequate resection margins are critical to the treatment decisions and prognosis of patients with head and neck squamous cell carcinoma (HNSCC). However, there are numerous controversies regarding reporting and interpretation of the status of resection margins. Fundamental issues relating to the basic definition of margin adequacy, uniform reporting standards for margins, optimal method of specimen dissection, and the role of intraoperative frozen section evaluation, all require further clarification and standardization. Future horizons for margin surveillance offer the possible use of novel methods such as "molecular margins" and contact microscopic endoscopy, However, the limitations of these approaches need to be understood. The goal of this review was to evaluate these issues to define a more rational, standardized approach for achieving resection margin adequacy for patients with HNSCC undergoing curative resection., (Copyright © 2012 Wiley Periodicals, Inc.)

Although uncommon, cancer of an unknown primary (CUP) metastatic to cervical lymph nodes poses a range of dilemmas relating to optimal treatment. The ideal resolution would be a properly designed prospective randomized trial, but it is unlikely that this will ever be conducted in this group of patients. Accordingly, knowledge gained from retrospective studies and experience from treating patients with known head and neck primary tumors form the basis of therapeutic strategies in CUP. This review provides a critical appraisal of various treatment approaches described in the literature. Emerging treatment options for CUP with metastases to cervical lymph nodes are discussed in view of recent innovations in the field of head and neck oncology and suitable therapeutic strategies for particular clinical scenarios are presented. For pN1 or cN1 disease without extracapsular extension (ECE), selective neck dissection or radiotherapy offer high rates of regional control. For more advanced neck disease, intensive combined treatment is required, either a combination of neck dissection and radiotherapy, or initial (chemo)radiotherapy followed by neck dissection if a complete response is not recorded on imaging. Each of these approaches seems to be equally effective. Use of extensive bilateral neck/mucosal irradiation must be weighed against toxicity, availability of close follow-up with elective neck imaging and guided fine-needle aspiration biopsy (FNAB) when appropriate, the human papillomavirus (HPV) status of the tumor, and particularly against the distribution pattern (oropharynx in the majority of cases) and the emergence rate of hidden primary lesions (<10% after comprehensive workup). The addition of systemic agents is expected to yield similar improvement in outcome as has been observed for known head and neck primary tumors., (Copyright © 2011 Wiley Periodicals, Inc.)

In an era of advanced diagnostics, metastasis to cervical lymph nodes from an occult primary tumor is a rare clinical entity and accounts for approximately 3% of head and neck malignancies. Histologically, two thirds of cases are squamous cell carcinomas (SCCs), with other tissue types less common in the neck. With modern imaging and tissue examinations, a primary tumor initially undetected on physical examination is revealed in >50% of patients and the site of the index primary can be predicted with a high level of probability. In the present review, the range and limitations of diagnostic procedures are summarized and the optimal diagnostic workup is proposed. Initial preferred diagnostic procedures are a fine-needle aspiration biopsy (FNAB) and imaging. This allows directed surgical biopsy (such as tonsillectomy), based on the preliminary findings, and prevents misinterpretation of postsurgical images. When no primary lesion is suggested after imaging and panendoscopy, and for patients without a history of smoking and alcohol abuse, molecular profiling of an FNAB sample for human papillomavirus (HPV) and/or Epstein-Barr virus (EBV) is important., (Copyright © 2011 Wiley Periodicals, Inc.)

Large cell neuroendocrine carcinoma is a poorly differentiated neuroendocrine carcinoma that usually occurs in the lung. Although rare in the head and neck, salivary and mucosal subtypes are recognized. This article describes their characteristic light microscopic and immunohistochemical features and highlights the importance of accurate diagnosis, management and prognostic implications., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

This paper provides a review of the more common tumors to metastasize to 12 anatomic subsites of the head and neck, exclusive of cervical lymph nodes. Emphasis is placed on clinical rather than subclinical metastases discovered at autopsy.

We present a case of a parapharyngeal space myxoid liposarcoma. This case highlights the importance of wide surgical resection margins, and the difficult histological diagnosis.

Objective: To determine if perineural invasion (PNI) of small nerves affects the outcome of patients with squamous cell carcinoma (SCC) of the upper aerodigestive tract., Design: Retrospective clinicopathological study of patients with at least 2 years of follow-up and with negative margins and no prior, synchronous, or metachronous SCC., Setting: Academic otolaryngology department., Patients: One hundred forty-two patients who had SCC of the oral cavity, oropharynx and hypopharynx, or larynx resected between 1981 and 1991., Intervention: Surgery with or without adjuvant therapy., Main Outcome Measures: Local recurrence was examined with respect to PNI, nerve diameter, and microvascular or microlymphatic invasion. Perineural invasion was correlated with lymph node metastasis, extracapsular spread, and survival., Results: Perineural invasion of nerves less than 1 mm in diameter was present in 74 patients, lymphatic invasion in 53, and vascular invasion in 9. Perineural invasion was significantly associated with local recurrence (23% for PNI vs 9% for no PNI; P=. 02), and disease-specific mortality (54% mortality for PNI vs 25% for no PNI; P<.001). With extralaryngeal tumors, PNI was associated with nodal metastasis (73% vs 46%; P=.03). Perineural invasion was not associated with extracapsular spread (P=.47). Microvascular invasion, lymphatic invasion, and nerve diameter were not significantly related to local recurrence., Conclusions: Perineural invasion of small nerves is associated with an increased risk of local recurrence and cervical metastasis and is, independent of extracapsular spread, a predictor of survival for patients with SCC of the upper aerodigestive tract.

Basaloid squamous cell carcinoma is a recently recognized variant of squamous cell carcinoma. The lesion is histologically distinctive and manifests a predilection for the supraglottis, pyriform sinus, and tongue base. The immunohistochemical profile is discussed. The differential diagnoses include adenoid cystic carcinoma, small cell neuroendocrine carcinoma, basal cell adenocarcinoma, adenosquamous carcinoma, squamous cell carcinoma, spindle cell squamous carcinoma, mucoepidermoid carcinoma, and adenoid squamous cell carcinoma. Basaloid squamous cell carcinoma is a biologically high-grade tumor with a propensity for nodal as well as systemic metastases. It is a morphologic and phenotypic entity with a separate prognostic significance.

We describe two cases of basaloid squamous cell carcinoma of the head and neck with a spindle cell component. One tumor arose from the tonsil and the other in the larynx. Of the 30 cases of basaloid squamous cell carcinoma seen at this medical center, only 2 (6.6%) have demonstrated this histologic feature. To our knowledge, scant information exists with regards to a prominent spindle cell component occurring in basaloid squamous cell carcinoma, and none has been officially documented.

Introduction: We describe the clinicopathologic and flow cytometric features of 10 cases of basaloid squamous cell carcinoma (BSCC) of the head and neck to determine if DNA ploidy is a useful prognostic indicator. We also provide a review of 80 cases previously reported in the English language literature., Materials and Methods: The 10 cases were obtained from the surgical pathology files of Presbyterian University Hospital and The Eye and Ear Institute, Pittsburgh, PA (1987-1991). In all 10 cases, the microscopic slides and clinical data were reviewed. Flow cytometry was performed using the Hedley technique and formalin-fixed, paraffin-embedded tissue., Results: The mean age of patients with BSCC was 64 years (range, 49 to 75 years). Tumor involved the base of tongue (n = 5), hypopharynx-epiglottis (n = 3), and tonsil (n = 1). One case presented with cervical lymph node metastasis from an unknown primary site. Histologically, BSCC showed a biphasic pattern with basaloid-squamous elements, comedonecrosis, stromal hyalinization, surface dysplasia, and an in situ and/or invasive squamous cell carcinoma component. Flow cytometry revealed six diploid and four aneuploid tumors. Five of six patients with diploid and all four patients with aneuploid tumors developed early regional and/or distant metastases. Of the two patients who died of disease, one had a diploid and the other an aneuploid tumor., Conclusion: Our study reaffirms the predilection of BSCC for the base of tongue, pyriform sinus, and supraglottic larynx, and its aggressive biologic behavior with a high incidence of cervical lymph node metastasis (64%), distant spread (44%), and death from disease (38% mortality at 17 months median follow-up). However, in contrast to previous reports, tumor ploidy by flow cytometry provided no additional prognostic information beyond that supplied by routine histologic evaluation.

This paper describes the pathobiology of some of the more common skull base tumors. In addition to clinicopathologic features, emphasis is placed upon methods of diagnosis utilizing immunoperoxidase stains and molecular markers that may or may not impact upon prognosis.

Interleukin 2 (IL2) was injected peritumorally and intranodally in 36 patients with unresectable squamous cell carcinoma of the head and neck enrolled in an Eastern Cooperative Oncology Group-sponsored phase Ib trial (EST P-Z388). Groups of 6 patients received escalating doses(200, 2 x 10(3), 2 x 10(4), 2 x 10(5), 2 x 10(6), and 4 x 10(6) units) of IL2 daily 5 times/week for 2 weeks. Tumor biopsies were obtained before and after IL2 therapy. Tumor tissue was provided for histology, and the remaining fresh tissue was divided for snap-freezing in -75 degrees C and for separation of tumor-infiltrating lymphocytes (TIL) and tumor cells. Immunophenotyping of TIL performed on cryostat sections of paired pre- and post-IL2 biopsy tissues showed increases after IL2 therapy in the number of T-cells (P = 0.005), natural killer (NK; CD16+) cells (P = 0.0001), CD25+ cells (P = 0.004), and HLA-DR+ cells (P = 0.001) accumulating in the tumor stroma. In the tumor parenchyma, NK cells (P = 0.0001) and HLA-DR+ cells (P = 0.003) were increased after IL2 therapy. The T:NK cell ratios in the tumor stroma and parenchyma were decreased after therapy, suggesting selective accumulation of NK cells. By flow cytometry, TIL recovered from post-IL2 biopsy tissues were enriched (P < 0.05) in CD3-CD56+ (NK) cells. In situ hybridization with [35S] cDNA probes for cytokines and IL2 receptors indicated that the numbers of cells expressing mRNA for IL2, tumor necrosis factor alpha, IL1-beta, gamma-interferon, transforming growth factor beta, and IL2 receptor p55 or p70 were increased in post-IL2 biopsy tissues as compared to pre-IL2 tissues. Cytolytic activity of TIL isolated from post-IL2 tissues was also increased, as determined in 4-h 51Cr release assays against K562 targets (12 +/- 3 mean lytic units/10(7) cells +/- SEM pre-IL2 versus 46 +/- 13 post-IL2; n = 16) and against autologous tumor (13 +/- 8 versus 68 +/- 26; n = 9). Fresh TIL of one clinical responder showed relatively high levels (195 lytic units) of autotumor cytotoxicity after IL2 therapy versus no activity prior to therapy. In the blood, NK and lymphokine-activated killer cell activity, and percentages of CD3-CD56+ NK cells and of activated (CD25+) T-lymphocytes were increased for all doses of IL2.(ABSTRACT TRUNCATED AT 400 WORDS)

Cytogenetic analysis of a cemento-ossifying fibroma from a patient with nonfamilial bilateral multicentric retinoblastoma revealed three reciprocal translocations with the karyotype 46,XY,t(1;18)(q21;q21.3),t(3;10)(p13;q22),t(6;11)(p22;p15). Routine and high-resolution cytogenetic analysis of peripheral blood leukocytes showed an apparently normal, 46,XY chromosome pattern with no deletion of chromosome 13. Molecular analysis demonstrated no gross differences in the retinoblastoma gene or the TP53 gene between constitutional and tumor DNA. This is the first cytogenetic analysis of a cemento-ossifying fibroma and the first report of this tumor in a retinoblastoma patient. The data may be added to the small, but growing literature on cytogenetic aberrations in benign tumors and may lend insight into genes involved in cell proliferation and neoplastic transformation.

We compared the phenotype and antitumor effector function of lymphocytes obtained from tumor tissues, lymph nodes, and the peripheral blood of patients with head and neck cancer. Freshly isolated tumor-infiltrating lymphocytes were deficient in CD4+ T cells in comparison with lymph node lymphocytes (LNL) and peripheral blood lymphocytes. A significantly higher CD4/CD8 ratio observed in LNL vs tumor-infiltrating lymphocytes and peripheral blood lymphocytes was attributable to both a significant enrichment in CD4+ T cells as well as a decrease in CD8+ T cells. The percentage of natural killer cells (CD3-CD56+) was uniformly low in both tumor-infiltrating lymphocytes and LNL. In patients with cervical metastases, LNL contained an increased proportion of CD16+ cells. Tumor-involved lymph nodes were not enriched in the CD8+C11b+ subset of T "suppressor" lymphocytes compared with uninvolved lymph nodes. Also, tumor-involved lymph nodes had significantly fewer CD4+ T cells than did uninvolved lymph nodes. In comparison with peripheral blood lymphocytes, freshly isolated tumor-infiltrating lymphocytes and LNL were depleted of cytotoxic effector cells, as indicated by low or absent cytotoxic activity against tumor cell targets. The ability to generate lymphokine-activated killer cells was significantly reduced in LNL in comparison with peripheral blood lymphocytes. In patients with head and neck cancer, depressed local and regional antitumor responses are associated with a deficiency of functional cytotoxic effector cells rather than an increase in suppressor T lymphocytes.

The clinical, light, and ultrastructure features of a myoepithelioma occurring on the hard palate of a 24-year-old woman are presented and compared with 41 myoepithelioma of the head and neck described in the English literature. These 42 tumors (39 benign and 3 malignant) occurred in individuals from 14 to 81 years of age, affected both sexes about equally, and most often presented as a slowly enlarging, asymptomatic mass. The parotid gland and palate were the most common sites of occurrence. The tumors are typically circumscribed and encapsulated, vary from 1 to 5 cm in the greatest dimension, and are composed of spindled and/or plasmacytoid myoepithelial cells. Prognosis correlates with histologic appearance and parallels that of the pleomorphic adenoma. Conservative excision with a margin of uninvolved tissue is curative. The differential diagnosis and histogenic relationship with other closely related neoplasms are discussed.

Patients with advanced, incurable squamous cancer of the head and neck were randomly assigned to treatment with weekly methotrexate alone or methotrexate with Corynebacterium parvum given subcutaneously in weekly bilateral doses in sites around the neck. The addition of C. parvum did not alter the response rate, response duration, survival (either median or long-term) or severity of toxic effects compared to treatment with methotrexate alone. Response rates were higher for patients without distant metastases, ambulatory patients, and those younger than age 65 years. Median survival was improved for responders to chemotherapy and for those initially ambulatory. C. parvum given subcutaneously has no place in the treatment of far advanced cancer of the head and neck.

The clinical and pathologic features of 12 cases of malignant fibrous histiocytoma of the head and neck were studied. These tumors occurred in seven men and five women ranging in age from 21 to 75 years (average, 55 years). The sinonasal tract was the most common site (four cases), followed by the parotid area (two cases), oral cavity (two cases), soft tissues of the neck (two cases), mandible (one case), and larynx (one case). Pathologically, 11 of the tumors were subclassified as storiform-pleomorphic and one as inflammatory. All were treated initially with surgery with or without postoperative irradiation. Five (42%) of the patients experienced local recurrences, three (25%) developed distant metastases (especially to the lungs), and five (42%) died of their disease, all of the latter occurring within two years of diagnosis. No patient developed bona fide cervical lymph node metastasis, although one did have a positive paraparotid node as a result of direct extension from an adjacent tumor.

To elucidate the natural history of dermatofibrosarcoma protuberans of the head and neck, 17 cases were reviewed and compared with 92 others contained within the English literature. The prototypic case is seen as a firm, solitary, slowly enlarging, asymptomatic, cutaneous nodule between 2 and 5 cm in size and of two years' duration. It is more common in men and in persons aged between 30 and 40 years. The scalp and neck-supraclavicular fossa are the most common sites, accounting for half of the cases. Approximately 50% to 75% of the patients experience local recurrence after initial surgery and, of these, half to three fourths manifest within three years of treatment. Metastases, seen in no more than 6% of all cases, are almost invariably preceded by two or more local recurrences and occur primarily through the bloodstream to the lungs and bones and less often to regional lymph nodes. Prognostic factors, differential diagnosis, and histogenesis are included.