Jacqueline A. Wieneke

Sinonasal tract and nasopharyngeal melanomas: a clinicopathologic study of 115 cases with a proposed staging system.

&NA; Primary sinonasal tract mucosal malignant melanomas are uncommon tumors that are frequently misclassified, resulting in inappropriate clinical management. A total of 115 cases of sinonasal tract mucosal malignant melanoma included 59 females and 56 males, 13–93 years of age (mean 64.3 years). Patients presented most frequently with epistaxis (n = 52), mass (n = 42), and/or nasal obstruction (n = 34) present for a mean of 8.2 months. The majority of tumors involved the nasal cavity (n = 34), septum alone, or a combination of the nasal cavity and sinuses (n = 39) with a mean size of 2.4 cm. Histologically, the tumors were composed of a variety of cell types (epithelioid, spindled, undifferentiated), frequently arranged in a peritheliomatous distribution (n = 39). Immunohistochemical studies confirmed the diagnosis of sinonasal tract mucosal malignant melanomas with positive reactions for S‐100 protein, tyrosinase, HMB‐45, melan A, and microphthalmia transcription factor. Sinonasal tract mucosal malignant melanomas need to be considered in the differential diagnosis of most sinonasal malignancies, particularly carcinoma, lymphoma, sarcoma, and olfactory neuroblastoma. Surgery accompanied by radiation and/or chemotherapy was generally used. The majority of patients developed a recurrence (n = 79), with 75 patients dying with disseminated disease (mean 2.3 years), whereas 40 patients are either alive or had died of unrelated causes (mean 13.9 years). A TNM‐type classification separated by anatomic site of involvement and metastatic disease is proposed to predict biologic behavior.

Spindle cell (sarcomatoid) carcinomas of the larynx: A clinicopathologic study of 187 cases

Laryngeal spindle cell (sarcomatoid) carcinomas are uncommon tumors, frequently misdiagnosed as reactive lesions or mesenchymal malignancies. The records of 187 patients with tumors diagnosed as laryngeal spindle cell (sarcomatoid) carcinoma were retrieved from the files of the Otorhinolaryngic Tumor Registry of the Armed Forces Institute of Pathology. There were 174 men and 13 women, 35–92 years of age (average, 65.6 years). Nearly all patients experienced hoarseness (n = 165 [88%] patients) for a mean duration of 11.0 months. Patients admitted to smoking (n = 162 [87%] patients) and/or alcohol use (n = 90 [48%] patients). Most tumors were glottic (n = 132 [71%]), T1 (n = 111 [59%]), 1 and polypoid (n = 185 [99%]), with a mean tumor size of 1.8 cm. Histologically, squamous cell carcinoma (n = 157 [84%]) was noted, ulcerated, and blended with the spindle cell component, which was most frequently arranged in a storiform pattern (n = 92 [49%] tumors). Foci of benign or malignant cartilage and/or bone (n = 13 [7%]) were noted in the spindle cell component. All patients were treated with surgery (n = 90 [48%] patients) or surgery with radiation (n = 97 [52%] patients). Recurrences developed in 85 (45%) patients. Overall, T1 glottic tumors managed by complete surgical eradication had the best outcome (mean follow-up, 7.8 years).

Adrenal cortical neoplasms in the pediatric population: a clinicopathologic and immunophenotypic analysis of 83 patients.

Adrenal cortical neoplasms in pediatric patients (<20 years) are rare. The clinical manifestations and biologic behavior of these lesions can be quite distinct from their histologically similar counterparts in the adult population, making pathologic criteria for distinguishing benign from malignant tumors equivocal. We undertook a study of 83 adrenal cortical neoplasms to determine if adult clinical and histologic features can be applied to pediatric patients in an outcome-based analysis. Most of the patients (50 girls and 33 boys) presented with hormone-related symptoms present for a mean of 6.8 months. The tumors ranged in size from 2 to 20 cm (mean 8.8 cm). Histologic parameters examined included capsular and/or vascular invasion, extraadrenal soft tissue extension, growth pattern, cellularity, necrosis, cytoplasmic eosinophilia, nuclear pleomorphism, nuclear-to-cytoplasmic ratio, prominent nucleoli, mitotic figures, atypical mitotic figures, bands of fibrosis, and calcifications. Immunophenotypically, there was reactivity with inhibin, vimentin, CK5, and focally with p53 and Ki-67. All patients underwent adrenalectomy, and 20 patients received adjuvant therapy. All patients with tumors classified as adenomas (n = 9) were alive, without evidence of disease (mean 14.7 years), whereas 21 patients with carcinomas had died with disease (mean 2.4 years). Only 31% of histologically malignant tumors behaved in a clinically malignant fashion. Features associated with an increased probability of a malignant clinical behavior included tumor weight (>400 g), tumor size (>10.5 cm), vena cava invasion, capsular and/or vascular invasion, extension into periadrenal soft tissue, confluent necrosis, severe nuclear atypia, >15 mitotic figures/20 high power fields, and the presence of atypical mitotic figures. Vena cava invasion, necrosis, and increased mitotic activity (>15 mitotic figures/20 high power fields) independently suggest malignant clinical behavior in multivariate analysis.

Diffuse sclerosing variant of papillary thyroid carcinoma: a clinicopathologic and immunophenotypic analysis of 22 cases.

Background: The diffuse sclerosing variant of papillary thyroid carcinoma (DSV-PTC) is an uncommon tumor making up about 2% of all papillary thyroid carcinomas. Previous studies have not comprehensively evaluated these tumors in a large series of patients.Design: Twenty-two cases of DSV-PTC diagnosed between 1970 and 2000 were identified in the files of the AFIP. Histologic and immunohistochemical features were evaluated and patient follow-up was obtained.Results: The tumors affected 14 females and 8 males, aged 6 to 49 yr (mean, 18 yr), with males presenting at a mean older age than females (24 vs 14 yr). Symptoms included an enlarging mass in the thyroid, present for a mean of 9.5 mo. While a dominant tumor was identified in a single lobe, bilateral disease was common (n=16). The dominant mass ranged in size from 1.7 to 5.8 cm in diameter (mean, 3.8 cm). Histologically, all cases demonstrated a papillary carcinoma (conventional, solid, or follicular pattern) diffusely involving the gland. Extrathyroidal extension, lymphocytic thyroiditis, squamous metaplasia, increased fibrosis/sclerosis, and psammoma bodies were present to a variable degree. Both the papillary carcinoma and squamous metaplasia cells were strongly immunoreactive with CK19, thyroglobulin, and TTF-1. An increased number of S-100 protein immunoreactive dendritic cells were recognized. p53 was increased (>15%) in the tumor cells in 12 patients, while Ki-67 was increased in the tumor cells in two patients. Perithyroidal and cervical lymph node metastasis occurred in 18 (82%) patients. All metastases demonstrated histologic features similar to the primary. Complete resection (thyroidectomy in 18 patients) with lymph node dissection, yielded a 95% 5-yr survival without evidence of disease. One patient died of disease after a malignant transformation of the squamous metaplasia into squamous cell carcinoma.Conclusions: The recognition of DSV-PTC can be made with the following features: classic to solid foci of PTC, lymphocytic thyroiditis, squamous metaplasia, increased fibrosis, and innumerable psammoma bodies. DSV-PTC is more biologically aggressive than conventional PTC, but the patients’ survival is not significantly different. This diagnosis should lead the clinician to aggressively manage these patients (thyroidectomy and lymph node dissection) in an effort to achieve an excellent long-term clinical outcome.

Paraganglioma: Carotid Body Tumor

Extra-adrenal paragangliomas are neoplasms of the paraganglia located within the paravertebral sympathetic and parasympathetic chains. Thus paragangliomas may arise anywhere along these tracts and common sites of occurrence include abdomen, retroperitoneum, chest and mediastinum and various head and neck locations such as jugulotympanic membrane, orbit, nasopharynx, larynx, vagal body and carotid body. Recent literature suggests a molecular basis for the development of some paragangliomas, i.e. germline mutations. Six genes have been identified and are thought to contribute to the development of pheochromocytoma/paraganglioma. These include RET, VHL, NF1 and SDH subunits SDHB, SDHC, and SDHD. SDHD and SDHB mutations account for a significant percentage of head and neck paragangliomas. It is well know that paragangliomas may be hereditary and may be part of genetic syndromes such as Von Hippel-Lindau syndrome, neurofibromatosis type I (von Recklinghausen disease), MEN 2A and MEN 2B. When features of these more commonly known syndromes are not present, many familial cases, often associated with the above mentioned germline mutations, go unrecognized. In the head and neck region the normal paraganglia are associated with the parasympathetic nervous system and paragangliomas arising from these parasympathetic sites account for up to 70% of extra-adrenal paragangliomas. The most common site is the carotid body. Carotid body paragangliomas arise at the bifurcation of the internal and external carotid arteries and have classic radiographic

Giant Cell Tumor of the Larynx: A Clinicopathologic Series of Eight Cases and a Review of the Literature

True giant cell tumors of the larynx (GCTL) are quite rare, and only individual case reports are documented in the literature. Eight cases of GCTL were identified in the Otorhinolaryngic Pathology Tumor Registry between 1966 and 2000. There were 2 women and 6 men, ages 26 to 62 years (mean, 44.5 yrs). Patients presented with a palpable neck mass (n = 5), airway obstruction (n = 3), hoarseness (n = 3), and dysphagia (n = 2). All tumors involved the thyroid cartilage, a few with local extension. The mean tumor size was 4.1 cm. Histologically, the tumors showed no connection to the surface epithelium and arose in sites of ossification. The tumors had an expansile, infiltrative growth and consisted of numerous multinucleated osteoclast-like giant cells within a cellular stroma composed of plump, oval mononuclear cells. Of interest was that the nuclei of the giant cells were similar to the nuclei of the stromal cells. Treatment included biopsy only with adjuvant therapy (n = 2), local resection (n = 3), and total laryngectomy (n = 3). Follow-up showed 5 patients were alive without evidence of disease (mean follow-up, 6.9 yrs); 2 died of unrelated causes (mean survival, 22.2 yrs). No patients developed recurrences. GCTL are rare tumors that can cause significant airway obstruction. Complete surgical resection yields an excellent outcome without adjuvant therapy.

Laryngeal angiosarcoma: a clinicopathologic study of five cases with a review of the literature.

Objective Primary laryngeal angiosarcoma (LA) is rare without a reported series evaluating these tumors.