Neuroendocrine Tumors of the Head and Neck: A Selected Review with Emphasis on Terminology

Virtually every variant of neuroendocrine neoplasia can occur, at least rarely, in the head and neck region. This review focuses on the terminology surrounding neuroendocrine carcinomas of the larynx and their distinction from morphologically similar but biologically distinctive neoplasmas. It is suggested that rare typical laryngeal carcinoids be labeled as such. There is little evidence that these lesions are part of a morphologic continuum. In contrast, more common “carcinoid-like” carcinomas, previously referred to as “atypical carcinoids” are more appropriately labeled as “moderately differentiated neuroendocrine carcinomas”. These neoplasms should, in turn, be distinguished from “small cell neuroendocrine carcinomas,” although these latter two neoplasms do represent a morphologic and behavioral spectrum. Light microscopic and immunohistochemical features distinguishing neuroendocrine carcinomas of the larynx from paraganglioma, metastatic medullary carcinoma, malignant melanoma, and basaloid squamous cell carcinoma are presented. The second portion of this review outlines the clinicopathologic features of two head and neck neoplasms exhibiting varying degrees of neuroendocrine differentiation. Olfactory neuroblastomas have well-developed neuroendocrine differentiation, almost invariably arise from the olfactory mucosa, typically exhibit low-grade cytologic features, and may have protracted clinical course with an approximately 50% overall 5-yr survival. In contrast, sinonasal undifferentiated carcinoma is a microscopically high-grade neoplasm with minimal, abortive neuroendocrine features, a highly aggressive clinical course, and virtually 100% mortality. They can arise throughout the sinonasal region. Presented at the Endocrine Pathology Society—USCAP Meeting, Washington, DC, March 23, 1996.     

Primary intramedullary spinal cord primitive neuroectodermal tumor with intracranial seeding in an infant

Primary spinal cord primitive neuroectodermal tumor (PNET) is a rare entity. In all, 13 cases have been reported in the literature, including 3 with intracranial seeding. A 3-month-old girl with involvement of the spinal cord below the mid-thoracic level is described. The brain MRI revealed findings indicative of seeding along the intracranial subarachnoid space. Biopsy, duraplasty and removal of laminotomy flap were done. In spite of a good response to the first cycle of postoperative 8-drugs-in-a-day chemotherapy, further treatment was refused. She died 21 days after the onset of leg weakness, which reveals the rapid progression of untreated cases. To our knowledge, this is the first case of spinal cord PNET with parenchymal involvement that has been described in an infant.     

Interferon-β inhibits proliferation and progression through S phase of the cell cycle in five glioma cell lines

Summary The growth inhibitory effect of IFN- was evaluated in 5 human glioma cell lines (AO2V4, GJC, GJR, NN and NNR) and in normal astrocyte cultures (SC and TM). All 5 glioma cell lines showed an anti-proliferative response to IFN- whereas normal glial cells were non-responsive. IFN- at 10, 100 and 500 U/ml lead to a 30%,70% and 80% relative decrease in cell number after 12 days, respectively in AO2V4 cells. GJC and GJR cell lines also responded significantly to the lowest concentration of IFN- tested and at 500 U/ml the relative cell number decreased 55%. The NN and NNR cells were the least responsive to IFN- with maximum growth inhibition of 30% at 500 U IFN-/ml. Following treatment with IFN-, AO2V4, GJC, GJR and normal astrocytes all expressed mRNA encoding the anti-viral protein, 2-5A synthetase demonstrating that IFN- bound to receptors on all four cell lines and activated signal transduction pathways required for induction of an anti-viral protein. A determination of the relative number of viable cells showed that none of these cells exhibited a significant decrease in cell viability. Since the antiproliferative response to IFN- was not primarily due to cell death, the effect of IFN- on cell cycle progression was evaluated by flow cytometry. All treated glioma cell lines showed a relative increase in proportion of cells in S phase. AO2V4 cells had a 50%–80% increase in the percentage of cells in S phase, whereas GJC, GJR and NNR had percentage increases of 20%–40%. IFN- treatment of normal astrocytes did not significantly alter their cell cycle profile. These data suggest that IFN- exerts its antiproliferative effect on glioma cells by arresting the ordered progression through S phase or decreasing entry into G₂/M phase of the cell cycle.     

Breast cancer vascularity: Color Doppler sonography and histopathology study

Summary In this prospective study, the authors examined 50 patients with breast tumors (malignant, n = 32; benign, n = 18) to investigate the correlation between color Doppler flow mapping and histopathological findings and to evaluate the clinical significance of color Doppler mapping. Among the 32 patients with breast cancer, color Doppler signals were detected in 24 patients (75%). The maximum flow velocities varied from 5 to 34 cm/sec, with 16 (67%) of them above 15 cm/sec. Among the 18 patients with benign tumors, color Doppler signals could be detected in 7 (39%). The maximum flow velocity varied from 3 to 30 cm/sec but was over 15 cm/sec in only two patients (28%). Histological studies revealed that color Doppler signals detected by Doppler sonography correlated with disordered neovascularization penetrating the lesion from its periphery, consisting of thin-walled blood vessels and large arteriovenous shunts. Although large tumors tend to have high Doppler flow, there is no significant correlation between the maximum flow velocity and tumor size. There is also no significant correlation between the detection of high flow color Doppler signals and the age, receptor status, tumor size, lymph node metastases, or clinical stage of patients with breast cancer. However, there is a positive association (p < 0.05) between nodal metastases and higher tumor flow velocity in T1 ( 2 cm) breast tumors, but not in larger tumors. It is concluded that color Doppler is useful in the assessment of tumor vascularity but is of limited value in the differentiation of benign from malignant lesions. However, the presence of color Doppler signals in Tl breast cancer suggesting early dissemination of the cancer might be of important clinical significance in detecting those small, apparently early, but aggressive tumors with poor prognosis.     

Volumetric reconstruction and stereotactic computer assisted resection in intracerebral lesions

Summary Since 1990 112 patients have undergone Stereotactic resection of intra-axial tumoural lesions with volumetric reconstruction, using the Kelly-Goerss system. Stereotactic integration of CT, angiographic and particularly MRI information, together with three-dimensional information of the lesion, provide an innovative evaluation of the most appropriate surgical approach, even for each single patient. The main limitation of this surgical method is in cases where the infiltrating part of the tumour is pre-eminent, while it can allow macroscopically complete resection of well circumscribed lesions, almost independently of their location and volume. Some technical aspects of Stereotactic resection of brain tumours are discussed in the light of our experience.     

The possible role of TNF-α and IL-2 in inducing tumor-associated metabolic alterations

This study was conducted to investigate the role of tumor necrosis factor- (TNF-) and interleukin-2 (IL-2) in inducing cancer cachexia, and the results were compared with those obtained from our previous study on Fisher 344 rats with methylcholanthrene-induced sarcoma. Three groups of male Fisher 344 rats received one of the following regimens: 4×10⁴ IU of human recombinant TNF- per rat per day subcutaneously (sc) for 5 consecutive days (n=5), 3.5×10⁵ U human recombinant IL-2 per rat per day sc for 14 consecutive days (n=5), or normal saline (n=5). The activities of both phosphoenolpyruvate carboxykinase (PEPCK) and malic enzyme (ME) were increased slightly in the IL-2 group. Furthermore, LPL activity was significantly increased in the adipose tissue of the TNF group and in the cardiac muscle of the IL-2 group, but not in that of the TNF group. These results show that there is a significant difference between the metabolic alterations seen in the tumor-bearing state and those induced by either TNF- or IL-2 alone. Thus, it is unlikely that IL-2 or TNF- is the sole mediator of cancer cachexia in this tumor and rat model.     

Serum tumor marker kinetics and the clinical course of patients with advanced breast cancer

Serum carcinoembryonic antigens (CEA), CA 15-3, and tissue polypeptide antigens (TPA) have been used in monitoring the clinical course of patients with breast cancer. However, recent reports have suggested that the serial levels of these markers during therapy do not always correlate with the response to therapy. To clarify the usefulness of the serial combination assay of these markers in monitoring the clinical course of patients during therapy, we investigated the relationship between the initial changes and the kinetic patterns of the markers after therapy and the objective responses. When an increase or decrease of over 20% in these markers is taken to be significant, then the initial changes in all three markers significantly correlated with the therapeutic responses (P<0.01). Five distinct kinetic patterns in the marker levels were observed. A paradoxical kinetic pattern of CEA and CA 15-3 levels — that is, an initial surge and subsequent drop — was seen in one-third of the responders. The TPA levels tended to exhibit a steady decline pattern in those responders. The sensitivity and specificity of the kinetic patterns to predict the clinical courses were significantly higher than those obtained from the analysis of initial changes. These findings thus suggest that adequate knowledge of the unique kinetics of each marker may help to make a more accurate prediction of the therapeutic responses.     

Use of ultrasound-guided percutaneous needle biopsy in the diagnosis of mediastinal tumors

We herein report the usefulness of ultrasoundguided percutaneous needle biopsy for histological diagnosis in 18 patients with mediastinal tumors. Computed tomography revealed these tumors to be in contact with the chest wall. The preoperative diagnosis was thymoma in 7 patients, germinoma in 5, neurogenic tumor in 3, and other in 3. The most commonly encountered indication for an ultrasound-guided percutaneous needle biopsy was an anterior mediastinal lesion (78%; 14 of 18 patients). In 16 (89%) of the 18 patients, the biopsy diagnosis corresponded to the post-operative diagnosis. No complications were encountered in any of the patients. This new technique of ultrasound-guided percutaneous needle biopsy is both relatively simple and highly accurate and may thus be useful for outpatients. Preoperative ultrasound-guided percutaneous needle biopsy is thus considered to be a safe and reliable method for the histological diagnosis of mediastinal tumors, and a good alternative to traditional biopsy techniques such as mediastinoscopy or thoracotomy.Presented at the 11th Biennial Asian Congress on Thoracic and Cardiovascular Surgery, Kuala Lumpur, Malaysia, November, 21–25, 1993.     

Multidisciplinary management of metastatic colorectal cancer

When colorectal cancer metastasizes to distant organs, usually multiple sites are involved and treatment consists primarily of systemic chemotherapy and supportive care. Chemotherapeutic agents effective against metastatic colorectal cancer include 5-fluorouracil, often used in combination with leucovorin or methotrexate, and irinotecan (CPT-11). Median survival with optimal chemotherapy regimens ranges from 10 to 15 months. Less frequently, colorectal cancer metastasizes only to the liver or lung. In a minority of these cases, surgical resection can be performed and results in a median survival of 28-46 months for hepatic resections and 24-25 months for pulmonary resections. Five-year survival rates range from 24 to 38% and 21 to 44% for hepatic and pulmonary resections, respectively. For isolated liver metastases that are not surgically resectable, other regional therapies that can be considered are hepatic cryosurgery, radiofrequency ablation, and hepatic arterial infusion chemotherapy. Median survival following cryosurgery is between 26 and 30 months, while median survival following radiofrequency ablation has not been established in large series. Hepatic arterial infusion chemotherapy, especially with newer combination drug regimens, may increase survival in patients with isolated liver metastases compared to systemic chemotherapy, but this must be confirmed in randomized, prospective trials. Colorectal cancer metastases to the brain can be treated with radiation therapy or surgical resection, but median survival with treatment is less than one year.     

Phyllodes tumor of the breast with a grossly malignant appearance: A case report

A huge phyllodes tumor of the breast that appeared grossly malignant in a 43-year-old woman is described. The patient suffered from a large breast tumor that suddenly increased in size over 5 months to occupy the entire breast. The tumor was hard, ulcerated and 20 cm in greatest diameter. Diagnostic imaging (US, CT and MRI) demonstrated a circumscribed mass with a large cystic cavity. She underwent total mastectomy under a diagnosis of malignant breast tumor. Grossly, the cut surface of the tumor showed a large cystic cavity surrounding a fleshy, hemorrhagic and necrotic mass with a lobulared or trabeculared appearance. Unexpectedly, benign phyllodes tumor (PT) without any stromal overgrowth was diagnosed histologically. She has been doing well since total mastectomy. In our case and in many other reported cases, PT does not show any distinctive correlation between pathologic findings and tumor behavior. Thus wide local excision is the preferred initial treatment for PT.