Spindle-cell carcinoma of the aerodigestive tract. An immunohistochemical analysis of 21 cases

Immunohistochemical analysis of 21 prototypic mucosal spindle-cell carcinomas of the aerodigestive tract was performed at the Armed Forces Institute of Pathology (AFIP) to establish the usefulness of selected immunohistochemical markers in distinguishing spindle-cell carcinoma from other mucosal spindle-cell neoplasms. Immunoreactive keratin could be demonstrated in only 13/21 (62%) of cases. Coexpression of keratin and vimentin was demonstrated in 10/17 (59%) of the tumors evaluated for both of these intermediate filaments. All spindle-cell carcinomas lacked S100 protein, which is an immunoreactivity we would expect to find in spindle-cell malignant melanoma, one of the principal considerations in a differential diagnosis. Both alpha-1-antitrypsin (AAT) and alpha-1-antichymotrypsin (ACT) were demonstrated in the tumor cells in all cases. However, albumin had a similar distribution in the tumors, which suggested that passive uptake was a serious confusing factor. The results of this study indicate that AAT and ACT are unreliable markers for distinguishing spindle-cell carcinomas from malignant fibrous histiocytomas.     

Multicentric squamous-cell carcinoma of the upper aerodigestive tract

In an attempt to define the true frequency of multiple primary squamouscell carcinomas of the upper aerodigestive tract, 3 separate population groups were studied. The results of this investigation confirmed the high incidence of multicentric carcinomas in the upper aerodigestive tract, lung, and esophagus. The clinical significance of this phenomenon is discussed, particularly its effect on patient survival and its possible relationship to local tumor recurrence. The value of routine panendoscopy in the initial assessment is stressed as well as the need for a lifelong follow-up of these patients.     

Pseudoaneuploid subpopulations detected in normal upper aerodigestive tract mucosa consistent with physiological apoptosis in normally differentiating squamous mucosa.

OBJECTIVES: While evaluating the validity of using normal human mucosal cells from the upper aerodigestive tract as diploid standards for DNA content studies of squamous cell cancer of head and neck by flow cytometry, pseudoaneuploidy was frequently detected. The purpose of this study was to further evaluate these DNA content abnormalities encountered in normal human mucosal cells and correlate them to physiological apoptosis. STUDY DESIGN: Thirty-two specimens of upper areodigestive tract mucosa from 18 surgical resections, 11 fresh autopsies, and 3 buccal scrapings were examined for DNA content by flow cytometry. RESULTS: Pseudoaneuploidy, which ranged from sub-G0/G1 peaks to hyperdiploid peaks with increased 90 degrees light scattering properties was found in 60% of these specimens. Fluorescent microscopic examination of the sorted DNA pseudoaneuploid cells demonstrated cells undergoing apoptosis. CONCLUSION: This unexpected pseudoaneuploidy in normal mucosal cells was a result of physiological apoptosis, a normal component of squamous differentiation. EBM rating: B-2.     

MUC4 (sialomucin complex) expression in salivary gland tumors and squamous cell carcinoma of the upper aerodigestive tract.

OBJECTIVES: This study investigates MUC4 expression in normal squamous epithelia and squamous cell carcinoma (SCC) of the upper aerodigestive tract (UADT), and in salivary gland neoplasms. Study design: MUC4 antigens in tumor and adjacent normal tissue are localized by immunocytochemical studies. Fresh frozen tissues from surgical resection specimens are further analyzed by Western blot. RESULTS: MUC4 is identified by immunocytochemical staining throughout the normal UADT mucosa, in 34 of 40 primary UADT SCC, and in 11 of 12 metastatic cervical lymph nodes. A trend toward decreased MUC4 staining in moderately and poorly differentiated tumors is noted. Immunoblots show MUC4 in 4 of 5 SCC analyzed. Immunocytochemical staining of MUC4 in 13 major and minor salivary gland neoplasms reveal variable staining of normal and neoplastic tissue. MUC4 is demonstrated in immunoblots of normal parotid tissue and in the single parotid malignancy analyzed, but is not demonstrated in one minor salivary gland malignancy. These findings characterize normal UADT mucosal and salivary MUC4 expression, and MUC4 expression in SCC of the UADT and in salivary gland tumors. SIGNIFICANCE: Correlation of MUC4 expression with clinical outcomes may establish MUC4 as a potential molecular prognostic marker for these tumors.     

Transoral robotic surgery: role in the management of upper aerodigestive tract tumors

The toxicity associated with concomitant chemoradiation for the management of laryngeal and pharyngeal carcinoma has been well documented. Minimally invasive surgical techniques offer the potential to extirpate the malignancy as a single-modality therapy and provide essential information that may direct subsequent treatment. In selected patients, radiation doses may be reduced and systemic chemotherapy may be withheld after tumor extirpation. Transoral laser microsurgery has proven effective, although inability to manipulate and suture tissue by this modality limits ablation and reconstruction of extensive defects. Transoral robotic surgery is a relatively new technique that provides several unique advantages, which include a 3-dimensional magnified view, ability to see and work around curves or angles, and the availability of 2 or 3 robotic arms that can be used to reconstruct extensive defects using either local, regional, or free flaps. Preliminary data suggest that transoral robotic surgery may provide a technique for ablation and reconstruction of pharyngeal defects that may be superior to other transoral techniques. It may also provide a means for personalizing therapy for oropharyngeal and supraglottic carcinoma.     

Surgical treatment of invasion of the upper aerodigestive tract by well-differentiated thyroid carcinoma

Forty-eight patients with well-differentiated thyroid carcinoma invading upper aerodigestive tract structures have been described. Age at diagnosis was found to be a negative prognostic factor, and duration of disease before invasion was found to be a positive prognostic factor. Treatment with radical surgery and adjuvant therapy provided no improvement in survival over treatment with near-total (skeletonizing) excisions combined with adjuvant therapy. All patients treated with partial debulking procedures, with or without tracheotomy, died from disease. We believe that partial resection of upper aerodigestive tract structures without sacrifice of voice, normal breathing, or swallowing should be considered in patients with well-differentiated thyroid carcinoma.     

Simultaneous carcinomas of the esophagus and upper aerodigestive tract

A review of 150 consecutive head and neck cancer patients over a 22-month period revealed a multiple primary cancer rate of 19%, 9% in the head and neck region. Nine patients (6%) had simultaneous esophageal and head and neck cancers. Complete systematic esophagoscopic examinations, in addition to barium swallow radiographic studies, are recommended for all patients with head and neck cancers.     

Association between malignancies of the upper aerodigestive tract and uterine cervix.

Cancers of the cervix and buccal cavity share histologic, epidemiologic, and exposure characteristics. In particular, cigarette smoking and human papillomavirus (HPV) have been cited as etiologic cofactors of both malignancies. Using incidence data from the Surveillance, Epidemiology, and End Results (SEER) program of the National Cancer Institute for the years 1973 through 1984, we evaluated the incidence of second cancers of the buccal cavity following an initial cervical cancer. Standardized incidence ratios (SIR) were uniformly elevated for both white (SIR = 2.0), and black (SIR = 3.5) women. There were also elevated risks for the development of cervical cancer following an initial buccal cavity cancer (SIRs = 3.3 and 2.5, respectively). A similar pattern was evident for laryngeal cancer among white women. HPV transmission could account in part for the paired occurrence of these two anatomically distinct cancer sites. Cigarette smoking could act as a synergistic cofactor in the malignant transformation of viral genome-harboring tissue.     

Clinicopathological study of upper urinary tract tumors associated with bladder tumors

Among 535 cases of urothelial tumors (upper urinary tract and bladder tumors) from 1970 to 1988, 40 had upper urinary tract tumor associated with bladder tumor. Of 40 cases, 18 (45%) were synchronous, 17 (43%) were metachronous with primary upper urinary tract tumor followed by subsequent bladder tumor 18.5 +/- 14.1 (means +/- SD) months later and 5 (12%) were metachronous with primary bladder tumor followed by subsequent upper urinary tract tumor 40.2 +/- 13.6 months later. The incidence (17/52 = 0.32) of bladder tumor occurrence subsequent to primary upper urinary tract tumor was much higher than that (5/465 = 0.01) of upper urinary tract tumor subsequent to primary bladder tumor. The histologic grades of upper urinary tract tumor and associated bladder tumor were consistent in 73%. Except in 1 case, multiple occurrence of upper urinary tract tumor was always observed unilaterally on the side involved. The current results not only support the theory of multicentricity but raise the possibility that tumor cell implantation may play some role at least in the development of bladder tumor subsequent to upper urinary tract tumor.     

Epithelial-myoepithelial carcinoma: a review of the clinicopathologic spectrum and immunophenotypic characteristics in 61 tumors of the salivary glands and upper aerodigestive tract

To further define the clinicopathologic spectrum of epithelial-myoepithelial carcinoma (EMCa), we report the gross, histologic, and immunophenotypic characteristics of 61 tumors seen within a 30-year-period. The mean age at presentation was 60.9 years, with a female predominance (1.5:1). The most common sites were parotid (62.1%), sinonasal mucoserous glands (10.3%), palate (8.6%), and submandibular (8.6%). Most EMCas showed a characteristic nodular/multinodular growth pattern and classic biphasic tubular histology. However, new morphologies in EMCa such as ancient change (8.2%), "Verocay"-like change (3.3%), and sebaceous differentiation (13.1%) were noted. Specific histologic variants were dedifferentiated EMCa (3.3%), oncocytic EMCa (8.2%), EMCa ex pleomorphic adenoma (1.6%), double-clear EMCa (3.3%), and EMCa with myoepithelial anaplasia (3.3%). All cytokeratin cocktails selectively highlighted the epithelial component well. Of the myoepithelial markers, p63, smooth muscle actin and vimentin performed best. Bcl-2 and c-kit were frequently positive (66.7% and 69.2%, respectively). p53 was highly expressed only in 1 dedifferentiated EMCa. The recurrence rate was 36.3% (median disease-free survival 11.34 y), but death was rare with 5-year and 10-year disease-specific survivals of 93.5% and 81.8%, respectively. The most important univariate predictors of recurrence were margin status (log rank P=0.006), angiolymphatic invasion (P=0.002), tumor necrosis (P=0.004), and myoepithelial anaplasia (P=0.038). Thus, EMCa is generally a low-grade tumor with a broader morphologic spectrum than previously thought, with several key features predictive of recurrence. Immunohistochemistry can aid diagnosis by highlighting the biphasic nature of the tumor.     

Selective neck dissections for squamous carcinoma of the upper aerodigestive tract: patterns of regional failure.

BACKGROUND: Surgeons have been using selective neck dissections in the treatment of squamous carcinoma of the upper aerodigestive tract for over 20 years. To date, no data is available that can answer the question "What are the patterns of failure in the neck following a selective neck dissection and is a selective neck dissection a reliable procedure for metastatic disease?" METHODS: To answer this question, the medical records of all patients with squamous carcinoma of the oral cavity, oropharynx, larynx, and hypopharynx treated at The University of Texas M. D. Anderson Cancer Center from January 1, 1985-December 31, 1990, with a selective neck dissection were reviewed. Five hundred seventeen neck dissections were analyzed: suprahyoid (41), supraomohyoid (284), and anterolateral (192). The end point of the study was regional failure and survival. RESULTS: Regional recurrence in patients treated with a suprahyoid dissection was 43% with pathologically positive nodes. The regional recurrence in the patients treated with a supraomohyoid neck dissection was 1.9% with pathologically negative nodes, 35.7% with path N1 without postoperative radiation therapy, and 5.6% with postoperative radiation therapy. The neck staged pathologically N2B failed with and without postoperative radiation, 8.3% and 14%, respectively. Thirteen percent of the anterior/lateral neck dissections failed regionally. If multiple pathologically positive nodes (N2B) were present, the regional failure with postoperative radiation was 30% and 33.3% without postoperative radiation. CONCLUSION: The results of this retrospective study suggest that a selective neck dissection is a satisfactory staging procedure and is a definitive operation if all the nodes are pathologically negative. However, if a node is found to be invaded with cancer, the use of postoperative radiation is advisable.     

Endoscopy and intubation in cancer of the upper aerodigestive tract

The pathogenesis of upper airway obstruction from cancer arising in the larynx, pyriform fossa and oropharynx is discussed. Endotracheal intubation for general anaesthesia can be a hazardous procedure and alternatives are presented.     

Role of routine panendoscopy in cancer of the upper aerodigestive tract.

Patients with squamous cell carcinoma of the aerodigestive tract routinely undergo panendoscopy to detect possible synchronous second primary tumors. The aim of our study was to assess the incidence of synchronous and metachronous second primary tumors and to refine the role of panendoscopy. The charts of 358 patients evaluated by means of panendoscopy during work-up of a first primary squamous cell carcinoma of the upper aerodigestive tract were reviewed. The incidence of a second primary tumor was 16.2%, with 6.4% being synchronous and 9.8% being metachronous. In only 3.1% of all patients, a synchronous tumor was clinically silent and only revealed by means of the panendoscopy. The synchronous tumors were mainly in the oral cavity, pharynx, or larynx (61%), whereas the metachronous tumors were most likely in the lung (57%). Despite the low incidence of synchronous second primary tumors, we still recommend panendoscopy for assessment of the primary tumor and as a training field for residents.     

Bronchiolo-alveolar carcinoma with nodal metastases. An ultrastructural study.

A case of bronchiolo-alveolar carcinoma of the lung was studied by light and electron microscopy. Type II granular pneumocytes were seen in the lymph node metastases of the tumor, a finding not reported previously. We feel that the presence of these cells in metastatic foci indicates their neoplastic nature, and provides evidence that bronchiolo-alveolar carcinoma arises from type II cells.     

Premalignant changes in normal appearing epithelium in patients with squamous cell carcinoma of the upper aerodigestive tract

Biopsy specimens of “normal” mucous membrane of patients susceptible to the effects of the carcinogens of tobacco revealed morphologic abnormalities on electron microscopic examination that were consistent with the concept that carcinogenesis is a multistep process of sequential neoplastic development extending over a long period of time. Such changes in the upper aerodigestive tract are probably tobacco induced and may be reversible if tobacco exposure is eliminated. Use of the electron microscope can provide the clinician with an accurate assay of the severity of mucosal alterations induced by tobacco. The ability to detect such morphologic abnormalities should provide another deterrant to smoking and a useful tool in the further study of these phenomena.     

The pathology of head and neck tumors: papillomas of the upper aerodigestive tracts, Part 18

The human papillomavirus class of DNA viruses are more than circumstantially related to oral and airway papillomas. Whether they are fully oncogenic, in the malignant sense, without other agents is questionable. Recent advances in molecular virology and the use of genus-specific (common) antigen-antibody reactions have identified papillomavirus in laryngeal and oral papillomas. Laryngeal and oral papillomas could be precancerous lesions, but they show a low-risk and long-time interval leading to malignancy unless significant iatrogenic or host variables--such as radiotherapy or immuno-incompetence--are added. Two different papillomas in the larynx can be recognized; a nonkeratinizing, papillomavirus-related lesion, and a keratinizing, usually solitary papilloma, which may or may not be related to a virus genesis and may be equated with a keratosis or clinical leukoplakia.     

Peripheral spindle-cell carcinoid tumor of the lung with type II pneumocyte features. An ultrastructural study with comments on possible histogenesis

A peripheral spindle-cell carcinoid tumor of the lung was studied with the electron microscope. Tumor cells contained dense-core, neurosecretory granules, indicative of their carcinoid identity, and lamellar bodies indistinguishable from those of type II pneumocytes. This observation supports the concept that lung tumors with different histologic and growth patterns may have a common histogenetic basis.