Monoclonal antibody (G10) to a common antigen of human squamous cell carcinoma: binding of the antibody to the H type 2 blood group determinant.

The IgM monoclonal antibody G10 was raised against the human squamous cell carcinoma (SCC) cell line UM-SCC-1. In initial screening against cultured cells, G10 bound to 2 SCC lines (UM-SCC-1 and UM-SCC-13) and 1 pancreatic carcinoma line (UM-PAd-1) but not to cultured fibroblasts (WI-38), ovarian carcinoma cells (SK-OV-3), or malignant melanoma cells (SK-MEL-28 and MeWo). In subsequent tests against cultured cell lines, G10 gave positive reactions with 30 of 33 SCC lines but only 4 of 29 non-SCC lines. The non-SCC lines that bound G10 were UM-PAd-1, 2 transitional cell carcinoma lines (T24 and RT4), and 1 melanoma line (SK-MEL-22). When tested against cultures derived from normal skin or mucosa, G10 was reactive with the epitheloid squamous cells but not with the fibroblasts in each culture. The antigen defined by antibody G10 was stable to fixation with Formalin, and its distribution in tissue sections was examined with the use of immunoperoxidase assays. All SCC biopsy specimens examined in this way were reactive with antibody G10. In similar tests against sections of fixed normal tissues, G10 stained the superficial squamous cells of the epidermis and the basal and suprabasal layers of mucosal squamous epithelial cells from the esophagus. All layers of the laryngeal epithelium were positive. Endothelial cells and certain glandular cells were also positive for G10 binding. G10 agglutinated human red blood cells of all blood groups except those from individuals of the Bombay group (Oh) who lack the H blood group determinant. Against defined oligosaccharides, G10 bound strongly only to the monofucosyl H type 2 structure and was slightly cross-reactive with the synthetic difucosyl H type 2 or Y structure. These results are consistent with previous reports of blood group antigen tissue distribution and indicate that the H type 2 determinant is expressed by all or nearly all mucosal squamous cancers. Less frequent expression by cells of other tumor types may correlate with tissue-specific activation of the H gene-specified fucosyltransferase.

Altered antigen expression predicts outcome in squamous cell carcinoma of the head and neck.

Monoclonal antibody UM-A9 identifies an antigen found on the basal surface of epithelial cells and expressed on all of the squamous cell carcinomas (SCC) that we have tested. In a previous study, we showed that cell lines from metastatic or recurrent SCC exhibit stronger expression of the A9 cell membrane antigen than cell lines from the primary tumor of the same donors, suggesting that this marker is associated with tumor progression. Loss of expression in tumor tissue of normal A, B, and H (ABH) blood group antigens has also been linked to clinical behavior in some epithelial cancers. To determine the prognostic significance of these antigen markers, we prospectively evaluated tissue specimens for expression of these markers in a group of 82 consecutive, previously untreated patients with SCC of the head and neck. Three patterns corresponding to strong (pattern 1), intermediate (pattern 2), or weak (pattern 3) A9 antigen expression were observed. Fifty-eight percent of the patients whose tumors had pattern 1 A9 antigen expression and 78% of the patients with loss of blood group antigen had early relapse, compared with only 34% of those with A9 antigen pattern 2 or 3 (P = .042) and 37% of those whose tumors expressed the mature ABH blood group antigen (P = .012). The combination of A9 pattern and ABH blood group antigen expression in tumor tissue was the variable most strongly associated with duration of disease-free survival, even after adjustment for the traditional prognostic factors of tumor site, stage, and TNM classification. Loss of blood group was the most significant single variable associated with early recurrence, but among patients whose tumors retained ABH blood group antigen expression, the A9 pattern distinguished good and poor prognostic groups. To our knowledge, our study is the first to demonstrate that differences in blood group antigen expression are significantly correlated with disease-free survival in SCC of the head and neck. We have initiated a study (a) to determine the relationship of the A9 antigen and the blood group antigens with clinical response of the tumors and (b) to determine whether these markers should be used as prognostic indicators.

Evidence that loss of chromosome 18q is associated with tumor progression.

Four sets of cell lines (UM-SCC-14A, -14B, and -14C; UM-SCC-17A and -17B; UM-SCC-81A and -81B; and UM-SCC-83A and -83B), established from primary and metastatic or locally recurrent tumors from four patients with squamous cell carcinoma of the head and neck, were examined for loss of heterozygosity (LOH) on chromosome 18q. Metastatic or recurrent cell lines from all four exhibited 18q LOH. UM-SCC-14A, -14B, and -14C, which were derived from locally recurrent (14A and 14B) and metastatic (14C) tumors, lost all of 18q. However, in the other three cases, there was a partial loss of 18q in the recurrent or metastatic tumor cell lines but not in the primary tumor cell lines from the same patient. To determine whether the cell lines accurately reflect in vivo loss of 18q, we analyzed matched sets of normal, tumor, and tumor cell line DNA from eight patients with squamous cell carcinoma of the head and neck, including the tumor tissue corresponding to UM-SCC-81B. Three of the additional seven tumors and cell lines had 18q LOH. For all eight cases in which tumor and corresponding cell line DNAs were analyzed, there was complete concordance between allelic loss in the tumor and allelic loss in the corresponding cell line. The common region of loss established by tumors and cell lines with partial loss includes 18q21-18qter. This region contains the putative tumor suppressor gene DCC and two Mad (Mothers against dpp)-related genes, DPC4 and MADR2, which are both components in a transforming growth factor-beta-like signaling pathway. Loss of 18q in metastatic and locally recurrent tumors, but not in primary tumors from the same patients, suggests that a tumor suppressor gene in this region may be important in the progression of squamous cell carcinoma.

UM-EC-1, a new hypodiploid human cell line derived from a poorly differentiated endometrial cancer.

The University of Michigan endometrial carcinoma cell line UM-EC-1 was derived from a poorly differentiated endometrial adenocarcinoma of a 66-yr-old white female. Cell cultures were started using both tumor explants and a cell suspension obtained from collagenase-treated tumor tissue. The collagenase-derived cell suspension gave rise to monolayer cultures which grew rapidly from the outset. This subline of UM-EC-1 has now been subcultured more than 50 times. Cells derived from the tumor explants grew more slowly initially, but after a lag phase of 5 to 6 wk, this subline also exhibited rapid logarithmic growth and reached the same growth rate as that of the collagenase-treated cells. The explant subline has been subcultured more than 37 times. The doubling time of both sublines is 24 h under optimal growth conditions. The karyotype of both cell cultures is 43, XX, inv(1)(p32q42), -4, +der(8) t(8;12)(p23.1;q22), del(9)(q11), -13, -13, +t(13;13) (p13;p13), del(18)(q), -19, -22, -22, +t(22;22)(p11;p11). The net result of the chromosome losses and rearrangements was monosomy 4, duplication 8p23.1----qter, deletion 9q11----9qter, duplication 12q22----qter, deletion 18q, and monosomy 19. The t(13;13) and the t(22;22) were dicentric by C-banding. Virtually all of the chromosome changes were stable in multiple passages except that there was mosaicism for chromosome 13. Some cells contained a single copy of 13 and others had t(13;13). The available evidence indicates the t(13;13) is an isochromosome. UM-EC-1 cells produced tumors histologically similar to the original tumor in male, female, and ovariectomized female athymic mice. UM-EC-1 cells express human class I histocompatibility antigens as assessed by binding of antibodies to nonpolymorphic HLA and beta-2-microglobulin antigens. Blood group antigens A and H were absent although the patient is blood type A and these antigens are normally expressed in endometrial glands. A rearrangement involving the region of chromosome nine that carries the ABH locus may be related to the absence of blood group antigen expression by these cells. The E7 membrane antigen, the locus for which resides on the short arm of chromosome 11, was expressed strongly which is consistent with the presence of two intact copies of chromosome 11 in these cells.

Retrotympanic odontoma.

The clinical and histologic features of the second reported case of retrotympanic odontoma, which clinically presented as a cholesteatoma, are described. Origin from the posterior extension of the dental lamina is postulated. The dental lamina, the thickened oral ectoderm which outlines dental structures, is incorporated subendodermally in the lateral outpouching of the first pharyngeal pouch which produces the middle ear cavity. Histologically the odontoma was "complex," containing a haphazard arrangement of cementum, dentin, dental follicle and proliferating dental lamina, without the formation of recognizable teeth.

Detection of cryptococcal antigen. Comparison of two latex agglutination tests.

The detection of cryptococcal antigen by means of the agglutination of antibody-coated latex particles is an important aid in the diagnosis of cryptococcosis. A commercially available latex agglutination test (IBL kit) was compared with the latex agglutination test from the Center for Disease Control in regard to sensitivity, specificity, and height of antigen titer. Over a 13-month period, 335 specimens were tested with both kits. There was one false-positive reaction with both kits (0.4%) and one false-negative reaction only with the CDC kit, among 18 patients who had meningitis or disseminated infection due to Cryptococcus neoformans. Sera from patients who had localized pulmonary cryptococcosis showed negative results with both kits. The antigen titers measured by the two kits were the same or within two dilutions in 22 of 26 specimens of cerebrospinal fluid or serum from patients who had proved cryptococcosis. Overall, the IBL kit compared favorably with the CDC kit for the detection of cryptococcal antigen in cerebrospinal fluid or serum.

Anisakis larval type I in fresh salmon.

Larval ascarid nematodes recently discovered in fresh salmon were identified as Anisakis larval Type I, this roundworm is the etiologic agent of anisakiasis, a parasitic disease characterized by eosinophilic granulomas affecting the human gastrointestinal tract. Infection may occur following ingestion of raw or poorly cooked fish. Patients generally present with an acute abdominal syndrome mimicking a wide variety of clinical conditions, thus creating a diagnostic dilemma. Unselected samples of fresh salmon tested by the University of Michigan Clinical Microbiology Laboratory and School of Public Health were all infected, the mean worm burden calculated as 79.3 larvae per kilogram of fish. The significance of this infection and the implications for morbidity in the United States are discussed.

Rapid method of MIC determinations utilizing tetrazolium reduction.

A rapid preliminary method of determining antibiotic susceptibilities of clinically isolated gram-negative fermentative organisms has been evaluated. The method utilizes tetrazolium dye reduction as a colorimetric indicator of bacterial growth. Tetrazolium dye reduction is incorporated into the standard Micro-Media MIC microdilution testing system and shortens the required incubation period from 15 to 18 hours to 4 hours. Parallel MIC determinations were made by the standard MIC method and by the rapid tetrazolium method. The test organisms included 218 gram-negative fermentative clinical isolates. The overall correlation between the standard and the rapid MIC methods was 93%. Of the 7% discordant results, 6.3% represented minor discrepancies and 0.7% represented major discrepancies. There were no very major discrepancies. The study concluded that the rapid tetrazolium MIC method is an accurate, low-cost, easily implemented method of preliminary antibiotic susceptibility testing for gram-negative fermentative organisms.

Flow cytometric analysis of DNA in diagnostic cytology.

Flow cytometric analysis of nuclear DNA content and cell surface immunologic phenotyping were used in the evaluation of cytologic samples obtained from four patients. In each sample, a lymphoid cell population was present, which was difficult to evaluate by traditional cytopathologic methods. In two of the cases, the flow cytometric demonstration of monoclonal populations of lymphoid cells characterized by abnormal amounts of nuclear DNA gave support to the cytologic interpretation of malignancy. In a third sample, a lymphoid cell population that could not be cytologically distinguished from malignant lymphoma cells of small lymphoid cell type was shown to be composed of euploid, polyclonal cells. In the fourth case, the demonstration of euploidy in morphologically distinctive cell populations was helpful in interpreting the fine-needle aspirate of the thyroid gland. The authors conclude that flow cytometry can be used to great advantage in the evaluation of cytologic samples as well as in predicting biologic behavior.

Olfactory neuroblastoma: a retrospective clinicopathologic study.

The clinical course of olfactory neuroblastoma was not predictable by histologic criteria. Local recurrences were common (62%) and were often treated with multiple surgical procedures and radiation therapy. Metastatic neoplasm occurred in 28% of the patients. The recurrence-free interval decreased in those patients treated with radiation therapy initially, compared with those who had surgery initially. It is justifiable with respect to this study to treat disease in stages A and B with surgery and to reserve radiation therapy for recurrence. Stage C disease should be treated with combined therapy. Craniofacial resection should be promoted.

Sphenoid sinus brown tumor, hypercalcemia, and blindness: an unusual presentation of primary hyperparathyroidism.

This is a first report of primary hyperparathyroidism (HPT) masquerading as a destructive fibrous sphenoid sinus "Brown tumor" associated with progressive blindness and hypercalcemia. Diagnosis of a Brown tumor was delayed despite serial computerized tomography of the head and repeated transnasal and transethmoid sphenoid biopsies demonstrating diffuse fibrosis. Only detection and medical evaluation of hypercalcemia, demonstrating elevation of both serum calcium and C-terminal parathyroid hormone with an elevated chloride/phosphate ratio, prompted neck exploration, thus confirming a solitary left superior parathyroid adenoma. Postoperative normocalcemia occurred synchronously with the return of light perception and the arrest of sphenoid sinus and parasellar erosion. Although maxillary Brown tumors of secondary HPT have been reported, this is the first report of osteitis fibrosa of the sphenoid sinus. Differential diagnosis of an erosive sphenoid lesion with cranial nerve dysfunction, exclusive of inflammatory or vascular disease, should include sarcoidosis, primary and metastatic sphenoid carcinoma, fibrous dysplasia, giant cell reparative granuloma, midline lethal granuloma, chordoma, and chondrosarcoma. Furthermore, the bony destructive lesions with concomitant hypercalcemia of sarcoidosis and HPT are distinguishable by radiographic and laboratory analyses and by the Dent corticosteroid suppression test. Hypercalcemia of primary HPT is associated with elevated serum C-terminal parathormone, osteitis fibrosa, a negative Dent test, and a chloride/phosphate ratio greater than 33 in 94% of primary HPT patients. Hypercalcemia of sarcoidosis is associated with a normal or decreased C-terminal parathormone assay and a positive Dent test, as well as elevated serum immunoglobulins and erythrocyte sedimentation rate, and a positive angiotensin-converting enzyme assay.(ABSTRACT TRUNCATED AT 250 WORDS)

Manifestations and management of laryngoceles.

Six cases of laryngocele are reported including 2 bilateral, external laryngoceles, 1 internal laryngocele associated with amyloidosis, and 3 combined laryngoceles. Laryngoceles occur predominantly in males. Cervical mass and hoarseness were the most common signs and symptoms. Bilateral, external laryngoceles that decompress spontaneously when intralaryngeal air pressure returns to normal were managed conservatively. Combined and internal laryngoceles should be removed surgically through an external, lateral neck approach. This approach is preferable to anterior laryngofissure because it avoids trauma to the anterior commissure and the true vocal cords. In addition, blunting of the anterior commissure and the risk of subglottic stenosis are avoided.

Small cell carcinoma of the head and neck.

Treatment methods for patients with small cell carcinoma of the head and neck are changing. Increasing clinical experience with these tumors and a better appreciation of patterns of recurrence, the need for thorough tumor staging, and the importance of chemotherapy as a form of primary therapy have contributed to these changes. Current concepts regarding small cell carcinoma arising in the head and neck are reviewed. Reported results of treatment for a variety of head and neck sites and site-specific relapse rates are summarized. New cases of small cell carcinoma arising in the hypopharynx, paranasal sinus, and from an unknown primary are added to the reported experience in the literature.

Benign symmetrical lipomatosis (Madelung's disease).

Two patients with benign symmetrical lipomatosis (madelung's disease) have been followed for 7 and 9 years. Despite extensive surgical procedures, both patients have developed multiple recurrences. Lipomas and normal adipose tissue from the same patients were compared using chromatographic techniques. The lipomas contained significantly increased triglyceride fractions. Conservative surgical debulking is the recommended treatment.

Nasopharyngeal hamartoma: report of a case and review of the literature.

The uncommon benign developmental malformation, nasopharyngeal hamartoma, is reported with a review of the literature. Nasopharyngeal hamartoma can be divided into two types based on the histologic presentation. A more common type is composed predominantly of mesodermal tissues while a less common type, as reported in this study, is composed of a spectrum of mucosal epithelial, serous/mucinous gland, and stromal elements. Four additional cases of this less common type of nasopharyngeal hamartoma were found in the literature and are discussed with reference to age, sex, presenting symptoms, location, size, and histology.

Alveolar soft part sarcoma of the nasal cavity: report of a case and a review of the literature.

A case of alveolar soft part sarcoma of the nasal cavity is presented. Alveolar soft part sarcoma is a rare malignant neoplasm, which often affects females (ratio 2 to 1) in their second decade. It occurs most frequently in the extremities, with an unusual predilection to involve the right side of the body. Excluding the orbit, only a few cases have been reported in the head and neck area. We present the first reported case of alveolar soft part sarcoma limited to the nasal chamber.

Intralabyrinthine schwannoma.

The diagnosis of intralabyrinthine schwannoma has been made either accidentally at the time of surgery or at postmortem examination. Brain stem evoked response audiometry and computerized tomography do not add to our ability to make this diagnosis clinically. A case is presented of an intralabyrinthine schwannoma found at the time of transmastoid labyrinthectomy. The literature is reviewed and a composite clinical picture is presented.

Carcinoma in papillary cystadenoma lymphomatosum (Warthin's tumor).

Compared to the number of reported cases of a papillary cystadenoma lymphomatosum, malignant transformation is a rare event. This paper presents the third documented case of squamous cell carcinoma arising in the papillary cystadenoma lymphomatosum in a lymph node of the parotid region. Review of the American literature reveals 5 other cases of malignant transformation of papillary cystadenoma lymphomatosum including two cases of adenocarcinoma and one case of mucoepidermoid carcinoma with an apparent low potential for metastatic spread.

Chondrosarcoma of the head and neck.

Chondrosarcoma is a malignancy rarely encountered in the head and neck. In an attempt to define this tumor's characteristics and response to therapy, all cases of chondrosarcoma treated at the University of Michigan over the past 25 years were retrospectively studied. Fourteen cases originating in the nose and paranasal sinuses, mandible, temporal bone, and larynx were reviewed. Aggressive surgical resection was the mainstay of treatment, and resulted in an overall survival of 70%, with an average follow-up of 3.5 years. Survival was highest in primary temporal bone lesions, and lowest in paranasal sinus lesions. Unresectable lesions were not cured by other modalities. This study, therefore, continued to support the crucial role of wide surgical resection in the treatment of head and neck chondrosarcoma, but conservative resection, when needed to preserve important structures, has resulted in long-term survival.

Utilizing angiogenic agents to expedite the neovascularization process in skin flaps.

The revascularization of a skin flap after flap transposition is an important step in flap survival. This study investigates the efficacy of certain angiogenic agents to expedite the neovascularization process and to increase the viability of skin flaps. Eighty-four island skin flaps were designed on the auricles of 42 New Zealand White rabbits to achieve 90% necrosis over a 7-day period. Thirty-six flaps were treated with Endothelial Cell Growth Supplement (ECGS) or Endothelial Cell Growth Factor (ECGF) at several concentrations topically or immersed in Gelfoam. The remaining flaps were used as normal saline controls. Flap viability and peripheral neovascularization were documented by polar planimetry, angiography, and histological analysis. The flap viability of the ECGS-Gelfoam -treated flaps was 100% greater than their normal saline-Gelfoam controls (p = .021). Flap angiograms demonstrated increased vascular ingrowth among the treated flaps compared to the controls. This study suggests that angiogenic agents can expedite flap neovascularization and have the potential to increase flap viability.