Polymorphic reticulosis limited to the upper aerodigestive tract--natural history and radiotherapeutic considerations.

Polymorphic reticulosis (PMR) is a specific clinicopathological entity which commonly presents as an aggressive, necrotizing lesion of the upper airway. It is a separate nosologic entity from Wegener's granulomatosis, though its site and aggressive nature has lead to confusion in the distinction between these two different processes. Although radiotherapy has been acknowledged as the treatment of choice for limited upper airway PMR, little data exist to guide the radiation oncologist in the practical management of this disorder. We review our single institutional experience with PMR limited to the upper airway. Thirty-four patients (24 males, 10 females) with a median age of 44 years (range 19-80 years) are presented. Symptoms of nasal obstruction were present in 94%. Systemic symptoms such as fever, night sweats, and weight loss were noted in 62% and were often striking clinically. The nasal mucosa was most frequently involved (91%), although involvement of the paranasal sinuses (47%), palate (32%), as well as, other upper airway sites was not uncommon. Perforation of involved structures was recorded in 37%. All but 1 patient were treated with primary radiotherapy. Twelve relapsed with PMR and 3 additional patients manifested diffuse histiocytic lymphoma either within or adjacent to the original treatment field. The median survival relapse in these 15 patients was only 4 months, although 25% were salvaged at 5 years post-relapse. The overwhelming majority of relapses were noted within the first 3 years following treatment. An evaluation of radiotherapy parameters indicated that a minimum dose of 42 Gy or a TDF of 70 is necessary to achieve long-term local control. Pattern of failure analysis demonstrated in-field failure as the predominant failure site, and this problem should become much less significant with implementation of proper time-dose-fractionation schemes. Marginal failure was noted in 20% as a component of eventual failure sites suggesting the need for generous treatment volumes including clinically uninvolved adjacent structures at risk, such as palate, sinuses, and nasopharynx for nasal lesions. Finally, systemic failure occurred in 25%. Although this rate may be reduced by improved local treatment measures, ultimately effective systemic chemotherapy will be required to substantially impact on these patients' survival.

Postoperative adjuvant therapy of rectal cancer: an analysis of disease control, survival, and prognostic factors.

Between 1976 and 1984, 139 patients with rectal cancer were treated with complete surgical resection and postoperative adjuvant pelvic radiation therapy with or without chemotherapy. In this group, tumor extended beyond the bowel wall or involved lymph nodes or both. Irradiation was begun between 15 and 182 days postoperatively (median delay, 42 days). The radiation was delivered with 4-, 6-, or 10-MV photons given 5 days per week at 1.8 to 2.0 Gy per fraction. Total doses ranged from 3.8 to 64.4 Gy (median, 50 Gy). The fields were AP:PA in 49 and AP:PA plus laterals in 90. Forty-four received concurrent chemotherapy: 5-fluorouracil and semustine in 37, and 5-fluorouracil alone in seven. Follow-up in survivors ranged from 2 to 10 years (median, 4.2 years). This analysis includes all failures, both initial and subsequent sites of failure. Local failure occurred in 30 (22%) of the 139 patients overall, 6 (18%) of 33 in Stage B-2, 1 of 3 in Stage B-3, 2 (10%) of 20 in Stage C-1, 20 (26%) of 76 in Stage C-2, and 1 (14%) of 7 in Stage C-3. Five-year actuarial survival was 59% overall, 82% in Stage B-2, 79% in Stages B-2 and B-3, 89% in Stage C-1, 41% in Stage C-2, and 42% in Stages C-2 C-3. The following prognostic factors were independently associated with poorer survival and increasing distant failure: lymph node involvement, tumor extension beyond the bowel wall, and high histologic grade. Use of chemotherapy was associated with a significant improvement in survival and decrease in distant failure. No single factor was significantly associated with local failure. Adequate perineal coverage after combined abdominoperineal resection yielded significantly fewer perineal failures. Overall, serious complications developed in 7%, but none was fatal. Treatment recommendations and optimal treatment techniques are discussed.

Tumefactive fibro-inflammatory lesions of the head and neck.

Seven patients had tumefactive inflammatory fibrous lesions of the head similar in histologic appearance to Riedel's thyroiditis, sclerosing mediastinitis, and retroperitoneal fibrosis. Five patients were females, and the mean age at presentation was 48 years. Four patients presented clinically with a mass. Histologically, these lesions were characterized by an admixture of mature fibrous tissue and an inflammatory infiltrate of lymphocytes and scattered polymorphonuclear leukocytes. Initially, all patients had been treated surgically. Two patients received radiation therapy when recurrent disease could not be controlled surgically. Five of the six patients on whom follow-up information was available were alive at follow-up that ranged from 14 to 49 months (mean 29). These lesions are distinct histologically from desmoid tumors, fibromatoses, and nodular fasciitis. The spectrum of fibrosclerosing lesions (Riedel's thyroiditis, idiopathic mediastinal fibrosis, retroperitoneal fibrosis, and sclerosing cholangitis) probably includes this group of tumefactive inflammatory fibrous lesions of the head.

Mucous membrane plasmacytosis of the upper aerodigestive tract. A clinicopathologic study.

We report 9 patients with an unusual plasma cell proliferative disorder of the upper aerodigestive tract. Six patients were men and three, women. The age at presentation ranged from 40 to 67 years with a mean of 54 years. Symptoms at presentation included dysphonia, dysphagia, difficulty breathing, and oral pain. These plasma cell lesions typically produced a cobblestone or warty appearance of the upper aerodigestive tract mucosa including the larynx, pharynx, palate, lips, mouth, tongue, and trachea in varying combination of multiple sites in each patient. Histologically, all lesions were characterized by psoriasiform epithelial hyperplasia with dyskeratosis and dense subepithelial plasmacytosis. Plasma cells were mature but so expansive and diffuse in infiltration as to suggest extramedullary plasmacytoma. Immunohistochemistry for kappa and lambda light chain showed polyclonal immunoglobulin content in all cases examined. Microbial cultures and Warthin-Starry stains were negative for organisms. A variety of treatments including antibiotic therapy, corticosteroid administration, and surgical resection were unsuccessful. In two patients, the process required tracheostomy. This disorder has not been previously described with the exception of a single reported case, which is included in this series. The etiology, pathogenesis, and successful management of mucous membrane plasmacytosis remain unknown.

Primary thymic carcinomas.

Within a 75-year period, 20 patients with primary nonteratomatous carcinomas of the thymus were seen at the Mayo Clinic. Fourteen were males and six were females, with a mean age of 48 years. Thirteen of the lesions were classified as poorly differentiated or spindling squamous cell carcinomas. One neoplasm was a sarcomatoid carcinoma, and two showed both squamous cell and neuroendocrine ultrastructural features. The remaining four tumors had both light- and electron-microscopic features of neuroendocrine carcinomas. In all 20 patients, careful clinical and pathologic examinations, including autopsy in fatal cases, excluded malignant lymphomas and metastasis to the thymus from epithelial tumors in other anatomic sites. Thirteen patients underwent surgery, with or without postoperative radiotherapy; of these, one was alive and apparently disease-free 43 months after diagnosis. There were two operative deaths. The remaining patients received primary radiotherapy or chemotherapy, or both. The mean survival of the 16 patients who died (excluding operative deaths) was 18.7 months for the 14 patients with tumors of squamous cell differentiation and 36.0 months for the two patients with pure neuroendocrine carcinomas. Among patients with squamous cell carcinoma, 11 developed metastases to lungs, liver, bones, adrenal glands, or extrathoracic lymph nodes; nine of these died of massive local growth within the mediastinum. Among patients with neuroendocrine carcinomas, two of four patients died of local growth within the mediastinum; one of these also had metastases to the liver and adrenal glands. One patient with oat cell carcinoma was alive with residual thoracic tumor and cervical lymph node metastasis 18 months after diagnosis.

Lipoadenoma of the parathyroid gland.

An unusual parathyroid adenoma containing abundant adipose tissue is described in four patients. In one patient, hyperparathyroidism was documented; in another, studies were incomplete but the adenoma was probably functioning. Prior reports of similar lesions have been called "parathyroid hamartoma or parathyroid adenoma with myxoid stroma," and some of these also have been shown to be functional. They may create diagnostic difficulties because of the presence of adipose tissue, a feature associated with normal parathyroid glands.

Trends in colorectal cancer over a half century in Rochester, Minnesota, 1940 to 1989.

Recent reports of increasing incidence, especially in men, led us to update through 1989 an earlier study of colorectal cancer incidence in Rochester that covered the period 1940 through 1979. The combined data reflected cancer trends in the community over half a century. Data resources of the Rochester Epidemiology Project were used to identify new cases of colon and rectal cancer among Rochester residents. Incidence rates were estimated using decennial census data, and 95% confidence intervals were based on the Poisson distribution. The GLIM statistical package was used to evaluate trends over time. Age-adjusted (US white 1970) incidence rates of colorectal cancer for men were 53.7, 61.3, 53.7, 54.2, and 52.5 per 100,000 person-years, respectively, for the decades 1940 to 1949, 1950 to 1959, 1960 to 1969, 1970 to 1979, and 1980 to 1989. Comparable rates for women were 42.7, 49.3, 42.9, 40.7, and 40.9 per 100,000 person-years. No statistically significant changes were seen in the incidence of colon and rectum cancer for men or women. There was no consistent trend in tumor stage at diagnosis and the mean size of the initial lesion did not change with time. The incidence of colorectal cancer has not changed over the past 50 years in this community where case ascertainment has been consistent and complete.

Polymorphic reticulosis, lymphomatoid granulomatosis. Two diseases or one?

Clinical and pathologic data on 40 patients (31 men, 9 women) with polymorphic reticulosis are presented. The disease may involve the upper respiratory tract, notably the nose, paranasal sinuses, nasopharynx, or palate, as well as the lung, skin, gastrointestinal tract, and central nervous system. Polymorphic reticulosis is identical pathologically to lymphomatoid granulomatosis. Localized disease, particularly that in the upper airway, responds well to radiation therapy. Corticosteroids and cytotoxic agents appear to be ineffective with multisite involvement.

Respiratory vasculitis.

Respiratory vasculitis is characterized by granulomatous changes pathologically. Both upper and lower respiratory tracts may be involved. It is convenient to separate three entities: (1) Wegener's granulomatosis, (2) allergic granulomatosis and angiitis, or Churg-Strauss syndrome, and (3) polymorphic reticulosis/lymphomatoid granulomatosis complex. Churg-Strauss syndrome responds well to glucocorticoids. Cytotoxic drugs appear necessary for ultimate control of Wegener's granulomatosis. Radiation therapy is effective in controlling polymorphic reticulosis/lymphomatoid granulomatosis when it is localized to one site. Evidence suggests that polymorphic reticulosis/lymphomatoid granulomatosis may be closely related to lymphoproliferative disorders.

Correlation of histopathologic characteristics of primary tumor and uninvolved regional lymph nodes in Dukes' class C colonic carcinoma with prognosis.

Ninety-two patients with Dukes' class C colonic carcinoma, divided equally into those who survived 5 years or more and those surviving less than 5 years after resection for cure, underwent evaluation of multiple histopathologic characteristics of the primary tumor and the uninvolved regional lymph nodes. These characteristics were analyzed by the chi-square test for correlation with survival. A statistically significant correlation (P less than 0.05) in the group who survived 5 years or more was observed for Broders' grades 1 and 2, tumor not involving serosa, and a pushing tumor margin. Of the 14 patients who had a pushing tumor margin and tumor not involving serosa, 12 (86%) survived 5 years or more. Seven patients had an infiltrating tumor margin and peritumor venous invasion, and of this group, only one (14%) survived 5 years or more. Histopathologic characteristics of host immune reaction at the tumor or in the uninvolved regional lymph nodes did not correlate with survival.

Endoscopic gastric polypectomies.

Results of 48 consecutive endoscopic gastric polypectomies were reviewed. The most frequent complaint initiating diagnostic workup was epigastric discomfort. Hyperplastic polyps predominated, followed by adenomatous polyps, carcinoids, and other. Two adenomatous polyps contained foci of in situ malignant change. The low incidence of malignant change in adenomatous polyps (17%) can be accounted for by the smaller size (mean 1.4 cm) than that in other reports. No malignancy was found in or in conjunction with hyperplastic site (two) and poor patient compliance (one)--and no deaths. Endoscopic gastric polypectomy has been demonstrated to be a safe and effective therapy for gastric polyps. For adenomatous gastric polyps, endoscopic removal when the polyp is less than 2 cm in diameter will yield a low incidence of malignant change.

Angioimmunoblastic lymphadenopathy.

Forteen cases of angioimmunoblastic lymphadenopathy were reviewed retrospectively, and histologic material was examined by various staining and histochemical techniques. The predominant morphologic features were effacement of nodal architecture, microvascular proliferation, and a polymorphous cellular infiltrate of immunoblasts, plasma cells, lymphocytes, and eosinophils. Immunofluorescence studies suggested the presence of cells elaborating a variety of immune globulins with an unpredictable pattern. The clinical course and treatment varied, perhaps partly reflecting the initial spectrum of diagnoses made in these cases before angioimmunoblastic lymphadenopathy was defined. Because systemic infection appears to be a major factor in the deaths of these patients whose immune competence is uncertain, the usual chemotherapy for malignant lymphomas may be too vigorous for this condition. At present, the cause of the condition is unknown.

Massive bleeding from a ruptured metastatic hepatic melanoma treated by hepatic lobectomy. Case report and review of the literature.

An unusual case is reported of an occult, spontaneously rupturing, hemorrhagic, metastatic melanoma of the liver treated by hepatic lobectomy, resulting in short-term survival. A long, symptom-free interval (13 years) after excision of the primary cutaneous lesion (stage I) preceded the appearance of the hepatic metastasis. This case illustrates the need for a careful and thorough history as well as the benefit of prompt hepatic resection for bleeding from ruptured hepatic malignancies.

Wegener's granulomatosis: observations on treatment with antimicrobial agents.

Twelve patients with Wegener's granulomatosis were treated with antimicrobial agents, chiefly trimethoprim-sulfamethoxazole. The clinical course improved in 11 of the 12 patients who received this treatment. The success of antimicrobial treatment suggests the possibility of a microbial infection as the inciting cause of Wegener's granulomatosis in some patients. Alternatively, these agents--in particular, trimethoprim-sulfamethoxazole--may possess immunosuppressant activity.

Benign lymphocytic angiitis and granulomatosis: experience with three cases.

Of three patients with lung-biopsy-proven benign lymphocytic angiitis and granulomatosis, two experienced complete resolution of their disease from therapy with chlorambucil and one underwent spontaneous remission with no drug therapy after lung biopsy and removal of a benign spindle cell thymoma. Clinically, it is difficult to determine whether benign lymphocytic angiitis is a low-grade (prelymphomatous) lymphoma or a vasculitis. Its position in this spectrum of diseases is uncertain. Nonetheless, benign lymphocytic angiitis and granulomatosis corresponding to a low-grade angiocentric immunoproliferative lesion is a clinicopathologically useful concept.

Increasing incidence of pancreatic cancer among women in Olmsted County, Minnesota, 1940 through 1988.

To determine trends in the incidence of pancreatic cancer and associated survival, we conducted a population-based study in Olmsted County, Minnesota. From 1940 through 1988, 219 residents of Olmsted County (120 men and 99 women) were diagnosed as having exocrine pancreatic cancer. All patients were Caucasians, and 92% had a histologically confirmed diagnosis. The mean annual adjusted incidence of pancreatic cancer per 100,000 population was 8.5 overall (11.3 for men and 6.6 for women). During the course of the study, the incidence rates increased in women (P < 0.05) and in both genders combined (P = 0.06) but not in men (P = 0.4). The male:female ratio decreased from approximately 2:1 for 1940 through 1949 to 1.5:1 for 1980 through 1988. The incidence was significantly associated with increasing age (P < 0.001) and male gender (P < 0.001) but not calendar period (P = 0.19). The overall median duration of survival was 2.8 months. The 1-year survival rate was only 14%, and no patient lived for more than 55 months after pancreatic cancer was diagnosed. Men and women had similar survival rates. The increased incidence of pancreatic cancer among women may be due in part to the increasing life span of women and the increasing occurrence of pancreatic cancer in the aged.

Carcinosarcoma of the lung: Mayo Clinic experience and response to chemotherapy.

The clinical presentation, clinical course, and results of various treatment modalities of 17 patients with carcinosarcoma of the lung were reviewed. This group of patients was 0.2% of all Mayo Clinic patients with lung cancer who had been treated between 1971 and 1982. Most patients were men in the sixth decade of life who had a history of smoking. Ten of 17 neoplasms were located in the upper lobes. Noninvasive diagnostic tests had a low yield in detecting carcinosarcomas. Pulmonary resection with curative intent was performed in 15 of 17 patients; however, only 4 patients were alive at 6, 8, 28, and 39 months, respectively, postoperatively. The median survival was 1 year. Doxorubicin-based chemotherapeutic programs produced an objective response in two of four patients.

Ceroidosis in the "brown bowel syndrome".

A middle-aged patient with "brown bowel syndrome" or gastrointestinal ceroidosis manifested as malabsorption of undetermined cause is described. Autopsy revealed involvement of the entire gastrointestinal tract and unusual cardiac findings. Microscopically, the pigment responsible for the discoloration is a lipofuchsin that is deposited in the smooth muscle cells of the gastrointestinal tract. In all reported cases, ceroidosis was associated with some abnormality of the gastrointestinal tract--that is, malabsorption, steatorrhea, or gross local disease--with the possible exception of prolonged malnutrition. This case is also unusual because of the unexplained multifocal proliferative endocarditis. Vitamin E deficiency may be the common denominator of all these various disorders.

Limited thoracotomy in the pediatric patient.

Thirty-one children underwent 33 limited thoracotomies between 1973 and 1979. Adequate tissue for diagnosis was obtained in each case, and subsequent therapy was influenced in 91%. The preoperative diagnosis was confirmed in 61% and corrected in 36%. One death may have been hastened by the procedure, but all others were related to the underlying disease process. There were very few complications, the most common being pneumothorax. The routine use of a chest tube postoperatively seems to reduce the frequency of pneumothoraces. The average duration of the operation was 50 minutes. We believe that limited thoracotomy is a safe and rapid method of obtaining lung tissue and almost always ensures adequate tissue for diagnosis.

Flow cytometric DNA patterns from colorectal cancers--how reproducible are they?

The heterogeneity of DNA ploidy patterns within individual colorectal carcinomas was investigated by analyzing 261 different samples from 30 fresh colorectal cancers. The results of DNA analysis of multiple superficial cup biopsy specimens, of multiple full-thickness fresh tumor slices, and of nuclei extracted from paraffin-embedded pathologic archival specimens with use of the Hedley technique were compared. The same DNA ploidy pattern was found in all specimens of 19 (63%) of the 30 tumors studied. Minimal heterogeneity for DNA ploidy pattern was noted in seven carcinomas (23%), and moderate to marked heterogeneity was found in an additional four tumors (13%). The DNA pattern of a full-thickness specimen from 79% of the carcinomas studied was the same when samples were obtained from any one of five possible sites. In addition, the DNA ploidy pattern of the majority of the carcinomas could have been accurately predicted by flow cytometric DNA analysis of superficial cup biopsy specimens. These results demonstrate that most colorectal carcinomas are DNA ploidy homogeneous. Therefore, measurement of this tumor property can be used in future clinical research studies with some degree of confidence.