Hyun Y. Pak

Bronchopulmonary Kulchitzky cell carcinomas. A new classification scheme for typical and atypical carcinoids.

Typical and atypical carcinoids constitute less than 5% of lung tumors. They and small cell undifferentiated lung cancers (SCLC) belong to the same family of apudomas arising from bronchopul‐monary Kulchitzky cells. To reflect the overlap among these cancers, the authors suggest calling them Kulchitzky cell carcinomas (KCC); to indicate their spectrum of aggressiveness, the authors suggest calling typical carcinoids KCC‐I, atypical carcinoids KCC‐II, and small cell cancers KCC‐III. One hundred fifty‐six KCCs were reviewed: 115 were KCC‐I and 41 were KCC‐II. The ratio of women to men equals 2:1. At time of initial diagnosis, all patients with KCC‐I, except one patient, were in Stage I. Among patients with KCC‐II, 16 (39%) were in Stages II or III at time of presentation. The incidence of carcinoid syndrome was 1.9%. Treatment was lobectomy in 112 (72%) of patients, the remainder having lesser resections or pneumonectomy in approximately equal distribution. Our data cannot support the use of radical resection in the treatment of KCC because none of the patients died of local recurrence. The mean diameters of KCC‐I and ‐II tumors were 1.5 and 2.8 cm, respectively. Increased mitotic activity and tumor necrosis were reliable criteria for diagnosing KCC‐II. Electron microscopic examination did not help in differentiating KCC‐I and KCC‐II. Thorough sampling of the entire tumor was found to be mandatory for precise diagnosis and for differentiation from KCC‐III (SCLC). Measurement of nuclear DNA was done using integrated optical density (IOD) by image analysis. The IODs of KCC‐I, ‐II and ‐III were 1.36, 1.55 and 1.94, respectively. These significant differences (P < 0.001) correlated with the aggressiveness of the cancers. Of patients with KCC‐I, 1.7% succumbed to KCC; this included one patient reported to have died of KCC‐III (SCLC). Of 41 patients with KCC‐II, 11 (27%) died of KCC; this includes at least 3 deaths from KCC‐III. Cancer 55:1303‐1311, 1985.

Glassy cell carcinoma of the cervix cytologic and clinicopathologic analysis

A clinicopathologic analysis of 15 patients with glassy cell carcinoma confirmed that this is a rare disease, having an incidence of 1.2%. It is a rapidly progressive and biologically aggressive disease with early extrapelvic metastasis. The five‐year survival and the median survival in our series were 28% and 14 months, respectively. The majority of patients (87%) were understaged, which may have played a role in the poor prognosis. Four of 12 patients (33%) were initially diagnosed as having a benign disease (false‐negatives). Defining of cytologic characteristics and differential features of this tumor may facilitate an early and more accurate diagnosis to improve prognosis. Cancer 52:307‐312, 1983.

Hepatic metastasis in granulosa cell tumor of the ovary

Hepatic metastases occur rarely in epithelial ovarian carcinoma and also appear to be unusual in malignant stromal tumors of the ovary (granulosa cell tumors). Recently two patients with extensive hepatic metastasis from this primary tumor, were treated. Review of the experience at the City of Hope National Medical Center provided three additional patients with a confirmed diagnosis of granulosa cell tumor of the ovary, one of whom is alive and disease‐free. A review of clinical and pathologic data revealed that both of the other patients died of their disease and had hepatic metastases proven at autopsy. Hemorrhagic events complicating the clinical course of these patients were frequent. It is believed that the frequency of hepatic metastasis in granulosa cell tumor of the ovary may be higher than has been appreciated in the past, and that the cystic‐hemorrhagic nature of these lesions contributes to the morbidity and mortality associated with granulosa cell tumors of the ovary.

A Clinically Relevant Canine Lung Cancer Model

Research on early human lung cancer is difficult; we have sought a canine correlate. Regimens included endobronchial submucosal injections and topical focal applications of benzo[a]pyrene, nitrosomethylurea, dimethylbenzanthracene, and methylcholanthrene, singly or in combinations. Sustained-release discs were placed into lung parenchyma or sutured into major bronchi. Tracheal segments were isolated as cervical pedicle grafts. Gross and histological evolution was reproducible. Columnar and basal hyperplasia and squamous metaplasia were early changes. Atypia occurred within 6 weeks and was found in all dogs within 16 to 18 weeks. Invasive cancers occurred within 8 to 65 months. No tracheal graft developed cancer. Of 15 dogs with parenchymal sustained-release implants, 1 to date has developed cancer in 8 months. Four endobronchial regimens have produced 16 cancers in 56 lungs at risk for 18 to 65 months. No cancers developed in 23 lungs at risk from eight other regimens. Of 10 dogs at risk for unilateral endobronchial cancer, 5 have had cancer. Of 23 dogs with both lungs at risk, 9 developed cancer. We have shown focal carcinogenesis with well-defined pathogenesis and an extended preneoplastic period at predictable sites in a lung cancer model.

A Family of Epidermoid Lung Cancer Models

A method of sustained release implantation has been developed whereby Silastic cylinders, impregnated with benzo[alpha]pyrene (BP) or methylcholanthrene (MCA) each at 2% (low dose) and 10% (high dose) concentrations, were inserted into the bronchus intermedius of hamsters. High-dose BP and MCA, and low-dose MCA had first-order exponential release rates: the half-time of release was 40 days for high-dose BP, 30 days for high-dose MCA, and 165 days for low-dose MCA. Release rate of low-dose BP was a second-order function: half-time of release was 40 days. Atypical squamous metaplasia was noted by 4 weeks in more than 65% of hamsters after insertion of each high-dose carcinogen but in less than 30% with the low-dose carcinogens. Carcinoma in situ was noted approximately 8 weeks after high-dose BP and 19 weeks after low-dose BP. At about 15 to 17 weeks after a high-dose carcinogen, 64% of animals had invasive epidermoid cancer, whereas after a low-dose carcinogen, only 21% did. After 25 weeks of exposure to a high-dose carcinogen, more than 85% of hamsters had invasive epidermoid cancer; up to 52 weeks were required for invasive epidermoid cancer to develop in 30% after a low-dose carcinogen. Measured by image analysis, nuclear deoxyribonucleic acid content of cells with severe atypical squamous metaplasia was greater than tetraploid (mean +/- standard deviation [SD], 3.77 +/- 1.4), whereas cells with invasive epidermoid cancer were suprahexaploid (mean +/- SD, 6.48 +/- 3.6). These differences are significant (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Surgical management of lymphomas involving the chest

The efficacy of surgical judgments in the management of thoracic lymphoma was studied through review of 34 patients with primary mediastinal lymphomas, 30 patients who needed one or more thoracic operations after treatment of extrathoracic lymphomas, and 5 patients with primary lymphocytic infiltrates (PLI) of the lung. In all patients with primary lymphocytic infiltrates of the lung, thoracotomies were required in order to establish the correct diagnosis. Patients with primary mediastinal lymphoma required 74 surgical procedures (2.2 per patient) to establish the correct diagnosis. In retrospect, 40 operations were not beneficial. The procedures that provided diagnostic samples were 15 anterior mediastinotomies, 8 full thoracotomies, 3 median sternotomies, and 8 lesser procedures such as mediastinoscopy. Patients who needed thoracic procedures after treatment of extrathoracic lymphomas had 41 thoracic operations (1.37 per patient). Five operations were needed to manage complications of thoracic lymphoma or its therapy. To evaluate new radiographic findings, there were 35 operations (1.3 per patient) at a mean interval of 5.0 years following initial treatment; the findings were recurrent lymphoma in 62% and new lesions in 38% of patients. Among new lesions, there were 2 bronchogenic cancers; 9 enlarging mediastinal-pleural masses were not caused by lymphoma. The accurate diagnosis of thoracic lymphoma or new thoracic lesions in patients with lymphomas usually requires enough tissue for immunophenotyping. Providing adequate tissue samples and treating new lesions that are not lymphomas often require major thoracomediastinotomies for immunophenotyping.

Carcinogenesis in Canine Bistomal Heterotopic Tracheal Grafts

Successful canine lung cancer models have required repeated focal bronchial carcinogen exposure under general anesthesia. To simplify serial studies of the respiratory mucosa during carcinogenesis, bistomal autologous heterotopic tracheal pedicle grafts have been made. These grafts can readily be returned to the original orthotopic site, and this has been shown to be a method with which to study reversibility of mucosal changes. Polycyclic aromatic hydrocarbons were applied topically to the mucosa three times a week for 21 to 22 months in 21 grafts. Implants of Silastic polymer from which carcinogen was released in sustained-release fashion were then left in the grafts for 4 to 6 weeks. Serial cytological and histological examinations showed development of atypical squamous metaplasia in the graft mucosa. Mucosal papillomatosis was noted in 4 of 7 grafts surgically excised 17 to 18 months after completion of carcinogen exposure. The heterotopic bistomal tracheal graft provides a useful method for studying respiratory epithelial carcinogenesis without repeated general anesthesia.

Staging of Lung Carcinoma

Lung cancer is a continuum where in normal epithelial cells are progressively replaced by preneoplastic cells, and eventually by cancer cells. The patterns of spread are to local, regional and distant lymph nodes, and to organ systems like the liver, brain, bone and bone marrow. As illustrated by the fact that pericardial effusions and adrenal insufficiency may be consequences of metastatic bronchogenic carcinoma, there are no boundaries of spread.