Pathologic features of response to neoadjuvant anti-PD-1 in resected non-small-cell lung carcinoma: a proposal for quantitative immune-related pathologic response criteria (irPRC).

Background: Neoadjuvant anti-PD-1 may improve outcomes for patients with resectable NSCLC and provides a critical window for examining pathologic features associated with response. Resections showing major pathologic response to neoadjuvant therapy, defined as ≤10% residual viable tumor (RVT), may predict improved long-term patient outcome. However, %RVT calculations were developed in the context of chemotherapy (%cRVT). An immune-related %RVT (%irRVT) has yet to be developed. Patients and methods: The first trial of neoadjuvant anti-PD-1 (nivolumab, NCT02259621) was just reported. We analyzed hematoxylin and eosin-stained slides from the post-treatment resection specimens of the 20 patients with non-small-cell lung carcinoma who underwent definitive surgery. Pretreatment tumor biopsies and preresection radiographic 'tumor' measurements were also assessed. Results: We found that the regression bed (the area of immune-mediated tumor clearance) accounts for the previously noted discrepancy between CT imaging and pathologic assessment of residual tumor. The regression bed is characterized by (i) immune activation-dense tumor infiltrating lymphocytes with macrophages and tertiary lymphoid structures; (ii) massive tumor cell death-cholesterol clefts; and (iii) tissue repair-neovascularization and proliferative fibrosis (each feature enriched in major pathologic responders versus nonresponders, P < 0.05). This distinct constellation of histologic findings was not identified in any pretreatment specimens. Histopathologic features of the regression bed were used to develop 'Immune-Related Pathologic Response Criteria' (irPRC), and these criteria were shown to be reproducible amongst pathologists. Specifically, %irRVT had improved interobserver consistency compared with %cRVT [median per-case %RVT variability 5% (0%-29%) versus 10% (0%-58%), P = 0.007] and a twofold decrease in median standard deviation across pathologists within a sample (4.6 versus 2.2, P = 0.002). Conclusions: irPRC may be used to standardize pathologic assessment of immunotherapeutic efficacy. Long-term follow-up is needed to determine irPRC reliability as a surrogate for recurrence-free and overall survival.

Radiologic findings in a patient with frontal parafalcine dendritic cell histiocytoma.

We report the case history and radiologic findings of a patient with a biopsy-proven dendritic cell histiocytoma presenting as a single intracranial extra-axial mass and no systemic disease. Even though this entity is relatively rare, it should nevertheless be considered in the differential diagnosis of dural-based space-occupying central nervous system lesions.

Alpha-Tocopherol and beta-carotene supplements and lung cancer incidence in the alpha-tocopherol, beta-carotene cancer prevention study: effects of base-line characteristics and study compliance.

BACKGROUND: Experimental and epidemiologic investigations suggest that alpha-tocopherol (the most prevalent chemical form of vitamin E found in vegetable oils, seeds, grains, nuts, and other foods) and beta-carotene (a plant pigment and major precursor of vitamin A found in many yellow, orange, and dark-green, leafy vegetables and some fruit) might reduce the risk of cancer, particularly lung cancer. The initial findings of the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (ATBC Study) indicated, however, that lung cancer incidence was increased among participants who received beta-carotene as a supplement. Similar results were recently reported by the Beta-Carotene and Retinol Efficacy Trial (CARET), which tested a combination of beta-carotene and vitamin A. PURPOSE: We examined the effects of alpha-tocopherol and beta-carotene supplementation on the incidence of lung cancer across subgroups of participants in the ATBC Study defined by base-line characteristics (e.g., age, number of cigarettes smoked, dietary or serum vitamin status, and alcohol consumption), by study compliance, and in relation to clinical factors, such as disease stage and histologic type. Our primary purpose was to determine whether the pattern of intervention effects across subgroups could facilitate further interpretation of the main ATBC Study results and shed light on potential mechanisms of action and relevance to other populations. METHODS: A total of 29,133 men aged 50-69 years who smoked five or more cigarettes daily were randomly assigned to receive alpha-tocopherol (50 mg), beta-carotene (20 mg), alpha-tocopherol and beta-carotene, or a placebo daily for 5-8 years (median, 6.1 years). Data regarding smoking and other risk factors for lung cancer and dietary factors were obtained at study entry, along with measurements of serum levels of alpha-tocopherol and beta-carotene. Incident cases of lung cancer (n = 894) were identified through the Finnish Cancer Registry and death certificates. Each lung cancer diagnosis was independently confirmed, and histology or cytology was available for 94% of the cases. Intervention effects were evaluated by use of survival analysis and proportional hazards models. All P values were derived from two-sided statistical tests. RESULTS: No overall effect was observed for lung cancer from alpha-tocopherol supplementation (relative risk [RR] = 0.99; 95% confidence interval [CI] = 0.87-1.13; P = .86, logrank test). beta-Carotene supplementation was associated with increased lung cancer risk (RR = 1.16; 95% CI = 1.02-1.33; P = .02, logrank test). The beta-carotene effect appeared stronger, but not substantially different, in participants who smoked at least 20 cigarettes daily (RR = 1.25; 95% CI = 1.07-1.46) compared with those who smoked five to 19 cigarettes daily (RR = 0.97; 95% CI = 0.76-1.23) and in those with a higher alcohol intake (> or = 11 g of ethanol/day [just under one drink per day]; RR = 1.35; 95% CI = 1.01-1.81) compared with those with a lower intake (RR = 1.03; 95% CI = 0.85-1.24). CONCLUSIONS: Supplementation with alpha-tocopherol or beta-carotene does not prevent lung cancer in older men who smoke. beta-Carotene supplementation at pharmacologic levels may modestly increase lung cancer incidence in cigarette smokers, and this effect may be associated with heavier smoking and higher alcohol intake. IMPLICATIONS: While the most direct way to reduce lung cancer risk is not to smoke tobacco, smokers should avoid high-dose beta-carotene supplementation.

K-ras oncogene activation in atypical alveolar hyperplasias of the human lung.

Atypical alveolar hyperplasia (AAH) is a potential precursor lesion from which lung adenocarcinomas arise and may be a good target for studying the early events of lung tumorigenesis. A common genetic alteration in lung adenocarcinomas is mutational activation of K-ras. To determine the timing of K-ras activation, we evaluated formalin-fixed and paraffin-embedded tissue samples of 41 AAHs and their paired lung neoplasms from 28 patients for codon 12 point mutations of the K-ras oncogene. K-ras codon 12 mutations were detected using PCR followed by allele-specific oligonucleotide hybridization. Mutations were found in 16 (39%) of the 41 AAHs, 8 (42%) of the 18 adenocarcinomas, and none (0%) of the 5 lung neoplasms that were not adenocarcinomas. Of the 18 patients with both an AAH and a synchronous lung adenocarcinoma, 6 had K-ras mutation in the adenocarcinoma but not in the AAH, 6 had mutations in the AAH but not in the adenocarcinoma, 4 did not harbor mutations in either the AAH or the adenocarcinoma, and 2 had mutations in both their AAH and their synchronous adenocarcinoma. In just 1 of the 18 patients was the same K-ras mutation present in the AAHs and adenocarcinoma of the patient. The detection of independent activating point mutations in a cancer-causing gene points to the neoplastic nature of AAH and suggests that glandular neoplasms of the lung arise from a background of field cancerization.

Multimodal therapy for the management of localized Ewing's sarcoma of pelvic and sacral bones: a report from the second intergroup study.

A total of 59 eligible patients with localized Ewing's sarcoma of the pelvic and sacral bones were entered into a multimodal Intergroup Ewing's Sarcoma Study (IESS-II) (1978 to 1982) and compared with a historical control series of 68 patients entered into an earlier multimodal Intergroup Ewing's Sarcoma Study (IESS-I) (1973 to 1978). High-dose intermittent multiagent chemotherapy (vincristine, cyclophosphamide, Adriamycin [doxorubicin; Adria Laboratories, Columbus, OH], and dactinomycin) was given to all patients for 6 weeks before and for 70 weeks following local therapy. All patients who had a tumor biopsy or incomplete resection performed received a dose of 55 Gy to the tumor bed. With a median follow-up time of 5.5 years, two of 59 patients (3%) had a local recurrence, five patients (8%) had a local recurrence and metastases, and 17 patients (29%) developed metastases only. There was significant statistical evidence of an advantage in relapse-free survival (RFS) and survival (S) for patients on IESS-II versus IESS-I, P = .006 and P = .002, respectively. At 5 years, the comparison between IESS-II versus IESS-I was 55% versus 23% for RFS and 63% versus 35% for S.

Multimodal therapy for the management of primary, nonmetastatic Ewing's sarcoma of bone: a long-term follow-up of the First Intergroup study.

A total of 342 previously untreated eligible children were entered into the first Intergroup Ewing's Sarcoma Study (IESS) between May 1973 and November 1978. In group I institutions, patients were randomized between treatment 1 (radiotherapy to primary lesion plus cyclophosphamide, vincristine, dactinomycin, and Adriamycin [doxorubicin; Adria Laboratories, Columbus, OH] [VAC plus ADR]) or treatment 2 (same as treatment 1 without ADR), and group II institutions randomized patients between treatment 2 or treatment 3 (same as treatment 2 plus bilateral pulmonary radiotherapy [VAC plus BPR]). The percentages of patients relapse-free and surviving (RFS) at 5 years for treatments 1, 2, and 3 were 60%, 24%, and 44%, respectively. There was strong statistical evidence of a significant advantage in RFS for treatment 1 (VAC plus ADR) versus 2 (VAC alone) (P less than .001) and 3 (P less than .05) and also of treatment 3 versus 2 (P less than .001). Similar significant results were observed with respect to overall survival. Patients with disease at pelvic sites have significantly poorer survival at 5 years than those with disease at nonpelvic sites (34% v 57%; P less than .001). Among pelvic cases, there was no evidence of differing survival by treatment (P = .81), but among nonpelvic cases, there was strong evidence of differing survival by treatment (P less than .001). The overall percentage of patients developing metastatic disease was 44%; the percentages by treatments 1, 2, and 3 were 30%, 72%, and 42%, respectively. The overall incidence of local recurrence was 15%, and there was no evidence that local recurrence rate differed by treatment. Patient characteristics related to prognosis, both with respect to RFS and overall survival experience, were primary site (nonpelvic patients were most favorable) and patient age (younger patients were more favorable).

Ewing's sarcoma in bones of the hands and feet: a clinicopathologic study and review of the literature.

Review of current data from the Intergroup Ewing's Sarcoma Study (IESS) shows that Ewing's sarcoma (ES) is rare in bones of the hands and feet. Only 12 of 377 evaluable patients in the first two IESS studies had a primary tumor in these small, distal bones. The age distribution was typical for that seen in patients with ES at other sites. Males were affected twice as often as females, and tumors in the bones of the feet were much more common than those in the hands. All signs and symptoms were local in distribution. As in other sites, the dominant histologic pattern was categorized as diffuse. With the exception of those patients with lesions in the calcaneus, the prognosis for disease-free survival was excellent. A literature review of cases of ES reported in bones of the hands and feet showed generally comparable results.

Pseudocorpus luteum insufficiency: a local defect of progesterone action on endometrial stroma.

A 23-yr-old woman whose initial complaint was infertility demonstrated glandular stromal dissociation with failure of the endometrial stroma to undergo pseudodecidualization in repeated endometrial biopsies taken late in the luteal phase. As the clinical presentation was consistent with the inadequate corpus luteum syndrome, hormone measurements were performed. The endometrial biopsy was abnormal during cycles in which the serum pattern of progesterone, estradiol, FSH, and LH was normal. Exogenous progesterone did not correct the abnormality. The patient, by in vitro studies, has approximately one half the number of high affinity progesterone-binding sites in the cytosol fraction of her endometrium compared to preparations from two normal control subjects. Since her cytosol-binding protein was qualitatively identical to two control subjects, the incomplete maturation of her endometrial stroma may represent an absence or reduced number of stromal cytosol receptors and/or a resistance to specific hormone action in an individual target tissue.

True papillary carcinoma of the lung: a distinct clinicopathologic entity.

There continues to be confusion as to whether papillary adenocarcinoma (PA) of the lung is a specific histologic entity or simply a variant of bronchioloalveolar carcinoma (BAC). We reviewed our files from 1981 through 1993 for all cases (n = 155) of resected primary lung adenocarcinoma specifically diagnosed as having papillary or bronchioloalveolar features. In addition, a random 10% (n = 67) of all remaining lung adenocarcinomas were reviewed. True PA was diagnosed when > or = 75% of the neoplasm contained papillary structures supported by fibrovascular cores with complicated secondary and tertiary branches. Marked nuclear atypia was present in 100%, and psammoma bodies were seen in 42% of cases. In contrast to BAC, true PA filled and distorted or replaced air spaces in the lung. Thirty-one cases of true PA were found, including 19 men and 12 women (mean age, 64.5 years). The lesions were solitary (n = 27) or multifocal (n = 4) with a mean diameter of 4.1 cm. Forty-five percent of patients had bronchopulmonary lymph node involvement at diagnosis; another 10% had extensive intrapulmonary lymphatic permeation by tumor. Disease-free survival for stage I and II PA was 40% (n = 15) and 25% (n = 8), respectively, at a mean of 3.4 and 3.5 years. Papillary adenocarcinoma of the lung is a distinct clinicopathologic entity with considerably worse morbidity and mortality than BAC.

Interpretation and significance of pathologic findings in transbronchial lung biopsy.

We evaluated the pathologic features and clinical significance of 50 transbronchial lung biopsies from 45 immunosuppressed patients (Group I) and 41 from 39 nonimmunosuppressed patients (Group II). Specific diagnoses were established in only 36% of Group I, and of these two-thirds were infections. Expected inflammatory reactions to infection were absent in most of these immunosuppressed patients. Nonspecific pathologic changes were found in 40%, of which diffuse alveolar damage and interstitial pneumonitis were the most common. The mortality was highest for Group I patients with infections (50%) and with diffuse alveolar damage (56%). In Group II patients specific diagnoses were made in only 7%, although histologic abnormalities were found in an additional 61%. This study emphasizes several important differences which should be considered in evaluating transbronchial lung biopsies from immunosuppressed and nonimmunosuppressed patients. This biopsy procedure is most useful in diagnosing infection in immunosuppressed patients but the histology may be difficult to interpret since the usual inflammatory reactions are often absent. This procedure is also useful in evaluating nonimmunosuppressed patients, although open biopsy may be necessary when clinical and pathologic features do not correlate.

Minute pulmonary meningothelial-like nodules. A clinicopathologic study of so-called minute pulmonary chemodectoma.

The clinicopathologic features of 23 so-called minute pulmonary chemodectomas from nine patients are presented. Eight patients were women and one was a man; age range was 34-75 years (mean, 61). Two specimens were surgical resections and seven were autopsies (incidence, one per 60 autopsies). There was no association with a specific disease process or pathologic condition. Grossly, the lesions were 1-3 mm, tan to yellow, pleural or parenchymal nodules. Six of nine cases had multiple lesions; upper lobes were more often involved. Microscopically, characteristic cell nests expanded alveolar septa. Larger lesions were connected by intervening collagen, often imparting a stellate configuration. Smaller lesions had closely apposed nests with mildly thickened alveolar septa. The nodules were strongly reactive for epithelial membrane antigen (12 of 14) and vimentin (10 of 14), and were uniformly negative for cytokeratin, S-100, neuron-specific enolase, and actin. Ultrastructurally, complex interdigitating cell processes were connected by desmosomes. Occasional cytoplasmic filaments were seen. These nodules lack neuroendocrine features, differ from mesothelium, and strongly resemble meningothelial cells. A more accurate term for these lesions is minute meningothelial-like nodules. Their relationship to larger, solitary pulmonary meningiomas is unclear.

HMB-45 immunohistochemical staining of sentinel lymph nodes: a specific method for enhancing detection of micrometastases in patients with melanoma.

Despite the profound therapeutic and prognostic implications of nodal metastases in patients with melanoma, there is no consensus strategy for the optimal detection of metastases in sentinel lymph node biopsies. Traditional microscopic examination may be too crude to detect scattered, individual tumor cells. Conversely, molecular genetic techniques are prone to false-positive results. The authors evaluated the ability of HMB-45 immunohistochemistry to enhance detection of melanoma cells in histologically negative sentinel lymph nodes. Ninety-six sentinel lymph nodes, collected over a 25-month period from 66 consecutive patients with melanoma, were processed routinely and sectioned serially. Slides 1, 3, and 5 were stained with hematoxylin and eosin. HMB-45 staining was performed on an intervening slide in histologically negative nodes. To assess the background incidence of HMB-45-positive cells in lymph nodes draining the skin, the authors stained 244 cervical and axillary lymph nodes from patients without melanoma. Metastases were apparent microscopically in 12 (18%) of the 66 patients with melanoma. Of the remaining 54 patients, four patients (7%) had lymph nodes harboring individual, scattered HMB-45-positive cells. Benign nevocellular aggregates were present in four of the 96 sentinel lymph nodes (4% nodal incidence), but they were HMB-45-negative. The authors did not observe a single HMB-45-positive cell in the 244 lymph nodes from patients without melanoma. Immunohistochemistry appears to represent a specific means of enhancing tumor detection in sentinel lymph nodes from patients with melanoma.

Placental transmogrification of the lung, a histologic variant of giant bullous emphysema. Clinicopathological study of three further cases.

Placental transmogrification of the lung was described by Chesney in 1978 as an unusual cystic lesion involving a single pulmonary lobe (3). We studied three additional cases with identical clinical and pathologic features. The patients were a 33-year-old woman and men aged 24 and 27 years. Each patient was first seen with respiratory distress; one had repeated pneumothoraces. Radiographically, an enlarging cystic lesion was present in a lower (two) or middle (one) lobe. The lesion had been present for 10 years in one patient. In two patients, mediastinal shift was noted. Lobectomy was curative in all instances. Grossly there was a uni- or paucilocular cyst lined by papillary structures. Microscopically, the papillae contained proliferating blood vessels, lymphoid nodules, smooth muscle, and fat. Sclerotic foci obliterated the vessels in some areas. The growth pattern and topography resembled those of placental villi. Systematic review of the histologic features in other lungs with marked emphysema revealed a spectrum of similar changes and suggested that the lesion in our patients may be a complication of bulla formation and is most likely the clinico-pathologic analog of the "vanishing lung" syndrome (idiopathic giant bullous emphysema).

Pulmonary clear cell carcinoid tumor: another entity in the differential diagnosis of pulmonary clear cell neoplasia.

A clear cell variant of primary pulmonary carcinoid tumor is described. The tumor arose in a 53-year-old woman who was incidentally found to have a solitary pulmonary nodule in the left upper lobe during routine chest roentgenography. Histologically, the tumor was composed of predominantly clear to lightly eosinophilic, polygonal cells with bland nuclei arranged in sheets and nests. Nuclear pleomorphism, necrosis, vascular invasion, and mitotic figures were not seen. The tumor cells were negative for oil-red-O and periodic acid-Schiff stains with and without diastase pretreatment on frozen and formalin-fixed sections, respectively. During immunohistochemical evaluation, the tumor cells were focally positive for cytokeratin and diffusely positive for neuron-specific enolase and chromogranin. Electron microscopy performed on paraffin block-retrieved tissue showed the presence of electron-dense, neurosecretory-type granules and variably sized vacuolated areas within the cytoplasm. the nature of which remained unclear. Intracytoplasmic glycogen or lipid were not identified. To our knowledge, this is the first report of pulmonary clear cell carcinoid tumor.

Salivary gland anlage tumor ("congenital pleomorphic adenoma"). A clinicopathologic, immunohistochemical and ultrastructural study of nine cases.

Salivary gland anlage tumor (SGAT) is a polypoid lesion of the nasopharynx that presents with respiratory distress at birth or within the first few days or weeks of life. Among our nine cases, there was a male predilection (7M:2F). All tumors were in the midline and attached to the posterior pharyngeal wall by a delicate pedicle. The largest tumor measured 3 cm. A biphasic histologic pattern of squamous nests and duct-like structures at the periphery blended into solid, predominantly mesenchymal-appearing nodules centrally. The surrounding submucosal mantle of epithelial structures was consistently immunoreactive for cytokeratin and epithelial membrane antigen, whereas the stromal-like cells of the central nodules showed variable immunopositivity for cytokeratin, vimentin, and muscle-specific actin. Both components were equally reactive for salivary gland amylase. Ultrastructurally, some of the stromal-like cells had features of myoepithelial cells. The histologic and architectural features of SGAT are similar in some respects to the developing salivary gland. It is proposed that the SGAT is a probable hamartoma of minor salivary gland derivation whose origin in the nasopharynx is potentially life-threatening in an infant.

Pulmonary and mediastinal glomus tumors--report of five cases including a pulmonary glomangiosarcoma: a clinicopathologic study with literature review.

Pulmonary and mediastinal glomus tumors are rare lesions, with four previously reported primary pulmonary cases and three mediastinal cases. The authors report one mediastinal glomus tumor, a locally infiltrative type, and four pulmonary glomus tumors, including the first case of primary pulmonary glomangiosarcoma. These tumors show a variety of clinical and pathologic differences from the more common cutaneous variety, including later age at presentation, larger size, and more frequent atypical/malignant features. Mediastinal and pulmonary glomus tumors both have an average patient age at presentation of 45 years. However, compared with their pulmonary counterparts, mediastinal glomus tumors are less common, more often symptomatic, and are larger (average size, 5.4 cm). Additionally, mediastinal glomus tumors more often demonstrate malignant or atypical features. Pulmonary glomus tumors average 3.3 cm in greatest dimension, with the majority measuring less than 2.5 cm. The pulmonary glomangiosarcoma presented was large, measuring 9.5 cm, and showed increased mitotic count (9 mitoses/10 high-power fields), necrosis, cytologic atypia, and was associated with disseminated disease. Regardless of clinical symptoms, histologic features, and even metastases, the vast majority of all benign and malignant glomus tumors are indolent and cured surgically, with adjuvant therapy needed only for occasional patients with more advanced disease. The four patients with glomus tumors reported are currently alive and free of disease as of last follow up. The patient with the glomangiosarcoma developed widespread metastases and died of disease 68 weeks after initial therapy.

Clear cell tumor of the lung. A clinicopathologic, immunohistochemical, and ultrastructural study of eight cases.

We studied eight clear cell tumors of the lung (CCTL) to better define their clinical, immunohistochemical, and ultrastructural features, and to clarify their distinction from other neoplasms, particularly metastatic renal cell carcinoma. Patients ranged in age from 31 to 67 years (mean, 51 years). Seven patients had clinically benign, asymptomatic lesions measuring less than 2 cm in diameter that were devoid of necrosis. The eighth patient had a symptomatic, partially necrotic CCTL 4.5 cm in diameter that metastasized to the liver and peritoneum; the patient died of tumor 17 years after diagnosis. Ultrastructural study of seven CCTL showed interdigitating cell processes (all cases), primitive cell junctions (five of seven cases), intracytoplasmic glycogen (all cases), and rare dense core granules (two of seven cases). Immunohistochemically, paraffin-embedded sections from all eight CCTL were negative for cytokeratin (CK), epithelial membrane antigen (EMA), chromogranin, and vimentin. Focal staining was seen for S-100 protein (three of eight cases), neuron-specific enolase (three cases), synaptophysin (one case), and Leu 7 (one case). Although these findings suggest that at least some CCTL exhibit neuroendocrine differentiation, the tumor's histogenesis remains uncertain. Of more practical importance, the combined absence of CK, EMA, and vimentin in formalin-fixed, paraffin-embedded CCTL virtually precludes confusion with renal cell carcinoma. Although traditionally considered benign, CCTL larger than 2 cm that are symptomatic, and focally necrotic should be regarded as potentially malignant neoplasms.

Cryosurgery of the fetal ductus arteriosus.

The effects of cryosurgical treatment of the fetal ductus arteriosus (DA) on the structure and function of the neonatal DA are assessed for the first time. A cryosurgical probe, cooled with nitrous oxide, was used to freeze the wall of the DA in 5 fetal lambs. Six fetal lambs were used as control animals. After birth, all the cryosurgically treated lambs had a patent DA whereas all the control lambs had a closed DA. Only the cryosurgically treated group had these histologic findings: calcific deposits, necrosis, and focal ganglion cell necrosis in the outer one third to two thirds of the media with a decrease or loss of muscle cells and elastic fibers. This study suggests the feasibility of developing a cryosurgical approach for maintaining patency of the DA.

Neuroblastoma and the differential diagnosis of small-, round-, blue-cell tumors.

Of the solid tumors of childhood, neuroblastoma--the prototypic small-, round-, blue-cell neoplasm--occurs in the youngest patients and has shown the least predictable biologic behavior and response to therapy. It is often confused clinically and histologically with Wilms' tumor, rhabdomyosarcoma, lymphoma, and especially, Ewing's sarcoma. Certain clinical and histologic features that may be useful in prognosis have been identified, however, and a variety of distinctive light microscopic, electron microscopic, and immunohistochemical features may be useful in differentiating this and related tumors. Many of the varied techniques useful in the differential diagnosis of these tumors can now be employed routinely in most laboratories.

The fine structure of so-called minute pulmonary chemodectomas.

Electron microscopy was performed on several minute tumors of the type called chemodectomas, all from the lung of a single patient. The cells had a whorling pattern with extensive interdigitating cytoplasmic processes joined by desmosomes. Except for tangles of cytoplasmic fibrils, the tumor cells had few distinctive organelles. They had no endocrine-like granules and were not associated with nerves or basement membranes. The tumors had little resemblance to paragangliomas, but displayed a puzzling similarity to meningiomas. Our observations permit no definite conclusions as to the histogenesis of these lung tumors. Viewed in the light of recent physiologic studies, they cast doubt on the presence of special chemoreceptive paraganglia in the lung.