213

glass nucleus with finaly dispersed chro- matin. Nucleolated cells, similar to those seen in large cell cancer, are often present but are not ultrastructu- rally different from nonnucleolated tumor cells.

Electron Microscopy in Selection of Pa- tients with Small Cell Carcinoma of the Lung for Medical Versus Surgical Therapy. Iglehart, J.D., Wolfe, W.G., Vernon, W.B. et al. Department of Surgery, Durham Ve- terans Administration Medical Center, Durham, NC 27710, U.S.A.J. Thorac. Car- diovasc. Surg. 90: 351-360, 1985.

Fifty-one cases of small cell carci- noma of the lung were studied by electron microscopy in order to determine if ul- trastructural subsets could be found and if these subsets predicted clinical be- havior. All of these cases were conside- red bona fide small cell carcinoma of the lung by light microscopy. Tumors with ultrastructural features of epithelial differentiation were defined by the pre- sence of well-formed, classic desmosomes joining adjacent cells and by additional features of squamous or glandular diffe- rentiation. Thirty-one tumors (60%) were considered 'typical oat cell' by electron microscopy and 20 (40%) showed features of epithelial differentiation. Fifteen (75%) tumors with epithelial fea- tures were considered operable and nine (45%) were resected with curative intent. In contrast, 26 (84%) tumors considered typical oat cell by electron microscopy presented with extensive metastatic dis- ease. The cancer-free 5-year actuarial survival rate of patients whose tumors showed features of epithelial differentia- tion was 25%. The actuarial survival rate of nine patients who underwent resection of tumors with epithelial features was 38% at 5 years. Only one patient whose tumor was considered typical of oat cell carcinoma by electron microscopy survived 5 years. Our current recommen- dation is to remove all clinically resec- table pulmonary neoplasms with the ex- pectation that these localized small cell tumors are likely to show epithelial fea- tures by electron microscopic analysis.

Neuroendocrine Neoplasms of the Broncho- pulmonary Tract. A Classification of the Spectrt~ of Carcinoid to Small Cell Car- cinoma and Intervening Variants. warren, W.H., Gould, V.E., Faber, L.P. et al. Department of Cardiovascular-Thora- cic Surgery, Rush Medical College, Chica, go, IL 60612, U.S.A.J. Thorac. Cardio- vasc. Surg. 89: 819-825, 1985.

Eighty-one primary pulmonary neuro-

endocrine neoplasms were assessed by the classi- fication of Gould and associates. The neuroendocri- ne features of these tumors were studied by a com- bination of conventional light microscopy, elec- trom microscopy, and immunohistochemical staining for hormonal substances and neuronspecific enolase. In each case, clinical follow-up was obtained to test the prognostic value of this new pathological classification. This study indicated that bron- chial carcinoids are very low-grade neuroendocrine neoplasms that are locally invasive and only oc- casionally metastasize late in their course. Well- differentiated neuroendocrine carcinomas are rela- tively low-grade carcinomas that either present with or subsequently develop nodal or distant metastases in 73% of patients. Intermediate cell neuroendocrine carcinomas are highly aggressive tumors often mistakenly called 'larqe cell undif- ferentiated carcinoma'- Their clinical course is comparable to that of small cell neuroendocrine carcinomas, which has a mean survival of 9 months. The different clinical courses of these tumors demonstrate the predictive value of the proposed classification. It appears particularly valuable to identify well-differentiated neuroendocrine carcinoma as a low-grade carcinoma, distinct from true bronchial carcinoids. This classification may resolve some discrepancies regarding the therapy for and prognosis of 'carcinoids' and their pre- sumed variants.

Large Cell Neuroendocrine T~nors of the Lung. Cli- nical Significance and Histopathologic Definition. Hammond, M.E., Sause, W.T. Pathology Department, LDS Hospital, Salt Lake City, UT 84143, U.S.A. Cancer 56: 1624-1629, 1985.

~¢enty-five cases of neuroendocrine tumors of lung, including bronchial carcinoids (eight), ma- lignant (atypical) carcinoids (nine), and large cell undifferentiated carcinomas (LCAC) with neu- roendocrine differentiation (eight) were analyzed. All carcinoids (BC) could be diagnosed by light microscopy; all patients with these tumors are alive without disease. Five of nine malignant car- cinoids (MC) could be recognized histologically; four of nine were called LCAC and required elec- tron microscopy for diagnosis. Survival correlated best with stage of diagnosis. High-grade neuroendo- crine carcinomas (LCAC-NE) required electron mi- croscopy for their diagnosis. Seven were LCAC hi- stologically; one was diagnosed as malignant car- cinoid (MC). Such tumors resemble small cell ana- plastic carcinomas ultrastructurally and behavio- rally. All eight patients with such high-grade tu- mors died of their disease; three of eight had no nodal metastases at the time of resection. This experience suggests it is clinically important to distinguish neuroendocrine neoplasms since beha- vior is predictable on the basis of morphology.

Large Cell Carcinoma of the Lung. Ultrastructural Differentiation and Clinicopathologic Correlations. Albain, K.S., True, L.D,, Golomb, H.M. et al. Department of Medicine, Loyola University Stritch School of Medicine, Maywood, IL 60153, U.S.A.

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Cancer 56: 1618-1623, 1985.

Light microscopic biopsy specimens from 48 patients were reviewed by two inde- pendent pathologists and classified as large cell carcinoma of the lung by 1981 World Health Organization (WHO) criteria. Sites of primary disease were hilar/medi- astinal in 26 patients, large mid-lung field in 17, and peripheral lung in 5. All material was examined by electron mi- croscopy (EM) for evidence of squamous ('squamous': 15 patients), glandular ('adenocarcinoma': 17 patients), or non- specific ('large cell': 14 patients) ul- trastructural differentiation. Two pa- tients had mixed adenosquamous features. There were 6 patients with Stage I tumors; 5, Stage II; 24, Stage IIIMO; and 13, Stage IIIMI. Of the 14 patients with large cell by EM, ii had unresectable Stage IIIMO or metastatic disease. Only 3 of 27 patients not undergoing resec- tion responded to combined modality the- rapy. There were two long-term survivors free of disease in the resected Stage IIIMO patient category. Overall median survi- val by stage was analyzed, with no sta- tistically significant difference between several of the stage groupings, sugge- sting a worse prognosis for the entire group overall compared to all patients with non-small cell lung cancer. The me- dian survival by EM subgroup was also without significant difference, both overall and within various stage groupings, despite more patients in the large cell category with advanced disease. These data support the unique behavior of patients with large cell carcinoma on light mi- croscopy, but fail to demonstrate that ultrastructural differentiations is of prognostic importance for response or survival.

Clear Cell Carcinoma of the Lung. Edwards, C., Carlile, A. Department of Histopathology, East Birmingham Hospital, Birmingham B9 5ST, U.K.J. Clin. Pathol. 38: 880-885, 1985.

Six tumours of the lung initially clas- sified as clear cell carcinoma, were stu- died. Examination of further material

by light and electron microscopy showed adenocarcinomatous differentiation in three cases and squamous differentiation in two. One case showed the features of a large cell anaplastic carcinoma. The clear appearance of the cytoplasm in pa- raffin sections was due to accumulations of glycogen that were partially removed during processing. It is concluded that clear cell carcinoma is not a single and separate entity.

Pulmona~7 Scar Cancer: A Pathologic Re-

appraisal.

Ignatius-Tak-Min-Kung, Irene-Oi-Lin-Lui, Shee-Loong- Loke, et-al. Department of Pathology, University of Hong Kong, Queen Mary Hospital, Hong Kong; Hong Kong. Am. J. Surg. Pathol. 9: 391-400, 1985.

A total of 49 consecutive specimens of lung cancer were collected prospectively at surgical resection or autopsy from 40 men and nine women, aged 40-74 years. Of the 49 tumors, the gross appearance of 22 fitted the description of a scar cancer, i.e., a tu- mor with pleural puckering and central pigmentation. Nineteen of the 'scar cancers' were peripheral (17 adenocarcinomas and two squamous cell carcinomas); three were central (one squamous cell carcinoma and two adenocarcinomas). In the 19 peripheral 'scar canbers', elastic stains demonstrated the presence of collapsed, unfibrosed lung tissue at the center with traction of the overlying pleura toward it. Elsewhere in the tumor, the elastic framework was either destroyed or expanded by tumor filling the alveolar spaces. None of the 'scar cancers' had a significant desmoplastic reaction that might other- wise explain the scarred appearance. It appeared that local atelectasis was solely responsible for the pleural puckering and central pigmentation. On the other hand, atelectatic lung tissue was not seen in the 27 cancers that did not have the appea- rance of a scar cancer. Tuberculosis was found in I0 of the 49 lung specimens. In only one specimen was the tuberculous lesion anatomically associated with the tumor. There was no evidence of pulmonary infarct in any of the specimens. The term 'scar cancer' was considered inappropriate as there was no preformed fibrous tissue. The scarred appearance was thought to be the result of localized pulmonary atelectasis owing to small airways obstruction by tumor. Association with tuberculosis was considered incidental.

Benign Clear Cell ('Sugar') t~nor of the Lung. A Light Microscopic, Histochemical, and Ultrastructu- ral Study with a Review of the Literature. Andrion, A., Mazzucco, G., Gugliotta, P., Monga, G. Institute of Pathological Anatomy and Histology, University of Turin, Turin, Italy. Cancer 56: 2657- 2663, 1985.

A case of a benign clear cell 'sugar' tumor of the lung is reported. Light microscopy showed a uniform proliferation of clear cells filled with abundant glycogen. At the ultrastructural level, tumor cells were rich in free monogranular and ro- sette-forming glycogen, but no membrane-bound gly- cogen was demonstrated. Some cells showed plasma membrane interdigitations, microvilli, and macula occludens-type junctions. Many polymorphic secre- tory and sporadic haloed neurosecretory-like granu- les were observed, but argyrophil strains as well as a large set of immunohistochemical reactions specific for APUD derivation had negative results. A literature review of this puzzling entity with particular emphasis on the histogenetic hypotheses is presented, and a derivation from epithelial non- ciliated bronchiolar (Clara)cells or epithelial se- rous cells is suggested.