The origin of platelets (Pt) from megakaryocytes (MK) is beyond question, but the mechanism whereby Pts are released from the precursor cell is still debated . A widely-held theory claims that the MK plasma membrane invaginates to form demarcation membranes (DMS), which delineate Pt territories . Accordingly, Pts would be derived mostly from the periphery of the MK, and the MK and Pt plasma membranes would have to be virtually identical . Since, on morphologic grounds, this theory is untenable, several aspects of thrombocytopoiesis were reexamined with the help of membrane tracer and freeze-fracture analyses of freshly-collected human and cultured mouse MK . To our surprise, freeze-cleavage of the MK plasma membrane revealed that the vast majority of intramembranous particles (IMP) remained associated with the protoplasmic leaflet (P face), whereas the partition coefficient of IMPs of the platelet membrane was the reverse . This is the first time that any difference between MK and Pt membranes has been determined. Replicas of freeze-fractured MK that were in the process of thrombocytopoiesis revealed an additional novel phenomenon, i .e., numerous areas of membrane discontinuity that appeared to be related to Pt discharge . When such areas were small, the IMP were lined up along the margin of the crevice . At a later phase, a labyrinth of fenestrations was observed . Thin sections of MK at various stages of differentiation showed that Pt territories were fully demarcated before connections of the DMS with the surface could be found . Therefore, the Pt envelope is probably not derived from invaginations of the MK plasma membrane . When living, MK were incubated with cationic ferritin or peroxidase at 37°C, the tracers entered into the DMS but did not delineate all membranes with which the DMS was in continuity, suggesting the existence of distinctive membrane domains . Interiorization of tracer was not energy-dependent, but arrested at low temperatures . At 4°C the DMS remained empty, unless there was evidence that Pts had been released . In such instances, the tracers outlined infoldings of peripheral cytoplasm that was devoid of organelles . Thus, the majority of Pts seem to originate from the interior of the MK, and the surface membranes of the two cells differ in origin and structure . The observations do not only throw new light on the process of thrombocytopoiesis, but also strengthen the possibility that MKs and Pts may be subject to different stimuli .Ever since the recognition by Heidenhain in 1894 (1) that the cytoplasm of megakaryocytes (MK)' is organized into distinc-'Abbreviations used in this paper: DMS, demarcation membrane ; IMP, intramembranous particles ; MK, megakaryocytes; Pt, platelets, P-and E-face, protoplasmic and ectoplasmic faces . tive territories, the discovery by Wright in 1906 (2) that megakaryocytes give rise to circulating platelets, and the electron microscopic description of the demarcation membrane system (DMS) by Yamada in 1957 (3), the mechanism whereby platelets are ...

A 55-year-old man had adenoid cystic carcinoma of the esophagus metastatic to the lungs and right supraclavicular fossa. He was treated with local radiation therapy to the esophagus and supraclavicular fossa, followed by combination chemotherapy with doxorubicin, mitomycin C, and 5-fluorouracil (5-FU). After a modest initial response, disease progression was noted in the pulmonary nodules. He was then treated with cisplatin, cyclophosphamide, vincristine, and doxorubicin. After two cycles of this regimen, there was complete regression of his pulmonary nodules, which was sustained for 5 months. A review of 44 literature cases of esophageal adenoid cystic carcinoma contrasted with adenoid cystic carcinoma of salivary gland origin indicated that the esophageal adenoid cystic carcinomas have a high tendency to metastasize (76% of cases) and a much poorer prognosis, with only 23% 1-year survival rate. It was concluded that esophageal adenoid carcinoma is clinopathologically distinct from the salivary gland variant, and that combination chemotherapy may be an effective treatment modality for this cancer.

A 20-year-old woman had a sporadic case of medullary thyroid carcinoma (MTC) metastatic to the lungs. After a transient response to streptozotocin and doxorubicin, new subcutaneous lesions appeared on the left chest wall and there was progression of pulmonary disease. Because MTC is one of the amine precursor uptake and decarboxylation (APUD) tumors, treatment was undertaken with agents active in these diseases. Dacarbazine and 5-fluorouracil, given daily for 5 days every 4 weeks, resulted in complete resolution of pulmonary and subcutaneous lesions and a sharp decrease in tumor marker levels that lasted 10 months. Recurrence of the pulmonary disease lead to her death 21 months after presentation. Thus, the chemo-responsiveness of MTC may be akin to that of other APUD carcinomas (APUDomas) and treatment of metastatic MTC and other APUDomas with the combination of dacarbazine and 5-fluorouracil appears to merit further study.