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have resulted from a delay in conduction from cell to cell in the ordinary ventricular myocardium, as in hyperkalemia. Yet, the possibility of this being due to a selective action on the Purkinje fibers or in the Purkinjemyocardial junction cannot be excluded. Considering this observation and the available reports in the literature dealing with toxicity of imipramine and its sister compound, desipramine should be used with caution in patients with limited coronary reserve. Although significant rhythm abnormalities were not observed in our case, patients with desipramine overdosage should be monitored in intensive coronary care units since arrhythmias are common cardiac complications.T,s These arrhythmias may prove resistant to conventional therapy8 and it is therefore very important to prevent their occurrence. Since no antidote is available, attention should be concentrated on supportive measures as suggested in the literature for the treatment of imipramine overdosage: 3 •4 •11 •14 I. Attempts at removing whatever drug is still in the stomach with lavage. 2. Adequate hydration with central venous pressure monitoring and caution to avoid heart failure. 3. Promoting osmotic diuresis with mannitol. 4. Good oxygenation, hoping to limit the possible subendocardial injury. 5. Isoproterenol may be used in some cases for its inotropic and chronotropic effects, and digitalis is advisable if failure supervenes. REFERENCES

1 DiMascio A, Henninger G, Klerman GL: Psychopharmacology of imipramine and desipramine: A comparative study of their effects in normal males. Psychopharmacolo.gia 5:361-371, 1964 2 Hollister LE: Evaluation of desipramine in depressive states. J New Drugs 3:161-166, 1963 3 Harthorn JW, Marcus AM, Kaye M: Management of massive imipramine overdosage with mannitol and artificial dialysis. New Eng J Med 268:33-36, 1963 4 Prout BJ, Young J, Goddard P: Imipramine poisoning in childhood and suggested treatment. Brit Med J 1:972, 1965 5 Rao AV: Imipramine-induced auricular fibrillation. J Indian M A47:36, 1966 6 Sloman L: Myocardial infarction during imipramine treatment of depression. Canad Med Assoc J 82:20-22, 1960 7 Bucher HW, Stucki P: Cardiac complications in desipramine intoxication. Schweiz Med Wschr 97:519--521, 1967 8 Colvard C: Overdosage of desipramine hydrochloride with marked EKG abnormalities. Southern Med J 61: 1218, 1968 9 Gillette JR, Dingell JV, Sulser F, et al: Isolation from rat brain of metabolic product desmethylimipramine, that mediates the antidepressant activity of imipramine. Experientia 17:417-418, 1961 10 Cairncross KS, Gershon S: A pharmacological basis for the cardiovascular complications of imipramine intoxication. Med J Aust 49:373-375, 1962 11 Sueblinvong V, Wilson JF: Myocardial damage due to imipramine intoxication. J Pediat 74:475-478, 1969 12 Sigg EB, Osborne M, Koed B: Cardiovascular effects of

imipramine. J Pharmacal Exp Ther 141:237-243, 1963 13 Motin J, Evreux JC, Vedrinne J: Toxicite' cardiovasculaire de l'imipramine. Rev Lyon Med 16:309-310, 1967 14 Sacks MH, Bonforte RJ, Lasser RP, et al: Cardiovascular complications of imipramine intoxication. JAMA 205:588590, 1968 Reprint requests: Dr. Chahine, Peter Bent Brigham Hospital, Boston 02115

Primary Tumors of the Diaphragm* Gretar 0/afsson, M.D., •• Alf Rausing, M.D.,t and Otto Holen, M.D.t

During the last 100 years (1868-1968) only 84 cases of primary tumor of the diaphragm have been reported, the ratio of benign to mallgnant tumon being 5%:33. The most frequently occurring benign tumon were cystic formations. Among the malignant tumon, different types of sarcoma dominated and fibrosarcoma was the most common. rimary tumors of the diaphragm are pathologic P changes which are rare, as well as difficult to diagnose. The symptoms vary and do not follow a uniform clinical pattern. Routine x-ray examinations of the chest do not give a characteristic picture either. When confronted with an x-ray shadow in this area, the possibility of diaphragmatic tumors should always be borne in mind in spite of their rare occurrence. In 1868, Granchert reported the first case of primary diaphragmatic tumor. The tumor was discovered at autopsy and was diagnosed as a fibroma. In later publications only one or some few cases have been reported. Wiener and Chou2 in 1965 reported a case of tumor of the diaphragm and at the same time presented a critical review of the world literature on the subject from 1868 to 1963. It appeared from this report that 71 cases had been recorded and of these 43 were benign and 28 malignant tumors (Table 1}. The purpose of this article is to deepen the review of the literature up to and including 1968 and to report a case treated in our clinic. CAsE REPORT

A 16-year-old boy was admitted to the Department of Thoracic Surgery, Malmo General Hospital, Malmo, Sweden, on March 14, 1968. On admission, he complained of breathing difficulties and severe pains in the left hemithorax, as well as aching in the epig~trium. He related that while playing at school seven days earlier, he had received a karate-like blow across the epigastrium, which was not especially severe. Chest x-ray examination showed total density in the left chest with shifting of the mediastinum to the right ( Fig 1 ) . °From the Departments of Thoracic Surgery and Patholo!Q:. Malmo Allmiinna Sjukhus, University of Lund, Malmo, Sweden. •• Assistant Professor of Thoracic Surgery. Presently at Landspitalinn, Reykiavik Icleand. tTeacher of Pathology. . tAssistant Professor of Thoracic Surgery.

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PRIMARY TUMORS OF DIAPHRAGM Table !-Primary tumor of the diaphraiJm

Patho-anatomic diagnosis

Cases collected by Wiener & Chou Cases collected by 1868-1963 the authors 1963-1968 Total

Benign Angiofibroma Adenoma, adrenal cortical Adenoma liver cell Chondroma Cyst, bronchial, mesothelial, teratoid

3

12

I (Nilant'ev) 0 0 0 6 (Kozlov 2, Juvara I, Gol'dfarb I,

Ovnatanian I, Dobek I) Fibroma Fibrolymphangioma Fibromyoma Hamartoma Lymphangioma, cystic Leiomyoma Lipoma Mesothelioma Neurilemmoma Neurofibroma Rbabdomyofibroma

3

4

18 4

I

I (Santy) 0 0 I (Zagoraki) 0 0

9

0

9

I 2

0 0

I 2

4

0 0

4

2 I

Malignant Fibroangioendothelioma Fibromyosarcoma Fibrosarcoma Hemangioendothelioma Hemangiopericytoma Leiomyosarcoma Myosarcoma, undifferentiated myoblastic sarcoma Neurofibroaarcoma Rhabdomyosarcoma Sarcoma Sarcoma, endothel., vascular Sarcoma, mi1ed cell, polymorphocellular Sarcoma, undifferentiated Synovioma, malignant Mesenchymoma

I 2

8

0

I

0 I (Merlier) I (Kozlov)

2 9 2

0 0

2

0

2

2 2 2

0 0 I (Ovnatanian)

2 2 3

2

0

2

2

0

2 2

I

I (Authors) 0 I (Juvara)

0

71

14

FIGURE l. Chest x-ray film showing total density in the left chest with shifting of the mediastinum to the right. Most of the nuclei had a deficiency in chromatin. The tumor showed numerous mitoses. The stroma was sparse with few thin-walled vessels. Some small necrotic areas with hemorrhage were seen. Silver staining showed very sparse reticulin threads and van Gieson's staining revealed almost no collagen between the isolated cells. Myofibrils could not be verified and the cell picture was not characteristic of leiomyosarcoma. No transverse striation was seen. In some smaller parts the structure was spongy with elongated cells arranged in a plexiform network resembling primitive mesenchyma. No histiocytic cell forms or giant cells were found. On special staining, no hemosiderin or fat was seen. The diagnosis established was: undifferentiated sarcoma of the diaphragm (Fig 2). The patient received postoperative cobalt treatment totaling 1800 rad. He was discharged from the hospital in good general condition on the 24th day; chest x-ray film appeared normal. Ten days later he was admitted again, complaining of breathing difficulties and pains in the left chest. Chest x-ray examination showed density in the left chest and partial collapse of the left lung (Fig 3). A pleural drain was inserted

85

No breath sounds were heard over the whole left hemithorax. Blood pressure was 130/70 mm Hg. Blood hemoglobin was 11.0 grams per 100 ml; other routine laboratory tests were also normal. Intrathoracic bleeding was confirmed, and the patient was operated upon. The bleeding originated from a tumor, almost as large a.~ a golf ball sih1ated in the left diaphragm dorsal to the phrenic nerve and 2 em from the pericardium. The htmor was extirpated, and the excision was done in normal diaphragm and appeared to have been radical. Pathologic Report

Microscopic examination revealed a tumor consisting of numerous elongated or rounded cells growing in poorly outlined streaks or spirals or in undifferentiated cell nests.

CHEST, VOL. 59, NO. 5, MAY 1971

FIGURE 2. Histologic appearance of the tumor (hematoxylineosin x 184).

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FtcURE 3. Chest x-ray film on readmission (two weeks after the patient was discharged from hospital) again showing marked density in the left chest and partial collapse of the left lung. and blood-mixed exudate was withdrawn. The bleeding continued and rethoracotomy was therefore performed. At operation, numerous exuberant metastatic tumor lesions were seen on the visceral and parietal pleural surfaces, with copious and diffuse bleeding. Radical operation could not be performed, but to abate the hemorrhage, thoracoplasty, as well as ligation of the intercostal arteries 1-V were performed. Biopsy done at this operation showed the same microscopic picture as that seen in Figure 2. After this operation the patient was given x-ray treatment of the entire left chest to a total of 4550 rad. The patient expired in his home four months later. Autopsy was not performed. DISCUSSION

When Wiener and Chou2 reported a case of primary fibroma of the diaphragm, at the same time they presented a critical review of the literature from the very first case that had been reported in 1868 up to 1963 (Table 1). They eliminated those cases where it was not certain that the tumor lesions were primary, as well as those cases in which no pathologicoanatomic diagnosis had been established. We applied the same criteria for collecting 13 cases reported in the literature from June, · 1963 (Table 1) .a-n Most of the patients were in the age group 40-50 years, but all ages were represented. The youngest patient was a 26-day-old girl with hemangioendothelioma12 and the oldest an 80-year-old woman with mesothelioma.13 The ratio of men to women is approximately the same (1 :1.1) . This also applies to the right and left diaphragm with the left side slightly dominating. The diagnosis can be difficult to establish because in the first place these tumors are very rare and secondly because the symptoms vary and do not follow a uniform

pattern. The following symptoms are the most common (in order of frequency) : pains in the epigastrium or in the lower part of the chest, cough, dyspnea and gastrointestinal discomfort. Twenty percent of the cases are asymptomatic and in 75 percent of these, the tumor is detected at routine chest x-ray examination. Ordinary x-ray examinations of the chest do not always give a characteristic picture, but the use of diagnostic pneumoperitoneum or pneumothorax, as well as bronchoscopy, may be of value, though in many cases not conclusive. The ratio of benign to malignant tumors is 52 :33 (61 percent to 39 percent) . The most frequently occurring benign tumors are cystic formations such as bronchial, mesothelial and teratoid cysts. They constitute 35 percent of the benign cases. The majority of malignant tumors consist of sarcomas among which fibrosarcoma dominates constituting 27 percent of the malignant cases. Our case may have certain similarities with fibrosarcoma in some small parts where the cells grow in welloutlined streaks. However, the almost total absence of collagenous and reticulous fibrils prevents verification of such a differentiation and likewise no positive signs of development from smooth musculature or other vascular component are present. The partially diHuse mode of growth argues against a neurogenic origin and the monomorphic cell picture, as well as the absence of hemosiderin and fat in the tumor makes a histiocytic genesis less likely. We must therefore hold to the diagnosis undifferentiated sarcoma, as neither cell picture nor stroma indicates specific differentiation.

REFERENCES 1 Grancher M: Tumeur vegetente du centre phrenique du diaphragme. Bull Soc Anat Paris 43:385, 1868 2 Wiener MF, Chou WH : Primary tumors of the diaphragm. Arch Surg 90:143, 1965 3 Nifant'ev OE: A case of a primary tumor of the diaphragm. Grudn Khir 7 :115, 1965 4 Kozlov VP: Neoplasms and cysts of the diaphragm. Vestn KhirGrekov93:108, 1964 5 Juvara I, Priscu A: Primary congenital diaphragmatic tumors. Surgery 60:255, 1966 6 Gol'dfarb MG: Dermoid cysts of the diaphragm. Vestn Roentgenol Radiol39:61, 1964 7 Ovnatanian KT, Zavgorodnii LG, Karvets VM: Diaphragmatic cysts and neoplasms. Crudn Khir 6:76, 1964 8 Dobek J, Majewski C, Moll J : Acase of teratomatous cyst of the diaphragm. Przegl Lek 23:797, 1967 9 Santy P, Galy P, Chassard A: Les tumeurs conjonctives primitives du diaphragm. J Franc Med Chir Thorac 18:745, 1964 10 Zagorski W: A case of a neoplasm of the diaphragm. Pol Tyg Lek 22:1426, 1967 11 Merlier M, Guerin R, Vayre P: Sarcome fibro-blastique du diaphragme inextirpable. Telecobaltherapie. Bon resultat apres 4 ans. Confront Radioanatoinoclin 7 :93, 1967 (suppl Presse Med 75 (No 8 ), p 24 1967) 12 Van Alstyne WK: Hemangioendothelioma of diaphragm. Amer J Roentgenol53 :373, 1945 13 Rosenthal M, Fissel BP: Mesothelioma of diaphragm. Arizona Med 2:231 , 1945 Reprint requests: Dr. Olafsson, Landspitalinn, Reykjavik, Iceland

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