GYNECOLOGIC

ONCOLOGY

41, 250-254 (1991)

CASE REPORT Diffuse Pulmonary Carcinomatous Embolization: A Rare and Fatal Manifestation of Ovarian Cancer LOUIS R. B&IN,

AND STAVROS RAPTIS, M.D.

M.D.,’

Departments of Pathology and Surgery, McGill University, and the Sir Mortimer B. Davis Jewish General Hospital, Montreal, Quebec H3T 1 E2, Canada Received

October

A 44-year-old female presentedwith dyspnea and lethal respiratory failure secondaryto pulmonary emboliccarcinomatosis asa manifestationof ovarian serouscystadenocarcinoma.Diffuse involvement of pulmonary arteriolesand musculararteriesranging from 30 to 950 pm in diameter wasobservedin conjunction with slight dilatation of pulmonary arteries.Vascularintraluminal changesincluded the presenceof free clustersof malignant cells, superimposedthrombosis, varying degreesof eccentric fibromyxoid intimal proliferation with entrappedmalignantcells, and luminal obliteration with neovascularization.The pathobiological aspectsof this unique manifestation of ovarian neoplasiaare discussed. Q1991 hdemic PRS, IIIC.

INTRODUCTION Intra-abdominal

involvement

of the peritoneum and

omentum is the most prominent pattern of metastatic dissemination in ovarian carcinoma [ 1,2]. Extra-abdominal spread usually occurs in a setting of well-documented disease and most commonly involves the lung and pleura as solid tumor deposits [1,3]. We report a patient with FIG0 stage IV serous cystadenocarcinoma of the ovaries who presented with rapidly progressive respiratory failure and subacute car pulmonale secondary to diffuse pulmonary embolic carcinomatosis (PEC).

at: Department of Montreal, Quebec

250 $1.50

Copyright 0 1991 by Academic Press, Inc. All rights of reproduction in any form reserved.

FINDINGS

The right and left ovaries measured 25 x 20 x 15 and 9 x 9 x 5 cm, respectively, and weighed 1300 and 380 g, respectively. Both ovaries were multilobulated, and the cut surfaces showed grey-white solid areas with foci of necrosis and hemorrhage and cysts containing either straw-colored clear or hemorrhagic fluid. The tumor, characterized histologically by a predominant tubulopapillary or solid pattern, was composed of cuboidal cells with amphophilic cytoplasm, vesicular nuclei, and ma-

A 44-year-old white female, gravida 2, para 2, presented with a 3-day history of severe and progressive dyspnea. For the last 4 years, she had been treated for

OU90-8258/91

bipolar affective disorder without any other documented disease. Upon further inquiry, symptoms of weakness, anorexia, lethargy, and increasing abdominal girth of about l-year duration were elicited. Examination revealed an ill-appearing noncyanotic patient with a blood pressure of 90/70 mm Hg, a heart rate of llS/min, and a respiratory rate of 32/min. A hard and nonmobile mass was palpated in the lower abdomen. No evidence of pleural effusion or ascites was noted. No fluid was obtained for cytologic examination. Blood gases revealed a pH of 7.35, a PaO, of 45 mm Hg, and a PaCO, of 20 mm Hg. The electrocardiogram indicated a right-sided heart strain but no right ventricular hypertrophy. Chest X rays revealed a diffuse plate-like atelectasis. A ventilation-perfusion scan revealed multiple small- and intermediate-size peripheral perfusion defects. On the basis of the presumptive diagnosis of massive pulmonary embolism, anticoagulation with heparin was started. An attempted insertion of a filter in the inferior vena cava was unsuccessful. The patient died from respiratory arrest 12 hr after admission, and a complete autopsy was performed. PATHOLOGIC

CASE REPORT

’ To whom correspondence should be addressed Pathology, 375.5 Chemin de la Cote-St. Catherine, H3T lE2, Canada.

31, 1990

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CASE REPORT

FIG. 1. (Ovarian serous cystadenocarcinoma depicting a tubulopapillary and eosin, x 100).

architecture with cellular stratification and cytologic atypia (hematoxylin

cronucleoli (Fig. 1). There were scattered pleomorphic or multinucleated cells. Significant mototic activity was present. There were 1300-ml ascites and multiple peritoneal tumor implants. There were metastases in periaortic and bronchopulmonary lymph nodes. The pleural cavities contained 500 ml of clear straw fluid. Visceral and parietal pleura had a smooth and glistening surface. The right and left lungs weighed 660 and 450 g, respectively. Slight dilatation of the pulmonary arteries and main branches was noted. A single 0.4 x 0.3-cm tumor nodule was seen in the right upper lobe. Histologic examination revealed diffuse and extensive intravascular tumoral embolization with involvement of vessels ranging from 30 to 950 pm diameter but mostly less than 450 pm. Intraluminal clusters of neoplastic cells were found either free (Fig. 2) or, more frequently, adherent to organized fibrinohemorrhagic/thrombotic material (Fig. 3). More advanced lesions were characterized by fibromyxoid intimal proliferation with entrapped tumor cells, focal attenuation of the media, and varying degrees of eccentric luminal narrowing. Occluded vessels by fibromyxoid tissue had superimposed neovascularization (Fig. 4). Plexiform lesions were not seen. Only one microscopic focus consistent with peribronchial lymphatic involvement was seen. Interestingly, the grossly apparent small tumor nodule which was composed of neoplastic cells with fibrosis was closely related to a 300~pm muscular artery containing a tumor embolus, suggesting that this

nodule was a parenchymal extension of the tumor thrombus. The right heart was moderately dilated with minimal hypertrophy. DISCUSSION Pulmonary tumor embolization is a well-documented phenomenon in carcinoma of the breast, stomach, colon, pancreas, liver, kidney, prostate, thyroid, or even parotid gland [4-81. While this phenomenon is usually recognized at autopsy, it may occasionally be the manifestation of an occult primary [4,5,9,10]. In a large autopsy series, including thorough examination of the lungs, pulmonary vascular tumor emboli were observed in 26% of patients who died having a variety of carcinomas [4]. Tumor embolization was a significant factor contributing to the demise in 8% of all these patients, whereas it was considered the cause of death in about 3% [4]. In our view, the term pulmonary embolic carcinomatosis is most legitimate for the latter group of patients sustaining significant morbidity and rapid deterioration. In gynecologic neoplasia, PEC has been documented with gestational trophoblastic disease [4,11]. Although the occurrence of tumor emboli in pulmonary capillaries has been seen in ovarian carcinoma [2], its fulminant manifestation as lethal PEC appears exceptional. Dyspnea and car pulmonale are the overwhelming but nonspecific manifestations of PEC and can occur in small-

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BBGIN AND RAPTIS

FIG. 2. Pulmonary embolic carcinomatosis. Intravascular, free-floating clusters of malignant cells are present (hematoxylin and eosin,

vessel thromboembolic disease or primary pulmonary hyperter Ision [5,12,13]. However, the symptomatology of PEC iIS usually of brief duration and more rapidly progressil yre, with an average survival of about 3 weeks after

X

loo).

the appearance of sympboms [12]. Because of its r apid evolution, PEC is unlikely to reveal the radiographi ic pulmonary changes found in long-standing pulmonat ‘Y hYpertension [11,12,14-161. Pulmonary angiography is;aIften

FIG. 3. Pulmonary embolic carcinomatosis. Eccentric luminal involvement by organizing thrombotic material with entrapped maligna .nt cells is seen (hematoxylin and eosin, x 100).

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CASE REPORT

FIG. 4. Pulmonarv emobilic carcinomatosis. Intraluminal malignant cells are seen (hematoxylin and eosin, X 100).

vascular fibromyxoid

negative [12] and is considered a high-risk procedure in this clinical setting [9,16,17]. The ventilation-perfusion scan may reveal multiple peripheral defects, leading to the misdiagnosis of pulmonary thromboembolism, as exemplified in our own case. The diagnosis of PEC is made pathologically since the presence of intraluminal neoplastic cells is diagnostic. When prominent intravascular organizing thrombotic-like changes are present, a diligent search for neoplastic cells is required in all cases, even in the absence of clinically documented neoplasia. Indeed malignant cells may be sparse and of discontinuous intraluminal distribution on biopsy material [5]. The histologic changes encountered in PEC differ significantly from those of plexiform arteriopathy, a condition ascribed to primary pulmonary hypertension or congenital heart disease. Predominant eccentric or concentric mural thickening, mostly due to organizing thrombotic material and/or fibromyxoid intimal thickening with entrapment of neoplastic cells, and progressive attenuation of the media are diagnostic features of PEC [5,6,10,12]. In addition, many vascular channels can be occluded by fibromyxoid tissue with superimposed intraluminal neovascularization, as illustrated in our case (Fig. 4) [5]. This spectrum of changes has been referred to as carcinomatous arteriopathy [5,12]. In contrast, plexiform arteriopathy shows concentric medial/intimal hypertrophy with significant cellularity, extraarterial neovascularization, fibrinoid vascular necrosis, and plexiform

obliteration

and neovascularization

with a few entr ,apped

lesions [5,13]. The pathophysiologic mechanism of hypoxemia and pulmonary dynamics in PEC are unknown since most patients are too ill to be studied [12]. Mechanisms such as abnormalities of ventilation, perfusion, or diffusion have been suggested to explain the hypoxemia [14]. However, occlusion of massive portions of the pulmonary microvasculature is responsible for the increased pulmonary resistance, which will lead to subacute car pulmonale [6,12]. Because of the brief duration of increased vascular resistance, the right cardiac hypertrophy may not be significant [14]. Interestingly, no good correlation has been established between pulmonary physiologic alterations and morphologic changes in the pulmonary vasculature [5]. PEC is much less frequently encountered than pulmonary lymphangitic carcinomatosis, a condition also characterized by rapidly progressive respiratory failure [5,18]. The latter is a distinct clinicopathologic entity showing distinctive radiographic patterns [19] and pulmonary function tests indicative of a restrictive syndrome [5]. Morphologic distinction from PEC is based on the observations that lymphatics lack an elastic lamina and that intralymphatic tumor cells are usually associated with neither an organizing process nor intimal fibromyxoid proliferation [20]. Concomitant tumor involvement of a few lymphatics in our case is not surprising and has been previously documented in conjunction with PEC [5,14,16].

254

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AND RAPTIS

PEC can occur as a rare and fulminant manifestation of stage IV gynecologic neoplasia. The diagnosis is established on biopsy material, since the symptomatology is nonspecific. Cytologic examination of blood removed during catherization of the pulmonary artery, although of limited sensitivity, may offer a new method for confirming the presence of circulating neoplastic cells in this clinicopathologic setting [21]. It is undetermined whether early pathologic confirmation of this entity and aggressive chemotherapeutic treatment would alter the dismal prognosis. REFERENCES 1. Abrams, H. L., Spiro, R., and Goldstein, N. Metastases in carcinema. Analysis of 1000 autopsied cases, Cuncer 3, 74-85 (1950). 2. Bergman, F. Carcinoma of the ovary. A clinicopathological study of 86 autopsied cases with special reference to mode of spread, Acta. Obstet. Gynecol. &and. 45, 211-231 (1966). 3. Kerr, V. E., and Cadman, E. Pulmonary metastases in ovarian cancer. Analysis of 357 patients, Cancer 56, 1209-1213 (1985). 4. Winterbauer, R. H., Elfenbein, B. I., and Ball, W. C. J. R. Incidence and clinical significance of tumor embolization to the lungs, Am. J. Med. 45, 271-290 (1968). 5. Mark, E. J. Lung biopsy interpretation, Williams & Wilkins, Baltimore (1984). 6. Kane, R. D., Hawkins, H. K., Miller, J. A., and Note, P. S. Microscopic pulmonary tumor emboli associated with dyspnea, Cancer 36, 1476-1482 (1975). Willett, I. R., Sutherland, R. C., O’Rourke, M. F., and Dudley, F. J. Pulmonary hypertension complicating hepatocellular carcinoma, Gastroenterology 87, 1180-1184 (1984). Gonzalez-Vitale, J., and Garcia-Bunuel, R. Pulmonary tumor emboli and car pulmonale in primary carcinoma of the lung, Cancer 38, 2105-2110 (1976). Brisbane, J. U., Howell, D. A., and Bonkowsky, H. L. Pulmonary hypertension as a presentation of hepatocarcinoma. Report of a

case and brief review of the literature, Am. J. Med. 68, 466-469 (1980). Scully, R. E., Galdabini, J. J., and McNeely, B. U. Case records lo. of the Massachusetts General Hospital, N. Engl. J. Med. 303,10491056 (1980). 11. Hendrickse, J. P. de V., Willis, A. J. P., and Evans, K. T. Acute dyspnea with trophoblastic turnours, J. Obstet. Gynaecol. Br. Emp. 72, 376-383 (1965). 12. Scully, R. E., Mark, E. J. McNeely, W. F., and McNeely, B. U. Case records of the Massachusetts General Hospital, N. Engl. J. Med. 317, 225-235 (1987). 13 Katzenstein, A.-L. A., and Askin, F. B. In Surgical pathology of non-neoplastic lung disease (J. L. Bennington, Ed.), Saunders, Philadelphia (1982). 14. Altemus, R. L., and Lee, R. E. Carcinomatosis of the lung with pulmonary hypertension. Pathoradiologic spectrum, Arch. Intern. Med. 119, 32-38 (1967). 15 ’ Durham, R. J., Ashley, P. F., and Dorencamp, D. Cor pulmonale due to tumor emboli. A review of literature and report of a case, J. Am. Med. Assoc. 175, 757-760 (1961). 16. Chakeres, D. W., and Spiegel, P. K. Fatal pulmonary hypertension secondary to intravascular metastatic tumor emboli, Am. J. Roentgenol. 139, 997-1004 (1982). 17. Mills, S. R., Jackson, D. C., Older, R. A., Heaston, D. K., and Moore, A. The incidence, etiologies and avoidance of complications of pulmonary angiography in a large series, Radiology 136, 295300 (1980). 18. Kennedy, K. E., Christopherson, W. A., and Buchsbaum, H. J. Pulmonary lymphangitic carcinomatosis secondary to cervical carcinoma: A case report, Gynecol. Oncol. 32, 253-265 (1989). l9 Yang, S-P., and Lin, C-C. Lymphagitic carcinomatosis of the lungs. ’ The clinical significance of its roentgenologic classification, Chest , 179-187 (1972). 62, 20. Hammar, S. P. Common neoplasms, in Pulmonary pathology (D. H. Dail and S. P. Hammer, Eds.), Springer-Verlag, New York, pp. 727-845 (1988). 21. Masson, R. G., and Ruggieri, J. Pulmonary microvascular cytology. A new diagnostic application of the pulmonary artery catheter, Chest 88, 908-914 (1985). 22. Bagshawe, K. D., and Brooks, W. D. W. Subacute pulmonary hypertension due to chorionepithelioma, Lancet 1,653-658 (1959).

Diffuse pulmonary carcinomatous embolization: a rare and fatal manifestation of ovarian cancer.

A 44-year-old female presented with dyspnea and lethal respiratory failure secondary to pulmonary embolic carcinomatosis as a manifestation of ovarian...
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