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Home , Epithelium, Mesothelium

MESOTHELIAL TURIORS

CHARLES F. GESCHTCKTER, M.D. (From the Siirgicd Piithologictil LaDorat ory, Deportmelit of Surjityv, Johns fZopkins Elo~pitaland Univerhity)

The of the embryo separates early into two major divisions. A paraxial or somatic portion forms the sclerotome. A coelomic or visceral por- tion forms the splanchnocoele and the for the genito-urinary organs. Both the somatic and the visceral mesoderm give rise to epithelial and mesen- chymal elements. In the somatic mesoderm the primitive myo- is replaced by voluntary muscle; the forms the various types of con- nective tissue, including cartilage, bone, fibrous tissue, and fat. In the coelomic or visceral mesoderm the epithelial derivatives include the meso- thelium in the serous cavities and the epithelium of the genito-urinary organs; the mesenchymal elements form smooth muscle and angioblastic tissue from which are derived the vessels, lymphoid and myeloid elements. The major divisions and derivatives of the mesoderm are indicated in the outline below:

SOMATICMESODERM Myo-epithelium ...... Voluntary muscle Mesenchyme ...... Connective tissues (cartilage, bone, etc.) VISCERALMESODERM Mesenchyme ...... Angioblastic tissue, smooth muscle Coelomic epithelium ...... , genito-urinary epithelium

The splanchnocoele, the major derivative of the coelomic cavity, gives rise to the special serous cavities of the body, including the peritoneal, pericardial and pleural cavities, which are lined by persisting coelomic epithelium-the mesothelium. Persisting portions of mesodermal partitions which once di- vided the coelomic chamber form the . A tendency for the coelomic epithelium to persist as such and for the underlying mesoderm to form vascu- lar rather than muscle is characteristic of the derivatives of the splanchnocoele. The tumors derived from the pleura, , and , to which the name is given, show similar tendencies. Their components are epithelial and fibrous in nature. The more malignant tumors are extremely vascular (Fig. 1). In the head region of the embryo, the mesoderm, after the appearance of the , forms the meninges. These structures, like the lin- ings of the serosal cavities, are composed of connective tissue overlaid by a single layer of epithelium. While attempts have been made to relate the meninges to mesenchyme or to neurectoderm rather than to mesothelium, the histologic structure of these membranes is similar to that of the serosal linings, showing a combination of epithelial and fibroblastic components. Like meso- 378 FrG 1. PHOTOMICROOKAPI1 Or MESOTLILLIOMA 01 1JiL PLEURA SllOWI\G THE CIIARACTERISTICS OF VAXULARlTY, EPITIILLIAL PROLll1 RATTOY AYD SPINULL-CEI L S4RCOAIA. PATH. NO. 38568

FIG.2. PHOTOMICROGRAPHOF A VASCULAR MENINGEAL TUMOR OCCURRII~G IN A MANOF SIXTYYEARS The tumor perforated both tables of the sltull. Path. No. 53069.

379 3 80 CHARLES F. GESCHICKTER thelium the large flat cells on the outer surface of the pia and on the arach- noidal surfaces may be outlined by silver nitrate. The more undifferentiated neoplasms of the meninges are extremely vascular (Fig. 2). The largest number of mesothelial tumors occur in the meninges; they are benign in character and are variously termed arachnoidal fibroblastomas, dural endotheliomas, and meningiomas. The pleural tumors are next in frequency but are more malignant in character. Tumors of the pericardium and peri- toneum are extremely rare and are similar in behavior to those of the pleura. In the formation of the the primitive mesoderm is carried inwardly with the down-growing epithelium and from it tumors of a mesothelial character are occasionally formed. Metastases are extremely rare among the mesothelial tumors, regardless of location. The following tabulation presents the inci- dence of these tumors in the Surgical Pathological Laboratory of the Johns Hopkins Hospital.

Meningeal tumors ...... 106 Pleural tumors ...... 25 Pericardial and peritoneal tumors ...... 3 Ovarian ...... 2

TOTAL 136

MENINGEALMESOTHELIOMAS Meningeal tumors comprise about one-sixth of the new growths involving the cranial contents. Similar tumors may arise from the coverings of the . The varied terminology applied to these growths reflects the dif- ferences of opinion regarding the origin of the leptomeninges from the meso- derm or neurectoderm and the relation of these neoplasms to the arachnoid or dura. The majority of meningeal tumors are encapsulated growths occurring in adult life. In the present series of 106 cases the peak of age incidence was in the decade between thirty and forty. Sixty-five per cent of the patients were between thirty and fifty years old. The youngest patient was fourteen, the oldest sixty-two. The tumors grow slowly and may remain symptomless for many years. The average duration of symptoms in the present series was two years and a quarter, although a history extending beyond five years was not rare. The growths are most common near the vertex along the longitudinal sinus, in the falx, about the temporal , or at the sphenoidal attachments about the sella turcica. Intracranial pressure (evidenced by headache, vomiting, and impaired vision) and epileptic seizures, usually beginning in the leg or arm, are the most common signs. The intracranial pressure may increase very slowly and the headaches may be relatively mild in character. Tumors near the longitudinal sinus produce convulsions, usually beginning in the arm or leg, and motor aphasia. Changes in personality may occur. Lesions in the falx are characterized by weakness in the leg or clonic seizures in this extremity. The roof of the corresponding ventricle appears depressed in the ventriculogram. Neoplasms arising near the clinoid processes of the MESOTHELIAL TUMORS 381 sphenoid or the lesser wing produce blindness and may be characterized by primary atrophy of the optic on the affected side and choked disc on the opposite side. The lesions in the olfactory groove produce anosmia and uncinate attacks. The symptoms associated with spinal meningeal tumors vary with the level of the cord compressed. Paraplegia and bladder dis- turbances are outstanding. The locations of the tumors in the present series were as follows:

Frontal region ...... 30 Region of falx ...... 18 Temporal and middle fossa ...... 15 Spinal meninges ...... 10 Pontine angle ...... 7 Parietal region ...... 4 Occipital region ...... 4 Suprasellar region ...... 4 Sphenoidal region ...... 4 Multiple ...... An interesting feature of these meningeal tumors is the variety of changes produced in the cranial bones. In the roentgenogram may be seen markings produced by increased vascularity, clearly demarcated areas of bone resorp- tion, and centers of calcification. In about 10 per cent of the cases cranial osteophytes or hyperostoses are produced by invasion of the bones; the tumor passes through both inner and outer tables and produces radiating spicules of new bone from both. Such cranial involvement must be differentiated from benign osteomas, which arise during childhood, produce mound-like swelling over the outer table and depress but do not invade the inner table, In the present series there were 10 cases of hyperostoses produced by meningeal tumors. These and 18 similar cases gathered from the literature have been analyzed by Echlin. In some instances the new bone production was not discovered until operation. In these cases the average duration of symptoms at the time of operation was five years or about twice as long as the average for the entire series. The bones involved, in the order of frequency, were frontal, parietal, frontoparietal and temporal. In 4 cases thickening of orbital plates produced exophthalmos. In approximately one-half of the cases the bone involvement rather than the intracranial growth was the first finding noticed by the patient. Except for the visible and palpable swelling, the symptoms produced do not differ from those of meningeal tumor without bone involvement. While the typical roentgen picture shows spicules of bone radi- ating from both tables, these may be absent in the very early stages, and the bones show only a rounded thickening. At operation the meningeal tumor is found attached to the dura and ex- tending inwardly, pressing upon the brain substance. In the majority of cases the tumor does not extend to the tables of the skull or excite new bone forma- tion in the region overlying the tumor. The tumor itself, however, may be gritty on section, enclosing calcified or osseous areas. The overlying dura and cranium show increased vascularity. The following case is illustrative of the more invasive meningeal tumors producing osteophytes and erosion in the cranial bones: FIG.3. ROENTGENOGRAMOF AN INVASIVEMENINGEAL TUMOR PENETRATING THE SKULLAND PRODUCINGOSTEOPIIYTES IN TIIE CRANIALBONILS. PATH. No. 45782

FIG.4. CZSE SIIOWN IN F~G.3: A VIEW' OF INTERIOROF SKULL;B. SPECIMENSlIOWING RELATIOK OF TIIE TUMORTO THE FALXAND BRAIN Note the erosion of the cranial vault in A. 3x2 MESOTHELIAL TUMORS 383

PATH.No. 45782: The patient was a white male aged forty years. Seventeen years prior to the present illness he was struck on the head by a cable while standing on a moving freight car. He became unconscious, but no fracture of the skull occurred and he returned to work after ten days. One year ago the patient complained of impaired vision. No re- fractive error was found, however; x-ray examination was not done. When seen in June 1925, the prttient complained of double vision noticed two weeks be- fore. His pupils were moderately dilated. There was weakness in the right external rectus muscle. X-ray examination of the skull showed a tumor with radiating bone spicules in the right parietal region. The osteophytes radiated from both tables. There was also an erosion of the posterior clinoid processes with enlargement of the sella turcica.

FIG.5. PIIOTOMICROGRAPHOF THE TUMORIW CASESI~OWN IN Frcs. 3 AND 4 Note the acinar arrangement of the epithelial elements and the vascular spaces.

On his first admission to the clinic, in June 1928, the patient had bifrontal headache, dizziness, pain in the leg, paresthesias in the right hand and right foot, clonic seizures of the right arm, impairment of speech and bladder disturbance. Examination showed impaired vision in both , bilateral papilledema, some weakness of the right side of the face, and weakness in the right upper and lower extremities. The x-ray picture of the skull was similar to that taken prior to admission (Fig. 3). On July 9, 1928, craniotomy was performed. The skull showed a vascular semi-solid mass which was interpreted as a malignant change in bone over an extensive parasagittal meningeal tumor. Complete removal of the tumor was not attempted. Following discharge from the clinic the patient returned to his occupation and continued to work for two years. The mass on the surface of the head continued to grow, but was partially controlled by deep x-ray therapy. In the next two years the patient became steadily worse. His vision failed. Cerebrospinal fluid was discharged through the left 3 84 CHARLES P. GESCHICKTER nostril and the left side became paralyzed. Death occurred on Aug. 22, 1932, four yrars after the onset of the illness. At autopsy ;L tumor was found immediately beneath the scalp; the mass passing through the prietal bone was about 4 inches in diameter (Fig. 4A). The tumor pene- trated the dura about the superior longitudinal sinus and infiltrated the right cerebral hemisphere (Fig. 4B). It was firmly attached to the falx cerebri and bulged into the left hemisphere. The cribriform plate of the left ethnioid was eroded and there was a hernia of the meninges in this area. The sella turcica was enlarged but its surface was smooth. No metastases were found. Microscopically the tumor was composed of spindle cells arranged in whorls about centers of hyalinization or calcification. Sections taken from the skull showed bony frag- ments and spicules of new bone surrounded by osteoblasts. The bony structures were in- terspersed with tumor tissue (Fig. 5). Microscopically meningeal tumors are characterized by epithelial-like cells with large nuclei and fairly abundant cytoplasm. These epithelial cells are similar to those found in normal mesothelium (Fig. 6). Other cells, elongated and spindle-shaped, resembling , are usually present (Fig. 7). The tumor cells are arranged in sheets and whorls centering about vessels, corpora amylacea, or calcified bodies. Collagen fibrils may be prominent. In the present series of cases approximately 90 per cent of the tumors show the characteristic combination of fibrous and epithelial elements with occa- sional predominance of either fibroblasts or epithelial cells. Atypical forms showing marked ossification, extreme vascularity, or sarcomatous elements comprise less than 10 per cent of the series. Although Bailey has described nine pathologic types of meningeal tumors, the microscopic features of these growths in general are remarkably uniform. In two cases we have observed malignant invasive meningeal tumors composed of small spindle cells and highly vascular. These tumors correspond to the angioblastic or sarcomatous type described in the literature. Ossification is more common. The true osteomas and osteogenic of the leptomeninges are rare, and in such growths it is impossible to rule out a dural origin. As Bailey and Bucy have emphasized, the interpretation of meningeal tumors as arachnoidal fibroblastomas is too narrow. It is inconsistent with their usual epithelial appearance. An origin from the mesoderm is far more plausible. This would account for the epithelial character of most of the growths, which tend to form mesothelium, and for their tendency to form inesenchymal derivatives such as osseous and angiomatous tissue. The treatment of meningeal tumors is surgical. Extirpation of the smaller growths is rarely followed by a recurrence. The more invasive tumors either recur or are inoperable. In many of the cases the large size of the tumor and extreme vascularity make removal difficult and may necessitate a two-stage operation. Cushing reports 260 cases operated upon 489 times with 54 deaths. In 69 cases operated on within a recent three-year period, by electrosurgical methods, there was an 11.6 per cent case mortality. PLEURAL~IESOTHELIOMAS A variety of histologic forms occur in tumors affecting the chest wall. In 1930 Zinninger collected from the literature 238 tumors in this location. The largest group was reported from the Mayo Clinic by Harrington. Cartilagi- FIG. 6. PlIOTOMICROGRAPII OF A fifESINGEAL TUMORSI

F 10. 7. PHOTOMICROGRAPHOF A MENINGEAL TUMOR S~rowrsc A CHARACTERISTICSPINDLE-CEI.L STRtJCTURE ARRANGEDIN WHORLS AND ENCLOSINGCORPORA AMYLACEA. PATH. NO. 33529

385 3 86 CHARLES F. GESCHICKTER nous and osseous tumors arising from the ribs are the most common tumors in this region. Next in frequency are those of the nerve sheath. Fibrosarconias and liposarcomas derived from the pleural mesenchyme are not peculiar to this structure. Klemperer and Rabin have referred to these growths as localized pleural tumors to distinguish them from the diffuse pleural mesotheliomas. Mesotheliomas are among the rare tumors arising from the pleura which show characteristic microscopic and clinical features. Approximately one-seventh of benign and malignant new growths affecting the chest wall originate from the pleural lining cells. In the present series of cases there were 25 mesotheliomas of the pleura.

E’lC. 8. KOENTGENOOHAM OF A PLEURAL TUMOR IN TIIE LOWER LEFT cI€EST Note the bulging of the chest wall and pleural effusion. Path. No. 55720.

Three of these cases have been previously reported by Heuer. All were in adults ranging from seventeen to sixty-six years of age, and all terminated fatally. Only two patients were under thirty years of age. The average duration of symptoms was two years. One patient had been aware of difficulty for only three months, another for more than four years. Following clinical recognition, the disease usually pursues a rapid course, involving the pleura diffusely on one or both sides. Distant metastases are extremely rare, although the mediastinal nodes and the may be affected in the terminal stages, Extension through the diaphragm with involvement of the and is not unconiinon (Fig. 9). The most common symptom is pain in the chest accompanied by bulging or retraction in the painful area. On palpation the mass can be felt either as a region of thickening or as a definite demarcated tumor protruding between MESOTHELIAL TUMORS 387

the ribs or surrounding the bone. Cough, dyspnea, and pleural effusion occur later in the disease. In the roentgenogram the characteristic finding is a dense shadow with its base at the ribs and its apex directed toward the mediastinum. The margins of the shadow are smooth and the base is usually moulded to the contour of the chest wall. In some cases the roentgenographic features suggest a pri- mary tumor of the rib because of the central area of destruction or complete erosion of the bone (Fig. 8). In late cases the tumor shadow is obscured by pleural effusion, or one or more secondary nodules of the pleura may suggest metastases to the chest rather than a primary neoplasm.

FIG.9. DRAWING OF A TYPICALPLEURAL TUMORWITH A DENSETRIANGULAR SHADOW HAVING ITS BASEAT TlIE CHEST WALL AND hEX DIRECTLDTOWARD THE MEDIASTINUM The tumor shadow is partially obscured by pleural effusion. Path. NO.52186.

At operation a localized mass may be found involving the pleura and the overlying structures of the chest wall, including one or more ribs (Fig. 10). In some cases, the entire visible visceral and parietal pleura on the affected side may be involved by a dense, infiltrating mass. The following cases are illus- trative : PATH.No. 44608: The patient was a white man aged forty-four, whose trouble began two years previously following an . There was pain in the region of the upper right chest radiating down the arm. This was accompanied by persistent cough and shortness of breath. X-rays showed dense shadows in the upper right chest and upper two-thirds of the left chest, and destruction of the first and second ribs on the left side. Operation was per- formed for the removal of a tumor surrounding the involved portions of the first and second ribs on the left. Examination of the tumor tissue showed malignant epithelial cells asso- ciated with elongated sarcomatous elements. The greater part of the tissue was necrotic 388 CHARLES F. GESCHICKTER and stained poorly. The patient died two months after operation. Autopsy was not ob- t ained. PATIT.No. 51952: The patient was a white male aged sixty-six, whose symptoms began two months previously. Following a cold, there was pain in the lower right thorax, with shortness of breath, cough, and expectoration. The patient had lost 30 pounds since the onset of his illness. Physical examination showed absence of expansion of the right chest with diminished breath sounds and a dull percussion note. The x-ray showed the right lower chest to be opaque. The upper part of the right showed scattered infiltration suggesting tuberculosis. A massive pleural effusion developed, which necessitated repeated thoracenteses. The patient died two months after admission to the hospital. Autopsy re- vealed a dense gray tumor involving practically the entire right visceral and 1)arietal pleura.

FIG. 10. PLEURAI. MESOTIIELIOMA OCCURRING IN A WOMANAGED FIFTY-TWO,WIIo COMPLAINED OF COlrGH >AND PAlN IN TIIE CIIEST FOR FIVEMONTES The pleural mass has surrounded the sixth rib and has destroyed the bone. Path. No. 43004.

At one point the pleura was 4 cm. thick. The tumor itself measured 30 X 14 X 9 cm. The mediastinal lymph nodes were involved by metastases. Several metastases were found in the upper lobe of the right lung. Microscopically the tumor was a typical mesothelioma of the pleura. PATH.NO. 9456: The patient was a white female aged sixty. In 1921 she had pain in the left chest accompanied by a distressing cough. On examination there was a definite fric- tion rub, and roentgenograms showed a semicircular shadow in the lower lobe of the left lung. The condition was interpreted as an acute pleurisy and after three months the pa- tient apparently had recovered. In 1922, she suffered from weakness, dyspnea, and tachy- cardia. Her symptoms at this time were attributed to hyperthyroidism. The basal meta- bolic rate was recorded as plus 40. The symptoms referable to hyperthyroidism grew worse, and were accompanied by choking spells, hysteria, and loss of memory. A sub- total thyroidectomy was performed in February 1923. While the patient was in the hospital hid accumulated in the left chest and thoracentesis was performed. In the summer of 1023, the condition improved but there were recurrent attacks of stupor and increasing dull- ness to percussion in the left chest. The chest was treated by deep x-ray therapy. In 1924, the patient showed marked mental improvement but repeated tappings were necessary be- cause of the accumulations of fluid in the left chest. In 1925, myxedema developed. There was further loss of memory and attacks of dyspnea were produced by obstruction in the left chest. Death occurred in September 1926. Autopsy revealed a tumor filling two-thirds of the left . The right pleura and pericardium were normal. No tumor nodules were found in the mediastinal lymph nodes and both lungs were uninvolved. The tumor removed with the left lung weighed MESOTHELIAL TUMORS 3 89

1625 grams and measured 18 X 25 X 10 cm. It was adherent to but did not invade the left lung and lateral pericardium. Externally the tumor tissue was smooth, glistening, and en- capsulated. Pedunculated masses 1 to 5 cm. long protruded from the lateral surface. The cut tumor tissue was white, firm, and interspersed with soft yellow lobules. Microscopic examination showed tightly packed masses of plump spindle cells separated by a delicate connective-tissue . Numerous blood vessels penetrated the tumor tissue. No metastatic tumor nodules were found in other organs. There were a small fibroma of the ovary and a small in the kidney. Examination of the brain showed a yel- lowish indurated area beneath the dura overlying the left motor area and extending down- ward on the falx. On microscopic examination this was negative for tumor cells and was interpreted as the remains of an old hemorrhage.

FIG. 11. PHOTOMICROGRAPHOF THE TUMORSHOWN IN FIG. 10 The cells of the tumor are large and resemble epithelium. They hang in clusters about strands of fibrous tissue which divide the tumor into alveolar-like segments.

The microscopic appearance of pleural mesotheliomas may suggest or . Most frequently a diffuse proliferation of spindle and epi- thelial-like cells is found. The spindle cells have the characteristics of fibro- blasts; the epithelial cells suggest those found in meningeal tumors. In some cases the tumor tissue is divided into lobules by dense strands of fibrous tissue, enclosing clusters of large epithelial cells, some of which take on an acinar arrangement (Fig. 11). In a few instances the cells may be extremely small, the majority round, others elongated, suggesting Ewing’s sarcoma. In general, the combination of connective tissue and epithelial elements is characteristic of these growths. Formerly they were designated endotheliomas. Excision was attempted in the majority of cases in the present series. In 4 of the cases operation was performed for one or more recurrences. In 2 of these multiple nodules extending to the remainder of the pleura on the affected 3 90 CHARLES F. GESCHICKTER side were found at the second operation. Apparently none of the patients was benefited by surgery, although in 3 instances the operator was under the impression that the tumor was localized to the rib or the region of the pleura excised. Irradiation produced no apparent improvement. In the majority of instances death occurred in less than a year following treatment, from ex- tension of the tumor to the pleura, lung, or mediastinal lymph nodes. In one instance there were metastases to the brain and in another to the long bones. Involvement of the pleura, the fibro-epithelial structure of the tumor, and the rarity of distant metastases are characteristic of mesotheliomas of the pleura. The tumor cells are derived from coelomic epithelium, a structure which on the one hand is capable of forming glandular epithelium such as is found in the , and on the other of giving rise to fibrous tissue such as is found in the stroma of the ovary. The intimate relationship of the mesothelial cells to primitive coeloniic epithelium accounts for the varied histologic structures found in new growths arising in the pleura.

MESOTHELIOMASOF THE PERICARDIUM AND PERITONEUM Tumors microscopically similar to those occurring in the pleura are found in the pericardium and in the peritoneal structures, including the mesentery and omentum. Pathologic differentiation of primary growths from metastatic tumors is extremely dificult in these locations, and reports of cases which are unquestionably primary are rare. There is one case of mesothelioma of the pericardium recorded in this laboratory.

PATH. No. 7630: The patient was a white male of twenty-eight years who for five months had suffered pain and a of fulness in the left chest, accompanied by dyspnea ant1 the expectoration of bloody sputum. On examination he was dyspneic and cyanotic. The veins over the front of the left chest were dilated. There were signs of fluid in the left chest, and the and were displaced to the right. There was increased retro- sternal dulness, and x-ray examination disclosed a large inediastinal mass, which was clini- cally interpreted as lymphosarcoma. The patient died a few days after admission and autopsy was performed. On opening the chest the left pleural cavity was found to contain 3 liters of dark sanguineous fluid. Neither the right nor the left pleura was involved by tumor. The left lung was collapsed but contained no tumor nodules. A few small scattered nodules of tumor were found in the right lung. In the upper anterior mediastinum was a soft mass about the size of a large grapefruit, extending from the superasternal notch to the hilum of the lung. It passed down around the aorta, and over the upper portion of the pericardium. Both lungs, the trachea, , and the great vessels were pushed backward. The vena cava was obliterated by the mass. The pericardium was adherent to the heart over the entire surface. Both the peri- cnrdium and epicardiuni were diffusely thickened. The pericardial sac was filled by a red mass, varying from 1 to 2 cm. in thickness. On the anterior portion of the heart, the tumor bulged to form a mound 6 cm. in diameter, continuous with tumor tissue invading the medi- astinum. The tumor penetrated the right auricle apparently from the vena cava. The mass in the mediastinum was invested by a tough thin capsule. On incision, a gray red semifluid tissue oozed forth. With the exception of the tumor nodules on the surfqce of the right lung, no other metastases were found. The tumor was composed of a mass of plump spindle cells, some of them elongated and suggesting fibroblasts (Fig. 1.2). These were arranged about numerous small capillaries. Many of the cells were large and polygonal in shape with degenerating or hyperchromatic nuclei. These larger cells had an epithelial appearance. The tumor resembled closely the vLiscul;irmeningeal tumors which have been described in the literature as angioblastic. MESOTHELIAL TUMORS 391

In 1930 Bodon reported a primary tumor of the pericardium.

The pntient was a man of sixty-five years with a diffuse bronchitis. The heart sounds were faint, there was a double diastolic murmur, and the pulse was irregular. The Wasser- mann reaction was positive. X-ray examination showed a mass the size of a fist interpreted as an aneurysm at the arch of the aorta. This overlapped an enlarged heart shadow. The patient died in two weeks with a clinical diagnosis of aortic aneurysm, tabes, and bronchial pneumonia.

FIG. 12. PHOTOMICROGRAPH OF A VASCIJLAR MESOTHELIOMAOF THE PERICARDIUM The tumor filled the pericardial sac and invaded the mediastinurn and the right auricle. Path. No. 7630.

At autopsy there were 1.5 liters of fluid in the pericardium. A firm, reddish tumor was found in the mediastinum. This was composed of confluent nodules which infiltrated the visceral and parietal pericardium. The detached pericardium was 1.5 cm. in thickness. The tumor penetrated the endocardium in the region of the right pulmonic valve and surrounded the root of the aorta. A meningeal tumor was found in the falx at the attachment to the crista galli. Histo- logically the tumor of the pericardium showed round cells somewhat larger than lymphocytes embedded in a reticular and vascular meshwork. The tumor of the falx was a typical meningeal mesothelioma.

Bodon collected 11 additional cases from the literature. He found men in middle life usually affected. The thickening of the pericardial sac was knotty or diffuse. In 3 cases the masses were localized (Chajutin, Redtenbacher, Godel); in 3 cases the entire pericardiuni was involved (Schoppler, Loos, Hill); in two cases the parietal pericardium only was affected (Tobiesen, Wil- 392 CHARLES F. GESCHICKTER liams). Reference is also made to cases of Lazarus, Drysdale and Kaak. In two cases the heart muscle was invaded. Metastasis to the mediastinal lymph nodes occurred once, and to the adrenal once. Two recent cases not mentioned by Bodon may be added, bringing the total number of pericardial mesotheliomas to 15. Everingham reported a case oc- curring in a woman of forty-four, who suffered from cough, precordial pain, and dyspnea, with fever and loss of weight. A mass overlapping the heart shadow and pulsating with each beat was seen under the fluoroscope. At op- eration, which was followed by death nine days later, a mass 12 cm. in diam- eter was excised from the right lateral wall of the pericardiuni. Tarro de- scribed a tumor of the pericardium with an alveolar arrangement of cells and a rich fibrous stroma. It metastasized to the mediastinal lymph nodes. The most frequently reported tumors of the peritoneum are congenital mesenteric . These are solitary or multiple benign lyniphangiomas. Wakely has collected 300 such cases from the literature. They do not belong with the pathologic group of mesotheliomas. The malignant growths de- scribed in the mesentery or oinentum are usually metastatic. Rankin and Major have reported 22 tumors as primary in the mesentery, including 8 sar- comas. Of the 8 sarcomas none were mesotheliomas. The benign tumors were cysts, fibromas, or lipomas. One case of primary mesothelioma of the peritoneum is reported by Laurh. This was in a woman of fifty years with pain and abdominal enlargement of three months’ duration. There were vomiting, weakness, and loss of weight. i\ pleural effusion in the left chest yielded fluid with malignant cells. At autopsy the omentum and mesentery were diffusely thickened, white, and firm. There were three liters of ascitic fluid and numerous adhesions. There were no metastases, but the tumor extended through the diaphragm into the left pleura. Laur&described the sections histologically as carcinoma composed of squamous-like cells arranged in alveolar fashion. His photomicrographs un- fortunately are too poor to permit confirmation of these findings. Sanes and Kenny have reported three primary sarcomas of the great onientum and collected 5 7 cases from the literature. Their third case is histo- logically typical of mesothelioma. It occurred in a woman of sixty-six years who had progressive enlargement of the abdomen for six months, accompanied by hiccoughs and gastric distress. Death occurred suddenly and at autopsy there were twelve liters of hemorrhagic ascitic fluid and a papillary tumor originating in the great omentum with metastatic dissemination to the mesen- tery. In a review of the literature Sanes and Kenny found 54 cases with microscopic description. Thirty of these were forms of (spindle myxosarcoma, etc.). Twelve were described as round- sarcoma and two as endothelial. It is probable that a few of the spindle cell and the endothelial tumors were mesotheliomas. Two peritoneal mesotheliomas are recorded in this laboratory :

PATH.No. 25327: A white male aged forlj-five years had suffered from nervous ex- haustion for six months Pain in the abdomen, constipation, and loss of weight had been observed for two months. Koentgen studies revealed absence of barium in the transverse colon. At operution R huge, lobular, inoperable mass covered by peritoneum was seen ex- tending from the to the duodenum. The tumor covered the and extended MESOTHELIAL TUMORS 393

over the diaphragm. Scattered nodules and dilated vessels occurred along the ileum at its mesenteric attachment. No localized point of origin could be determined. The spleen, , liver, and were apparently uninvolved. Biopsy revealed a tumor com- posed of small polygonal cells and round cells slightly larger than lymphocytes (Fig, 13). The patient died shortly after operation.

FIG.13. PHOTOMICROGRAPHS OF A M~sOTirEL103f.AOF TIIE PERITONEUM Spindle and epithelial cells are embedded in a hemorrhagic stroma. Path. No. 25327. PATH.No. 5926: A white male aged sixty-one had general malaise and swelling of the knees of six months’ duration, followed by intermittent pains in the abdomen. The ab- dominal pains increased in severity, the abdomen became distended and diarrhea followed. There was progressive weakness, with a loss of 50 pounds in weight. On inspection the abdomen was greatly distended, with an indefinite mass in the lower part. The white cell count was 16,350. The clinical impression was tuberculous peritonitis. X-ray examination revealed a filling defect in the duodenum. The irregular configuration of barium in the in- 394 CHARLES F. GESCIIICKTER testine was thought to be produced by adhesions. Coma developed shortly after admission and the patient died. At autopsy the anatomical diagnosis was spindle-cell sarcoma of the mesentery, metasta- sis to liver and spleen, cysts of the intestinal wall, diffuse peritonitis and left hydronephrosis. On opening the abdominal cavity the omentum was found adherent to the . The small intestine was dotted with small white nodules. A mass overlying the bladder in- volved the mesentery of the sigmoid and was adherent to numerous loops of bowel. It ex- tended on either side to the pelvic brim, surrounding the . Microscopically the tumor was composed of clumped spindle and epithelial cells sur- rounding numerous capillaries (Fig. 14). It resembled a vascular form of meningeal tumor and was similar to the tumor arising in the pericardium described above (Fig. 12).

FIG.14. PHOTOMICROGRAPLIOF A MESOTHELIOMA OF THE MESENTRY Spindle and epithelial cells surround numerous capillaries. The tissue resembles that seen in viiscular meningeal tumors. Path. No. 5926.

OVARIANMESOTHELIOMAS The mesodernial tissue of the ovary may rarely give rise to tumors resem- bling the mesotheliomas. These tumors occur in adults and are usually ac- companied by formation. They may be bilateral and the capsule of the ovary shows a characteristic thickening. When the tumor is sectioned the thick-walled cyst is seen to contain one or more nodules or papillary out- growths of tumor tissue within a blood cavity. Microscopically the tissue re- sembles the vascular meningiomas or the mesotheliomas of the pericardium or peritoneum described above. There were two such cases recorded in this laboratory. One of them, in a colored woman aged forty-seven, occurred in bilateral cystic , the cysts MESOTHELIAL TUMORS 395 having firm, solid walls of tumor tissue. Transplants studded the and the peritoneal surfaces. The patient was still living one and one-half years after the operation. The second patient was a woman aged sixty years. A

FIG. 15. PHOTOMICROGRAPHS OF A MLSOTHELIOMAOF THE OVARY. PATII. NO. 49712 large containing sanguineous fluid replaced the left ovary. The cyst wall was uniformly thick and from one surface a large papillary tumor projected. The patient died postoperatively. The microscopic structure of these tumors is illustrated in Fig. 15. 3 96 CHARLES F. GESCHICKTER

I~IRLIOGRAPHY

BAILEY,P., AND UUCY,P. C.: Origin and nature of meningeal tumors, Am. J. 15: 15, 1931. BODON,G.: Ein Fall von prim;irem Sarkom dcs Perikards, Frankfurt. Ztschr. f. Path. 40: 431, 1030. (Cites 11 cases from literature, with references.) CUSHINC,H.: Tumors of the Brain, Charles Thomas, Baltimore, Md., 1931. ECHLIN, F. : Cranial osteomas and hyperostoses produced by meningeal fibroblastomas, Arch. Surg. 28: 357, 1934. EVERINGHAM,S. : Primary endothelioma of the pericardium, Surg. Clinics North America 11: 975, 1931. HEUER,R.: Circumscribed endothelioma of the pleura, Ann. Surg. 70: 632, 1024. KLEMPERER,p., AND RABIN,C. B.: Primary neoplasms of the pleura, Arch. Path. 11: 385, 1931. LAURA,L.: Su di un caso di carcinoma primitivo del peritoneo, Tuniori 6: 538, 1932. RANKIN,F. W., AND MAJOR,S. G.: Tumors of the mesentery, Surg. Gynec. & Obst. 54: 809, 1932. SANES,S., AND KENNY,17. E.: Primary sarcoma of the great omentum, Am. J. Cancer 21: 705. 1934. TARRO,E.: Sui tumori epiteliali primitivi del pericardio, Arch. ital. di anat. e istol. pat. 1 : 657, 1930. ZINNINGER,M. M. : Tumors of the wall of the thorax, Ann. Surg. 92 : 1043, 1930.