Primary malignant retroperitoneal tumors

REVIEW

Primary

Malignant

Retroperitoneal

Tumors

JAMES R. ARMSTRONG,M.D.AND ISIDORECOHN, JR.,M.D., New Orleans, Louisiana

From the Depwtment of Surgery, Louisiana State Unise&y Meditul Center and Louisiana State University Surgical Service at Charity Hospital of Louisiana, New Orleans, Louisiana.

UMORS of the retroperitoneal area, although

T relatively

uncommon, have assumed increasingly more importance as the surgical attack on abdominal cancer has increased in tempo. These tumors must be included in the differential diagnosis of any abdominal mass, and they may be identified with a high degree of accuracy by the proper use of certain diagnostic examinations which are at the disposal of clinicians. The retroperitoneal space is defined as that area between the peritoneum and posterior parietal wall of the abdominal cavity. It is bounded superiorly by the diaphragm and inferiorly by the pelvic brim Primary retroperitoneal tumors arise within this space and are considered to exclude tumors arising from retroperitoneal organs such as the kidneys, pancreas, and adrenal glands. Similarly, metastatic tumors secondary to neoplasms arising elsewhere in the body are excluded. These tumors have no apparent connection with any adult structure and may arise from the embryologic urogenital cell ridge, areolar connective tissue, adipose tissue, lymph glands, lymphatics, fascia, and sympathetic nervous system structures [I]. Thus, the wide variety of tumors which may be encountered should be understood. Although the first description of retroperitoneal tumors is credited to Morgagni in 1761 [I], the next 100 years brought little advance in the knowledge of tumors in this area. Prior to 1880 retroperitoneal tumors were usually

TABLEI HoSPrTALADMISSIONS ANDTOTAL VERSUS

PER

CENT

Data

Hospital admissions Total malignancies

MALIGNANCIES OF RETROPERITOSEAL TUMORS

No. of

Patients 980,048 25,64i

Per cent of Retroperitoneal Tumors 0.004 0 If

diagnosed as either sarcoma or pancreatic cyst. After this date, however, the number of reports began to increase and an ever expanding classification began to evolve. Approximately 80 per centof retroperitoneal tumors are malignant, with distant metastases being present in one third of these patients at diagnosis. Although malignant tumors of the retroperitoneum represent only a small fraction of the total number of malignancies encountered (Table I), their importance must not be discounted. MATERIAL

The Tumor Registry at Charity Hospital records ~5,617 malignant neoplasms from 19-18 through 1962. An attempt is made to follow up the cases on a yearly basis, and only 0.3 per cent are lost to follow-up study. Of this large number of malignant tumors, only forty-one have been classified as primary retroperitoneal tumors. (Table II.) ,411 patients included in this series had microscopic confirmation of their diagnosis. In thirty-four patients the diagnosis was confirmed by examination of tissue obtained at laparotomy. In the remaining seven the diagnosis was established at autopsy. The survival times of all patients in this series are known up to June 1964. The most common tumors of the retroperitoneum

Armstrong and Cohn

938 TABLEII RETROPERITONEAL TUMORS Tumor

No. of Cases

Lymphoma Neuroblastoma Liposarcoma Leiomyosarcoma Malignant schwannoma Undifferentiated sarcoma Fibrosarcoma Rhabdomyosarcoma

16 6 6 5 4 2 1 1

are the lymphomas, that is, lymphosarcoma, Hodgkin’s disease, and reticulum cell sarcoma. Most series place lymphomas first, but the order of frequency after this is subject to disagreement. Table III, adapted from Melicow [2], lists the malignant tumors which may be found in the retroperitoneum and their tissue of origin. The relative frequency with which the individual tumors appeared herein does not seem to be significantly different from other series. One noteworthy difference, however, was the paucity of undifferentiated sarcomas. While in other series up to 27 per cent of the retroperitoneal malignancies were so classified, only two such tumors appeared at this Hospital. TABLEIII* TISSUE

OF ORIGIN

OF

MALIGNANT

RETROPERITONEAL

TUMORS

Tissue of Origin Fibrous Adipose Mucoid Muscle Vascular Mesenchymal Lymphatic Mesothelial Nerve

Extra-adrenal chromaffin tissue Cell rest Gland tissue Reticuloendothelial

Malignant Tumor Fibrosarcoma Liposarcoma Recurrent myxoma Leiomyosarcoma, rhabdomyosarcoma, and myoblastoma Hemangioendothelioma Malignant hemangiopericytoma Mesenchymoma Lymphangiosarcoma, lymphosarcoma, Hodgkin’s disease, and reticulum cell sarcoma Malignant mesothelioma Partially differentiated ganglioneuroma, sympathicoblastoma, chordoma, and malignant schwannoma Malignant extra-adrenal pheochromocytoma, and ( ?) malignant nonchromaffin paraganglioma Teratoma Adenocarcinoma Xanthosarcoma

* Adapted from Melicow [2].

Most retroperitoneal tumors occur in patients in the later years of life (Fig. l), which is not unlike the majority of malignancies arising elsewhere. This statement excludes neuroblastomas, which usually occur in children, six of which in the present series occurred in children under the age of ten years. The over-all number of male to female patients was twenty-five to sixteen (5 : 3). The sex distribution for each tumor in this series is depicted in Figure 2. No racial differences were encountered. Other series have also failed to correlate race, climate, genetic, or geographic factors with the frequency with which these tumors are encountered [3]. DIAGNOSIS Patients with a retroperitoneal tumor may have a variety of symptoms. The most common initial symptoms observed in this series were weight loss and abdominal enlargement. Several presented with a specific mass in the abdomen or flank. Aside from these complaints, a mass in the retroperitoneum may cause symptoms in a variety of ways. Since the tumors enlarge in the

direction of least resistance, that is, anteriorly, the encroachment upon the abdominal viscera produces their varied symptoms. Pressure on the stomach or duodenum may cause upper gastrointestinal symptoms such as nausea, vomiting, or a sense of fullness. Occasionally jaundice is noted after compression of the common duct. Back pain may progress to radicular type pain as nerve roots are involved by compression or direct extension. Urinary frequency may be a problem if the bladder has been compromised. Ureteral obstruction is not uncommon, with resulting hydronephrosis and possibly uremia. Hematuria may occur as a result of involvement of any portion of the genitourinary tract. One patient in this series, a twenty-six year old Negro woman, was admitted with small bowel obstruction and operated upon because of a diagnosis of incarcerated internal hernia. Laparotomy revealed a nonresectable liposarcoma involving the mesentery of the small bowel. The diagnosis of retroperitoneal tumor may be suspected by physical examination. It may be confirmed preoperatively by radiologic examinations such as the following. 1. Anteroposterior and lateral views of the abdomen (including kidneys, ureters, and bladder). These often will show a soft tissue American

Jouvnal

of Suwery

Primary

Malignant

Retroperitoneal

!):
Tumors

Neuroblastoma L iposarcoma Leiomyosarcoma Malignant Schwannoma 10

FIG. 1. Incidence tumors.

20

30

of primary

40

50

malignant

60

70

00

Undifferentiated Sarcoma motel

F i brosarcoma

retrlq)critoneal

Rhabdomyosarcoma

female=

D

i mass, and its position may suggest a retroperitoneal origin. 2. Upper gastrointestinal series. When a mass is present in the superior portion of the retroperitoneal space, the stomach and/or duodenum will be displaced. The displacement is usually either anterior or upward and to the right. No diagnostic pattern is noted, however, and it is the displacement per se which is of importance. 3. Barium enema. The principle of displacement is again of primary importance. The retroperitoneal portions of the colon are susceptible to compression and/or displacement by a mass in the inferior portions of the retroperitoneal area. Alterations in the normal position of the transverse colon are less important in establishing the diagnosis of retroperitoneal tumor. 4. Intravenous pyelography. This is a particularly important diagnostic tool. The kidneys may be displaced or show decreased or unilaterally absent function. Since the ureters are firmly attached to the posterior peritoneum, their normal course is quickly altered by the presence of an expanding mass in the retroperitoneum. They may be displaced anteriorly or to either side. 5. Retrograde pyelography. This should be undertaken when one kidney fails to be visualized or there is persistent failure of the ureters to be visualized. It is of particular importance to obtain lateral as well as anteroposterior views when these studies are being utilized to detect a retroperitoneal mass. If a preoperative diagnosis of a Vol.119. December 1965

i

i;

s

lb Ii

No. of Potients FIG.

2.

Distribution

of patients

by sex.

retroperitoneal mass is possible, it probably can be made by utilization of these five examinations. Additional information may be afforded by other radiologic examinations such as perirenal air insufflation aerograms, retroperitoneal studies, abdominal aortography, and abdominal venography. Aortography and perirenal aerograms, for instance, may differentiate between retroperitoneal tumors arising in the lumbar areas and primary tumors of the kidneys. None of the patients in this series was studied by these methods. Since the patients in this series were hospitalized over a period of fourteen years and studied on different services, there was no uniformity in the diagnostic work-up. In the past nine years, however, increasingly more patients have been studied radiologically in the Retrogrode Upper Barium

G.I.

enema

I .V.P KUB

lb

io ti

40 5’0 $0

io 80

$0 I60

% of Potients Undergoing Exominotions FIG. 3. The percentage of patients in this series who underwent the five most important diagnostic radiologic examinations.

Armstrong

940

and Cohn

TABLE TREATMENT

Diagnosis

Lymphoma Neuroblastoma Leiomyosarcoma Liposarcoma Malignant schwannoma Undifferentiated sarcoma Fibrosarcoma Rhabdomyosarcoma

OF RETROPERITONEAL

No. of Patients

TUMORS

Average Survival (mo.1

CHARITY

KO

Therapy

HOSPITAL

Surgery * Alone

OF LOUISIANA

X-Ray Therapy Alone

Surgery* and X-Ray Therapy

16 6 5 6

6 47 8 68

5 1 2 0

4

7

2

0

0

2 1 1

9

0 0 0

1 0 0

1 0 0

* Refers to surgery for cure or palliation;

diagnostic

manner previously outlined herein. (Fig. 3.) Excluded from this group are eighteen patients who either died before the work-up was completed, underwent emergency operation, were operated upon elsewhere, or for any other reason failed to receive their entire diagnostic and therapeutic course at this institution. TREATMENT

IV AT THE

AND

RESULTS

Most authors agree that all patients with a known or suspected diagnosis of retroperitoneal tumor require surgery. Exceptions include those patients in whom evidence of metastases is present or who are unable to tolerate surgery. The surgeon must be prepared to perform extensive surgery, for herein lies the best chance for a cure. Thirty-four patients underwent laparotomy, and twenty, or 60 per cent, of these were found to be nonresectable. Twelve, or 64 per cent, of the patients who underwent elective surgery after completion of their diagnostic work-up had a correct preoperative diagnosis of retroperitoneal tumor. The majority of these patients had undergone three or more of the diagnostic radiologic examinations mentioned earlier, indicating the high degree of diagnostic accuracy which may be achieved. Another series reported a 60.5 per cent incidence of correct preoperative diagnosis utilizing radiologic means alone [4,5]. There has been no standard form of therapy in the treatment of retroperitoneal tumors at our institution. (Table IV.) Although 83 per

laparotomies

are excluded.

cent of our patients underwent laparotomy, palliative resection was performed in many cases, and in only four cases did the surgeon believe that he had completely excised the tumor. Three of these four patients received no postoperative therapy while one was treated with irradiation. These four cases represented four different types of tumor: malignant schwannoma, fibrosarcoma, lymphoma, and liposarcoma. Comparison of the survival times of these patients with those of others with the same diagnosis in whom incomplete excision and other forms of therapy were utilized (Table v) reveals that an improved prognosis may be obtained when the surgeon judges that complete excision has been accomplished. It would further suggest that this is the most important prognostic factor. Exceptions exist, for the two longest survivals in the series (each over fourteen years in a patient with liposarcoma and one with neuroblastoma) occurred when only incomplete extirpation of the tumor had been accomplished. The treatment employed for the various tumors reported herein did not differ greatly from those undertaken elsewhere. The specific treatment for the various neoplasms will be discussed in the succeeding paragraphs. Lymphoma. There were sixteen lymphomas. The term, lymphoma, used herein is inclusive of Hodgkin’s disease, lymphosarcoma, and reticulum cell sarcoma [S]. The wide variety of therapeutic measures is indicated in Figure 4. There was no evidence that one form of therapy American

Journal of Surgery

Primary

Malignant

Ketroperitoneal

Sitroger? Mustard, C~xtisonc, and Mcticortell

S-Ray Therap) and Lcukera 11

Sitrogcn Mustard

!)-I I

‘l‘umors

0 0 0 0

0

COMPARISOS

OF SURVIVAL

0 0 0

0 0 0

0

1

I)

0

0

0 0

0

I) 0 0

TABLEV TIMES

AFTER

COMPLETE

EXCISION

VERSUS

INCOMPLETE

EXCISIOS

AND

OTHER

FORMS

OF

THERAPY

Patient

w. s.

M. G. J. c. ,4. A.

Diagnosis Fibrosarcoma Malignant schwannoma Liposarcoma Lymphoma (Hodgkin’s)

* This average was elevated complete escisi~u~s.

Average

Survival

Excision Excision

2 yr. 7 *no. 1 yr. 4 mo.

Only one patient 7 mo.

Excision Excision and x-ray therapy

1 yr. 9 mo. 1 yr. 7 mo.

5yr.8mo.” 6 mo.

by one patient

who survived

superior to any other. No patients are alive at this time, and the average survival was only six months. hIost surgeons recommend excision of the tumor only if it is easily feasible or the tumor definitely appears unicentric in origin [4,5]. Gall [7] claimed a longer survival for those patients treated surgically than for those treated by radiotherapy alone. Irradiation or chemotherapy should follow surgical excision. Radiotherapy should be used in all cases for this usually results in marked diminution in the size of the tumor and alleviation of symptoms. Neuroblastnma. The best form of treatment appears to be surgical excision followed by immediate postoperative irradiation. In the event the tumor is nonresectable, palliation may be anticipated with irradiation alone. Of the six patients with neuroblastoma in this series one had no definitive therapy, two had irradiation alone, one had surgery and postoperative irradiation, one had surgery, x-ray was

Survival

Treatment

fourteen

years and eight months

after multiple,

in-

therapy and vitamin Blz, and one had irradiation and chemotherapy. The average survival was forty-seven months although one is surviving fourteen years nine months after incomplete excision and postoperative irradiation, and another is alive eight years after diagnosis, having been treated with x-ray therapy and vitamin B12. Leiomyosarcoma. The average survival for the five patients in this series was eight months, and the longest was seventeen months. Two patients were treated with surgery alone, one with x-ray therapy alone, and the remaining two received no therapy. Pack and Tabah [3,5] reported surgical excision as the treatment of choice. They recommended partial resection and intensive postoperative irradiation if the tumor was nonresectable. One of their patients was alive four years after radical resection while another was alive thirty-seven months after radical excision and irradiation

Armstrong

942 (No

therapy

1

FIG. 4. An illustration of the wide variety of therapeutic measures utilized in the treatment of the lymphomas. for recurrence. Golden and Stout were of the opinion that x-ray therapy had no effect on these tumors [8]. LiFosarcoma. This neoplasm probably has the best prognosis of all malignant retroperitoneal tumors. The average survival in this series was sixty-eight months, one patient having survived over fourteen years. The treatment of choice is surgical excision [9,10]. Partial excision and irradiation should be employed when the tumor is nonresectable. Recurrences may be treated by re-excision, irradiation, or both. Malignant Schwannoma. Of the four patients with this diagnosis two had surgery alone and two had no therapy. The average survival was only seven months, but one patient survived sixteen months after what was thought to be complete excision. Surgical excision is the preferred form of therapy since irradiation has little or no effect. Undifferentiated Sarcoma. There were two patients in this category. One was treated with surgery and postoperative irradiation and the other had irradiation alone. There was no significant difference in the survival times of the two, the former surviving eight months and the latter ten months. One series reported an eight year survival with irradiation alone [4,5]. The treatment of choice is excision with postoperative irradiation. Fibrosarcoma. Only one fibrosarcoma was found, and this patient survived two years seven months after surgical excision. The treatment of choice is surgical removal. If complete excision is impossible, postoperative irradiation should be employed for worth while palliation may be anticipated after deep x-ray therapy [11,12]. Although these tumors have a high cure rate when located in an extremity [I,?],

and Cohn the prognosis is far less favorable when the tumor originates in the retroperitoneum. This has been attributed to the more advanced stage of the tumor at the time of recognition and to the anatomic difficulties which prevent the surgeon from performing a sufficiently radical excision. Rhubdomyosarcoma. The one patient was nonresectable and was treated with irradiation and nitrogen mustard, with a six month survival. The best treatment is surgical excision followed by irradiation. Irradiation should be utilized in all nonresectable patients. Although the over-all prognosis for this tumor is poor, one series reported a patient living with recurrence sixty-five months after surgery [4,5]. COMMENTS The preoperative diagnosis of retroperitoneal tumors may be established with a high degree of accuracy by utilization of appropriate radiologic examinations. Further studies are usually superfluous and only contribute to a delay in definitive therapy. The prognosis fbr patients with malignant retroperitoneal tumors is poor. The anatomic location of these lesions is responsible for the fact that the tumors are usually large and well advanced before the onset of symptoms. Similarly, their position often will not allow the surgical excision to be sufficiently radical. However, the outlook is not hopeless for long-term survivals have been obtained. The treatment varies somewhat depending upon the type of tumor, but with the single exception of the lymphomas, radical surgical excision is the generally accepted treatment of choice. Early and extensive surgery offers the only opportunity for a cure, and its importance cannot be overemphasized. Irradiation is the second most important form of therapy. Of the neoplasms represented in this series only the malignant schwannoma fails to respond well to irradiation. A high percentage of all retroperitoneal tumors are radiosensitive. One series [3] reported a 77 per cent radiosensitivity, while Judd and Larson [14] found that in their series of thirty-two tumors, thirty patients responded to x-ray therapy. In general, radiotherapy should be utilized primarily in the treatment of lymphomas, as an adjuvant to surgery in the treatment of rhabdomyosarcomas, neuroblastomas, and undifferentiated sarcomas, and in cases of inopera-

Primary Malignant Retroperitoneal biiity, incomplete excision, and postoperative recurrence. Pack and Tabah [4,5] recommended radiotherapy for the following specific indications: (I) inoperable retroperitoneal tumors, in which there is little else to offer, but good palliation can usually he expected ; (2) postoperative recurrences; (2) incomplete excisions; (4) lymphomas; (5) as an adjuvant to surgery in the treatment of the rhabdomyosarcomas, neuroblastomas, and undifferentiated sarcomas. Chemotherapy, which was used to some extent in eight patients in this series, has not been extensively investigated. Thus far it has proved efficacious only in the treatment of lymphomas. SUMtiARY

The forty-one cases of malignant primary tumors of the retroperitoneum recorded by the Tumor Registry of Charity Hospital have been reviewed. The varied symptoms of these tumors were considered, with weight loss and abdominal enlargement being the most common initial symptoms observed. The best means of establishing a preoperative diagnosis is through the utilization of roentgenograms of the abdomen, barium enema, upper gastrointestinal series, and intravenous and retrograde pyelography. The best form of therapy is surgical excision, with the exception of retroperitoneal lymphomas. Irradiation is helpful in the treatment of lymphomas, in instances of inoperability, postoperative recurrence, incomplete excisions, and as an adjuvant to surgery in the treatment of rhabdomyosarcomas, neuroblastomas, and undifferentiated sarcomas. Chemotherapy produces good results only with lymphomas. Surgical removal of the tumor should be attempted in any patient with a suspected retroperitoneal tumor in the absence of distant metastasis.

Vol. 110,

December

1965

Tumors

!13:5

A4cknowLt?dpzunt: \it’e are indebted to the personnel of the Tumor Registry, Charitv Hospital of Louisiana, New Orleans, Louisian:;, for their assistance. REFERENCES 1.

Prinlary retroperitoneal tuincjrs. A report of 93 cases and a reviewof the litera.ture. S/q. GJnec. b Obst.,83: 705, 1946.

I)OXNELI.V,

Ts. X.

2. MELICOW, M. M. Primary tumors of the retroperitoneurn. .\ clinicopathologic analysis of IA2 cases. Review of the literature and tables of classification. J. Internat. Cdl. Sz~vgeons, 19: 401, 1953. 3. NEWMAN, H. K. and PINCK, B. D. Primary retroperitoneal tumors. A summation of thirty-three cases. Arch. Surf., 60: 879, 1950. 4. PACK, G. T. and TABAH, E. J, Primary retroperitoneal tumors. A study of 120 cases. S&g. Gynur. & Obst., 99 : 209, 1954. 5. PACK, G. T. and TABAH, E. J. Primary retroperitoneal tumors. .%rg. Cynec. & Obst., 99:313, 1954. 6. HERBUT, P. ;\., MILLER, F. A., and ERF, L. A. The relation of Hodgkin’s disease, lymphosarcoma and reticulum cell sarcoma. Am. J. Patlz., 21: 233, 1945. 7. GALI,, E. .4. Surgical treatment of malignant lymphoma. Ann. Surg., 118: 1064, 1943. 8. GOLDES, T. and STOUT, il. P. Smooth muscle tumors of the gastrointestinal tract and retroperitoneal tissues. Surg. Gynec. & Ohst., 73: 784, 1941. 9. MCLAUGHLIN, C. W., JR. and SHARPE, J. C. Malignant fatty tumors of the retroperitoneal region. Report of two cases. Am. J. Surg., 41: 512, 1938. 10. DEWEERD, J. H. and DOCKERTY, M. B. Lipomatous retroperitoneal tumors. Am. J. Surg., 84: 3ui, 1952. 11. MAIJN, M. E., JEWELL, F. C., and DUNNING, W. F. Therapy for soft tiSSUe sarcomas. An esperimental study. Szq. Gynec. & Obst., 83: 653, 19-x. 12. PACK, G. T. and ARIEL, 1. M. Fibrosarcoma of soft somatic tissues. Sz47gery, 31: 443, 1952. 13. IVINS, J. C., DOCKERTY, M. B., and GHORMLE~, K. K. Fibrosdrcoma of the soft tissues of the estremities. il review of seventy-eight cases. Surgery, 28: 495, 1950. 14. JUDD, E. S. and LARSON, L. M. Retroperitoneal tumors. S. Clin. North America, 12: 823, 1933.