0022-5347/80/1234-0556$02.00/0 Vol. 123, April Printed in U.S.A.
THE JOURNAL OF UROLOGY
Copyright© 1980 by The Williams & Wilkins Co.
Clinicopathologi cal Conference RAPIDLY EXPANDING RETROPERITONEAL MASS CARL A. OLSSON,* ENRIQUE SOTO,t STEPHEN GERZOF,t WAUN KI HONG§ NEAL K. ANDERSON 11
From the Departments of Medicine, Radiology, Pathology and Urology, Boston Veterans Administration Medical Center, Boston University School of Medicine and Tufts University School of Medicine, Boston, Massachusetts PRESENTATION OF CASE1
Dr. Neal K. Anderson. A 29-year-old white man was admitted to another hospital, complaining of low back pain several weeks in duration. Six days before this hospitalization he had had an episode of vomiting after a meal and had noticed the gradual onset of dull mid abdominal pain, radiating to both shoulders but relieved by sitting up. Previously he had been in good health except for "hepatitis at age 15". He consumed 1 or 2 beers daily but denied recent alcohol excess or any alcoholrelated disease and had no history of exposure to drugs or medications. Physical examination was reported to reveal an ill-appearing thin man with abdominal distension and a large mid abdominal mass, distinct from liver and spleen and fixed posteriorly. There was direct tenderness to palpation over the mass, without rebound tenderness. Laboratory data revealed a hematocrit of 39 per cent and a serum lactic dehydrogenase level of 840 mU./ml. (normal 100 to 250). Serum amylase was normal. AB-mode abdominal sonogram demonstrated a mid abdominal mass with cystic and solid components located retroperitoneally in the region of the pancreas and a repeat scan 6 days later revealed growth of the mass, which now measured 15 X 17 X 7 cm. An upper gastrointestinal series and barium enema were reported as normal and there were no calcifications in the abdomen. An excretory urogram (IVP) revealed obstruction of the right ureter with hydronephrosis. A double dose oral cholecystogram was visualized faintly but normal. The patient was treated with nasogastric suction for a presumed pancreatic pseudocyst. Because of little symptomatic improvement and clinical evidence of rapid growth of the mass the patient was transferred to the Boston Veterans Administration Medical Center 37 days after the hospitalization. On admission to this hospital he was a pale young man, complaining of weight loss and constant dull mid abdominal pain with persistent nausea and vomiting. He denied hematemesis, melena, urgency, frequency and dysuria. His mother and sister had undergone cholecystectomy but there was no family history of cancer. Physical examination revealed a cachectic non-icteric man with blood pressure 140/90, pulse rate 96 respiratory rate 18 and temperature 98.6F. The skin was unre~ markable and there was no lymphadenopathy. Head, neck, chest and cardiac examinations were within normal limits. Abdominal examination revealed distension and decreased • Professor and Chairman, Urology Department, Boston University School of Medicine. t Assistant Director, Pathology Department, Boston University Medical Center. t Chief, Ultrasonography and Body Computed Tomography Boston Veterans Administration Medical Center. ' § Chief, Medical Oncology, Boston Veterans Administration Medical Center. II Resident in Internal Medicine, Boston Veterans Administration Medical Center. 1 Case presented at Medical Oncology Grand Rounds, Boston Veterans Administration Medical Center, April 5, 1978.
bowel sounds. There was marked tenderness in the epigastrium in the right upper quadrant without rebound tenderness. An upper abdominal mass right of the midline measured 15 x 8 cm. and was fixed to underlying tissues. There was no hepatosplenomegaly. The genitalia were unremarkable and the rectal examination was normal with guaiac-negative stool. There was no clubbing, cyanosis or edema of the extremities and the neurological examination was normal. Admission laboratory data showed a hematocrit of 42 per cent, with a white blood count of 7,200 per mm. 3 (68 polymorphonuclear cells, 21 lymphocytes, 9 monocytes and 1 eosinophil). The prothrombin time was 12.6 seconds, with a control of 10.4 seconds, and the partial thromboplastin time was 32 seconds, with a control of 31 seconds. Urinalysis showed a protein of 1+ and a specific gravity of 1.020. There were 1 to 3 white and 1 to 2 red blood cells per high power field. Serum creatinine blood urea nitrogen and electrolytes were normal. The seru~ glutamic oxaloacetic transaminase was 101 mU./ml. (normal 3 to 37) and the lactic dehydrogenase was 1,011 mU./ml. (normal 90 to 200). Serum bilirubin was 1.8 mg. per cent (normal 0.2 to 1.2) and the alkaline phosphatase was 98 mU./ml. (normal 17 to 78). Serum amylase was 70 Somogyi units (normal 40 to 140) and the total protein was 6.3 mg. per cent, with an albumin of 3.1 mg. per cent. Calcium was 8.6 mEq./1., with a phosphorus of 3.7 mg. per cent and urate level of 6.6 mg. per cent. An admission chest x-ray and electrocardiogram were normal. aFetoprotein, /3-subunit human chorionic gonadotropin and carcinoembryonic antigens were obtained. An abdominal sonogram, computerized tomography (CT) scan and superior mesenteric artery arteriogram will be reviewed by the radiologist. Exploratory laparotomy was done 7 days after admission to our institution. DIFFERENTIAL DIAGNOSIS
Dr. Carl A. Olsson. In summary this patient presented with a mid abdominal painful mass, presumably arising from the retroperitoneum. Doctor Gerzof will present his interpretation of the detailed radiologic investigations that were done. Dr. Stephen Gerzof. An abdominal CT scan was done with the patient in the right lateral decubitus position because extrinsic compression and obstruction of the inferior vena cava by the tumor were noted when the patient assumed the supine position. At the level of L4 with infusion of urographic contrast material the CT scan shows selective enhancement of the periphery of the mass, indicating presence of vascular perfusion (fig. 1, A). The central portion of the mass does not enhance with contrast material, indicating that it is avascular, cystic or necrotic. The small arrow indicates contrast medium in the left ureter, while the right ureter is not seen. With a high volume infusion technique the non-visualization of a ureter is significant and correlates well with the presence of ipsilateral uropathyin this case obstruction of the right ureter by the mass. Normally, the fascial planes anterior to the great vessels should be
RAPIDLY EXPANDING RETROPERITONEAL MASS
FIG. 1. A, contrast medium enhanced 2½-minute CT scan at level of transverse white line in figure 3, B shows enhancement of vascular periphery (arrowheads) of large retroperitoneal mass (M). Obliteration of tissue planes anterior to aorta, vena cava and psoas muscles (P) indicates extensive retroperitoneal infiltration. Small arrow indicates contrast medium in left ureter with right ureter not opacified owing to obstruction. V-L4 vertebral body. B, transverse sonogram of abdomen at level comparable to part A shows large mid abdominal mass (M) that has complex internal echo pattern composed of highly echogenic foci interspersed with echo-free areas (arrowhead), indicating mixed cystic and solid structure.
demonstrated. Their absence in this scan indicates diffuse retroperitoneal infiltration by the mass. Abdominal ultrasonography shows a large mid abdominal complex mass with multiple internal echoes and irregular borders, again indicating that the mass primarily is solid with central cystic areas (fig. 1, B). One should note the central cystic area with poor transmission of sound. Arteriography and venacavography were performed. A lateral view of the inferior venacavogram shows extrinsic compression of the vena cava extending from Ll to L4 (fig. 2). Collateral venous channels are seen in the lumbar veins posteriorly, indicating physiologically significant venous obstruction. A similar lateral view of the aortogram shows marked elevation of the superior mesenteric artery (fig. 3, A). Since the pancreas is anterior to this vessel a pancreatic origin of the mass is unlikely, unless the mass were to arise from the uncinate process that is posterior to the superior mesenteric artery. There is marked draping of the mesenteric vessels over a large soft tissue mid abdominal mass with no evidence of neovascularity (fig. 3, B). The right kidney is hydronephrotic owing to obstruction of the proximal ureter by the mass. The preoperative radiologic assessment is that of a large solid mass with central necrosis arising in and widely infiltrating the retroperitoneum and the root of the mesentery. Other than the mass and its effect on surrounding structures no other retroperitoneal abnormality is detected by the CT scan, ultrasonography or angiography. A pancreatic origin is unlikely because of the position of the mass relative to the superior mesenteric artery. A primary lymphoproliferative disorder is unlikely since lymphomatous masses usually are homogeneous and free of echo. Although pancreatic pseudocysts can present almost anywhere the internal appearance of the mass by the CT scan and ultrasonography is not consistent with this diagnosis. Therefore, the final radiologic diagnosis is that of a neoplasm originating in the retroperitoneum or mesentery. Metastatic lymphadenopathy could account for the radiologic findings but is less likely. Doctor Olsson. An additional anatomic feature of this lesion is inconsistent with the diagnosis of pancreatic pseudocyst. Pancreatic pseudocysts may, indeed, cause ureteral obstruction, renal axis deviation or caliceal distortion. However, our recent
FIG. 2. Lateral view of inferior venacavogram shows extrinsic compression of vena cava anteriorly from Ll to L4 (arrowheads) by mass. Collateral venous return can be seen posteriorly.
review of these occurrences showed that the right kidney was involved on a single occasion only. 1 There are no clinical points that are inconsistent with this diagnosis, since we have seen pseudocysts in the teenage population despite a negative history for alcohol abuse (and this patient's vague gastrointestinal symptomatology certainly is consistent with pancreatic disease). However, the radiographic and anatomic features already discussed are compelling arguments to search for a different diagnosis. The rapidity of expansion of this mass warrants consideration
Fm. 3. A, selective superior mesenteric arteriogram shows draping of mesenteric vessels over large avascular mid abdominal mass. Note hydronephrosis on right side. Transverse white line indicates plan of cross-sectional images in figures 1 and 6. B, lateral view of aortogram shows marked elevation of superior mesenteric artery (SMA) by large mass immediately caudad to artery.
of the diagnosis of retroperitoneal hemorrhage. There is no history of trauma and coagulation studies showed no hemorrhagic diathesis. The common sources for retroperitoneal hemorrhage (in the patient without bleeding diatheses or anticoagulant medication) are the aorta, followed by the kidney and adrenal gland. The patient certainly is not in the age range when we should consider aortic aneurysmal rupture with any seriousness. Does this patient have a condition usually associated with spontaneous rupture of either the kidney or adrenal? I believe the answer to both organs as a potential source of spontaneous hemorrhage is no. The adrenal gland may rupture spontaneously in association with pregnancy, extensive thermal injury or some forms of sepsis (meningococcemia). Tumors of the adrenal gland, particularly pheochromocytoma, have been implicated as predisposing to spontaneous adrenal rupture. It is clear that our patient is not a candidate for any of these diagnostic options. Spontaneous renal rupture may occur in patients with polycystic disease, extensive hydronephrosis, renal arterial aneurysm or tumors of the kidney. In this case the hydronephrosis probably is secondary to the disease process and not of primary etiologic importance. Renal tumors, particularly angiomyolipoma, are noted for their predisposition to spontaneous rupture and retroperitoneal hemorrhage. The patient has none of the pyelographic features of a renal tumor nor does he have the various stigmas associated with tuberous sclerosis. Spontaneous hemorrhage from a renal artery aneurysm could be a diagnostic possibility were the location of the rapidly expanding mass in the region of the kidney. However, when renal aneurysmal rupture occurs in the younger individual it is most likely to be seen in the pregnant woman. Renal microaneurysms associated with either polyarteritis nodosa or with intravenous amphetamine abuse can lead to renal rupture and hemorrhage. 2 However, the patient has none of the clinical features of a connective tissue disorder and drug abuse was denied. In addition, radiographic studies showed no primary disease in any of these retroperitoneal structures.
With regard to infective disorders of the retroperitoneal tissues non-tuberculous and tuberculous retroperitoneal abscess should be considered. Non-tuberculous abscesses occur primarily in male patients by a factor of 3:1. In the child the etiologic organism is a gram-positive coccus, usually arising from a focus in the tonsils, middle ear or skin. In the adult gram-negative organisms result in retroperitoneal abscesses owing to direct extension of bacteria from inflammatory bowel disease or bacterial metastasis from the lower urinary tract (often resulting from instrumentation). 3 Tuberculous retroperitoneal abscesses usually are associated with tuberculosis or spine and bony destruction of spondylitis often is demonstrated on x-ray studies. Furthermore, tuberculous abscesses often are calcified. Since this case shows none of the prior clinical features consistent with either tuberculous or non-tuberculous retroperitoneal abscesses I would dismiss both of these diagnoses. A major diagnostic consideration in any patient with retroperitoneal disease is idiopathic retroperitoneal fibrosis. 4 While patients with this condition may present with anorexia and weight loss they often have flank or back pain as opposed to abdominal pain. Furthermore, they present with an abdominal mass in only 10 per cent of the cases. The laboratory findings usually seen with retroperitoneal fibrosis are not present in our case. The patient did not have anemia, elevated white blood cells or elevated sedimentation rate. There was no mention of elevated globulins or positive blood tests for various connective tissue diseases (antinuclear antibody, smooth muscle antibody or lupus factor) that are associated with retroperitoneal fibrosis. Further points against this diagnosis are the location of the mass (situated well above the classical position at the sacral promontory) and its rapid growth-a phenomenon inconsistent with the indolent course of a fibrotic process. Thus, we are left with the possibility of a retroperitoneal neoplasm. Primary retroperitoneal tumors are malignant in 75 per cent of the cases and affect male subjects by a factor of 2:1. The average age of incidence is 42 years but there is a wide age
RAPIDLY EXPANDING RETROPERITONEAL MASS
range (25 to 75 years) depending, to some extent, on the tissue of origin of the tumor. Presenting symptoms include abdominal pain (in 85 per cent of the cases), weight loss and anorexia. A mass (sometimes discovered on self-examination) is present in 80 per cent of the patients. Because of inferior vena caval involvement lower extremity edema or hydrocele formation may be detected. Femoral nerve entrapment may lead to symptoms of femoral neuropathy. If the gastrointestinal tract is involved diarrhea and bloody stool may be presenting symptoms. If the urinary tract is involved there may be flank pain associated with hydronephrosis. 5 I will not discuss the benign tumors of the retroperitoneum since the clinical course does not seem consistent with these. With regard to malignant retroperitoneal tumors a third are of lymphatic origin and usually are lymphosarcoma, Hodgkin's disease or reticulum cell sarcoma. In these latter diseases there often: is associated splenomegaly or peripheral adenopathy, and bony or pulmonary metastases are not uncommon. Since none of these features pertains to our patient I would favor a diagnosis of a retroperitoneal malignancy of a different cellular origin. Retroperitoneal malignancies of neurogenic origin include neuroblastoma. This patient is not in the age range when this possibility would be entertained. Furthermore, the mass did not have radiographic features, such as calcification, associated with neuroblastoma. Tumors of connective origin include liposarcoma, leiomyosarcoma and rhabdomyosarcoma. These conditions usually are seen in patients at the extremes of age and this patient would be an unlikely candidate for these diagnoses. Tumors of germ cell origin may arise in the retroperitoneum from an undescended testis or by metastasis from a hidden focus of cancer in a scrotal testis. In rare instances a primary focus of germ cell cancer can be found in the retroperitoneum in patients with no history of cryptorchidism and no detectable primary lesion in the normally situated gonads. It has been estimated that approximately 1 per cent of the men with germ cell cancer have primary lesions in a location usually considered a metastatic site. However, careful studies in such patients will demonstrate that some actually have a primary lesion in one of the normally descended testes. These primary lesions may be as small as 1 mm. in diameter. Other patients will have areas of scar formation (representing degenerated healed primary malignancies) in the scrotal testes. Thus, many times the initial diagnosis of extragonadal primary germ cell cancer is erroneous and a lesion is found in the testis at some later point in time (as long as 8 years after the diagnosis of extragonadal germ cell cancer). 6 Documented extragonadal germ cell cancers can be explained by 1 of 2 possible theories. In 1934 Staemmler proposed that failure of primordial germ cells to migrate from the urogenital ridge to the scrotum left a residuum of these cells that might undergo malignant transformation. 7 In 1946 Schlumberger proposed an alternative premise, stating that the primitive totipotential cells are left behind in various anatomic sites during the blastula/morula stage of embryonic development. 8 The usual site of primary extragonadal germ cell tumors is in the retroperitoneum. Other locations include the mediastinum (particularly the thymus), pineal gland, bladder, prostate, stomach and omentum. The criteria for establishing a definite diagnosis of primary extragonadal germinoma (as opposed to metastasis from a normally descended testis) include the finding of non-neoplastic gonadal tissue adjacent to the retroperitoneal tumor or else the finding of an encapsulated tumor without any lymph node involvement. It has been suggested that a germ cell tumor found in a lymph node without any lower retroperitoneal lymph node involvement would qualify for the diagnosis of primary extragonadal germinoma. However, it is common experience that testis tumors metastasize to higher retroperitoneal lymph nodes initially, with centrifugal spread from the initial metastatic focus. Therefore, this last criterion of node
involvement without any disease in the lower retroperitoneal nodes should be discarded. Certainly, the diagnosis of a primary retroperitoneal germ cell tumor is quite likely in this patient. He is in the age range when germ cell tumors occur. The location and radiographic findings are consistent with the diagnosis, as is the clinical presentation. The rapid expansion of the mass can be explained by rapid tumor growth or tumor necrosis with internal hemorrhage. Therefore, my provisional diagnosis in this patient is primary retroperitoneal germinoma. CLINICAL DIAGNOSIS
Retroperitoneal liposarcoma. DOCTOR OLSSON'S DIAGNOSIS
Primary extragonadal germinoma. HOSPITAL COURSE
Doctor Anderson. The patient underwent abdominal exploration and a large retroperitoneal mass was found extending from the mesenteric root to the pelvis, infiltrating the retroperitoneal musculature as well as the small bowel mesentery and great vessels. Aspiration of large cystic areas yielded a bloody, gelatinous material. Because of inability to do a total resection drains were placed in the wound cavity after a debulking excision of the majority of the mass. PATHOLOGY DISCUSSION
Dr. Enrique Soto. The mass removed weighed 1,100 gm. and showed extensive evidence of hemorrhage and necrosis on gross inspection. Many histologic sections were taken. In numerous areas of the mass viable tissue was seen only around blood vessels. A variety of histologic patterns was noted. Sheets of clear cells with distinct borders and prominent nucleoli (fig. 4, A) alternated with glandular areas (fig. 4, B). The cells lining the glandular spaces were either cuboidal or flat. The latter showed a honey-comb pattern (fig. 4, C). An intraluminal basophilic substance was noted in many of the glands. This substance did not stain with mucicarmine. Short papillary projections and occasional glomerular-like formations were observed (fig. 5, A). All of these features are characteristic of the so-called yolk sac tumor or endodermal sinus tumor. These tumors originally were described in the ovary by Schiller in 1939.9 Schiller proposed the designation of mesonephroma for the lesion since he believed the papillary structures represented mesonephric glomeruli. 10 Later, Teilum coined the term endodermal sinus tumor because of the similarity of the histologic features to the endodermal sinuses of the placenta of rodents previously described by Duval. n. 12 The experimental work of Pierce and associates gave support to Teilum's concept that this tumor is a form of germ cell neoplasm differentiating in the direction of yolk sac or vitelline structures. 13 Although yolk sac carcinoma was described originally in the ovary tumors with similar histologic appearance have been reported in the testis, particularly in infancy and childhood. 14- 16 These lesions also have been recognized in extragonadal sites, such as the vagina, sacrococcygeal region, pineal gland, anterior mediastinum and retroperitoneum. 11- 21 The tumor usually occurs in a pure form, although it is sometimes associated with other germ cell neoplasms, such as seminoma, embryonal cancer or immature teratoma. 18• 22 - 24 A careful histologic search in any case of germ cell tumor may show that the occurrence of elements of yolk sac carcinoma is far from rare. 25 Yolk sac tumors have attracted interest in the recent literature since most patients have been found to exhibit elevated levels of serum a-fetoprotein. 26- 28 a-Fetoprotein is an a-globulin normally produced by the fetal liver and by the yolk sac. 29 The a-fetoprotein synthesized by yolk sac tumors, as well
Fm. 4. A, sheets of clear cells with distinct boundaries. B, glandular areas show cuboidal lining. C, honeycomb pattern seen in glandular areas with flat cell lining. H & E, reduced from X225.
Fm. 5. A, papillary and glomeruloid structure (Schiller-Duval body). H & E, reduced from Xl75. B, numerous intercellular hyaline droplets
as other proteins (such as serum albumin, pre-albumin and a-1antitrypsin) appear as hyaline droplets found either within the cytoplasm of the cells or in intercellular spaces. This histologic finding appears to be a highly specific feature of these tumors (fig. 5, B). MANAGEMENT
Dr. Waun Ki Hong. Extragonadal yolk sac carcinoma is an extremely rare malignancy. The natural history of the tumor demonstrates an almost invariable recurrence of disease even following extensive surgical removal. The poor prognosis of the tumor recently led to the use of adjuvant chemotherapy or radiation therapy in an attempt to prolong survival. Addition of radiation therapy alone to surgical excision appears to be inadequate because of the tendency of this lesion to undergo rapid dissemination beyond the radiation field. Combination chemotherapy, using cyclophosphamide, actinomycin D and vincristine, has shown some increase in survival when administered as an adjuvant postoperatively. 30 The management of unresectable extragonadal retroperitoneal yolk sac carcinoma has not been reported in the literature. In our patient the initial a-fetoprotein level was extremely high (51,000 ng./ml.). In the immediate postoperative period drain-
age from the tumor bed varied between 1 and 1.5 1. of bloody gelatinous fluid daily. This patient was treated initially with cyclophosphamide, vinblastine, actinomycin D and bleomycin infusion during a 6day period, followed by high dose administration of cis-platinum with mannitol infusion after prehydration (VAB IV protocol). After this induction treatment maintenance therapy was continued with monthly vinblastine and chlorambucil, as well as alternate actinomycin D or doxorubicin every 3 weeks. 31• 32 a-Fetoprotein levels were reduced to 20 ng./ml. and then to 6 ng./ml. after 3 months of chemotherapy. A repeat CT scan of the abdomen revealed a small residual mass (3 X 2 cm.) at this point in therapy (fig. 6). The patient has gained 40 pounds and presently is asymptomatic with no further wound drainage and an excellent performance status. For patients with localized yolk sac tumors in whom complete resection is possible adjuvant chemotherapy, using cyclophosphamide, actinomycin D and vincristine, should be considered. In patients with unresectable tumor or in those individuals with extensive stage II or III lesions aggressive chemotherapy with cis-platinum, bleomycin and an alkylating agent should be used. At this point it is not clear as to whether there is any significant difference between the VAB and VBP protocols. Chemotherapy
RAPIDLY EXPANDING RETROPERITONEAL MASS
Fm. 6. Followup enhances 2-second CT scan 6 months after figure 1, A at comparable level. Tumor has been reduced to 3 x 2 cm. oval mass (M) contralateral to aorta (A) and inferior vena cava (C). Great vessels can now be identified, since widely infiltrating tumor has regressed and vessels are now surrounded by normal retrnperitoneal fat. Orally administered contrast medium opacifies small bowel and distinguishes it from tumor. P-psoas.
should be maintained for at least 2 years and a second look operation (exploring for residual disease) may also be considered.33 Doctor Olsson. I should like to point out 2 additional featurns regarding management of this case. I would totally agree with the need for a second look procedure as outlined by Doctor Hong and I compliment him for his excellent management of this patient. A second consideration pertains to the question of a primary neoplasm present in one or both testes. There is significant controversy regarding the need for ipsilateral or bilateral orchiectomy in cases of primary retroperitoneal germ cell tumors. My own belief in this regard is a quite practical approach. If the retroperitoneal malignancy is a pure seminoma I would favox ipsilateral orchiectomy with step-sections to identify a possible primary source. In patients with non-seminomatous retroperitoneal tumors that are thought to be primary I would not be concerned with exploring either testis. My reason for this approach is that the patient with a non-seminomatous lesion will undergo systemic chemotherapy, usually with a VAB protocol. This being the case the systemic treatment received should be able to obliterate any microscopic focus prnsent in the testis. On the other hand, in patients with seminoma radiation therapy may be chosen as adjunctive treatment and the radiation portal does not include the testes. REFERENCES 1. Heckman, H. H., Clapp, P.R., Lowney, B., Fuchs, J.E. and Olsson,
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