PRIMARY NONFUNCTIONING CARCINOMA OF ADRENAL CORTEX
J. M. SMITH, M.B., F.R.C.S., F.R.C.S.I.
F. B. KEANE, F.R.C.S.
J. D. O’FLYNN, M.CH., F.R.C.S. (EDIN.), F.R.C.S.I.
P. G. COLLINS, M.CH., F.R.C.S.
From the Urological Department, Meath Hospital; and Departments of Surgery, Trinity College, and Jervis Street Hospital, Dublin, Ireland
ABSTRACT - Two cases of nonfunctioning adrenocortical carcinomas are presented. The clinical features, operative findings, and histopathologic appearances are discussed. It is believed that these tumors are difficult to diagnose because of their vague presentation. Intravenous urography with nephrotomography is the most valuable method of detecting these tumors, and surgery remains the best treatment.
Nonfunctioning tumors of the adrenal gland may be classfied as tumors of the adrenal cortex, tumors of the adrenal medulla, hamartomas, and metastatic tumors. Adrenocortical tumors are usually functioning neoplasms that are man- ifested as adrenogenital syndrome, Conn syn- drome, or Cushing syndrome. If there is no evidence of abnormal hormone production, then the tumor is said to be nonfunctioning. Non- functioning adrenocortical adenomas are only rarely identified during a patient’s life but are commonly found at postmortem. A nonfunction- ing adrenocortical tumor that presents in a pa- tient’s lifetime is invariably a carcinoma but these remain rare tumors. A review of the world literature in 1974 revealed only 178 reported cases.1 We herein report 2 additional cases seen during the past year.
Case Reports
Case 1
A thirty-two-year-old housewife presented for investigation of recurrent urinary tract infection and pain in the left loin. Two years previously in another hospital an intravenous pyelogram re- vealed that the upper pole of the left kidney was missing. She had two children aged nine and
seven years, and her symptoms of urinary tract infection began six months after the birth of her first child. This infection had been treated with antibiotics. Past history revealed rheumatoid ar- thritis in October and December, 1976.
No abnormality was found on physical exami- nation. There were no features of Cushing syndrome or abnormal sexual characteristics. Laboratory investigations were as follows: hemoglobin 12.1 Gm./100 ml., white blood cell count 7,400/cu.mm .; urea, electrolytes, calcium, and inorganic phosphate within normal limits; protein 74 Gm. and albumin 39 Gm./L .; serum cortisol (A.M.) 14.0 mg. and (P.M.) 14.5 mg./dl. Chest x-ray film was normal. Intravenous uro- gram revealed a normal right kidney but the left kidney was displaced downward by a large mass which appeared to be separate from the kidney (Fig. 1A). A selective renal angiogram showed a left suprarenal mass with a malignant circulation arising from the superior aspect of the left main renal artery (Fig. 1B).
At operation, the left adrenal gland was ap- proached through the bed of the eleventh rib. The left adrenal was replaced by a well- encapsulated tumor 5 cm. in diameter. The tumor was removed by ligating the blood sup- ply. There was no evidence of spread.
A
Histopathology showed the neoplasm to be composed of adrenocortical cells, some of which resembled normal, others eosinophilic with somewhat vesicular nucleii and many were pleomorphic. Scattered giant cells were seen, with mitoses, and also pseudoglandular forma- tion. There was widespread necrosis and hemorrhage. These features were consistent with an adrenocortical carcinoma.
Progress postoperatively was uneventful. The patient has remained well and tumor-free twelve months later.
Case 2
A thirty-one-year-old milkman was seen in the outpatient department complaining of epigastric pain and weight loss. Previous medi- cal history disclosed an appendectomy in 1966. He had also been investigated at another hospi- tal in 1975 for right hypochondrial pain. A barium meal at that time had been negative. He smoked twenty cigarettes a day and drank beer occasionally.
Physical examination revealed a large smooth mass in his right hypochondrium which moved on respiration and was thought to be his liver. A sinister diagnosis was suspected and investiga- tions were ordered accordingly.
However, two weeks later he was admitted as an emergency with pneumonia. He also com- plained of severe pain in the right hypochon- drium. The mass in his right hypochondrium appeared larger on examination. Laboratory in- vestigations showed a hemoglobin of 11.4 Gm./ 100 ml .; white blood cell count 13,000/cu.mm .; erythrocyte sedimentation rate 60 mm./hour;
B
urea, electrolytes, serum amylase, blood sugar, liver function tests, and midstream urine speci- men were all normal. Prothrombin time was prolonged 16/12. Alpha fetoprotein and Casoni test were negative. Chest x-ray film demon- strated areas of pneumonic change.
Pneumonia responded satisfactorily to antibi- otics. Further investigations included an in- travenous urogram which showed a normal left kidney, but the right kidney appeared to be pushed down from above (Fig. 2A). Selective ar- teriography showed a tumor circulation on cannu- lation of a right adrenal vessel (Fig. 2B).
Hormonal studies included twenty-four-hour urinary estimation of vanilmandelic acid (8.4 mg./24 hr.), 17-oxysteroids (11.8 mg./24 hr.), 11 hydroxycorteroids (7.8 mg./24 hr.), and cortisol (376.2 mg./24 hr.), all of which were within normal limits.
Laparotomy was performed through a right thoracoabdominal incision through the bed of the ninth rib. A large tumor (17 by 15 cm.) was found above the right kidney. The tumor was encapsulated except for some infiltration into the right hemidiaphragm. There were numer- ous vascular adhesions to the liver and inferior vena cava. Despite this, the tumor was excised in toto except for the small area attached to the diaphragm. There was no attachment to the kidney.
Histology demonstrated a pleomorphic tumor with areas of hemorrhage and necrosis consist- ent with an adrenocortical carcinoma. The pa- tient’s initial postoperative recovery was satis-
A
B
R
Angiogram reveals malig-
factory and he was referred for regiona radiotherapy. His condition remained satisfac . tory until three months postoperatively wher chest x-ray film revealed multiple metastasis He was treated with o,p’-DDD (mitotane) with no observable benefit. He deteriorated and died five and one-half months postoperatively.
Comment
Adrenocortical carcinomas both functionin ;; and nonfunctioning are a rare type of malignant: disease with an incidence of about two per mil lion.2 Of the two types, the nonfunctioning vari . ety is much rarer, but it is stressed that thi : term must be used with reservation since many of these tumors, although incapable of formin ;; an excess of active hormones, are capable of forming precursor steroids without hormonal ac . tivity.3 Hajjar, Hickey, and Samaan+ recently reported a study of 32 patients with adrenal car . cinoma. In 23 patients they performed an en . docrinologic workup which included A.M. and P.M. plasma cortisol levels after dexamethasone suppression, twenty-four-hour urinary 17. hydroxycorticosteroids and 17-ketosteroids, total urinary estrogens before and after therapy, and also plasma levels of testosterone and estradiol before and after dexamethasone suppression Seventeen patients had a functional adrenal car - cinoma, but all except one presented with en - docrine syndromes.
Such extensive hormonal investigations were not carried out in our patients, but those that were, together with an absence of any endo- crine syndrome, make it highly likely that both these tumors were nonfunctioning.
Because of the lack of endocrine manifesta - tion, both tumors in these patients presented insidiously. Symptoms were manifested by tumor enlargement and in each case the patient
presented at nosis might able screenin with nephrot. of the kidn puterized to prove our sc ture.
1
age at which the diag- ought. The most valu- intraveno is urography :o detect displacement ography and com- will undoubtedly im- ly diagnosis in the fu-
Surgery re and aggressi for metasta. 1
mainstay of treatment s recommended even is forms of chemo- therapeutic : : | deep x-ray treatment have been us was hoped : .
: it demonstrable effect. It DD (mitotane) might exercise a spinta a :therapeutic effect, but reports have! !!! it prolongs tl
vincing evidence that atients with adrenocor- tical carcino tt ; patient enjoyed no noticeable bes ofit from: its use.
The progn. sis for patients with this tumor remains poor. thy pho rity dying within a year of diagnosis. ” appear that the only benefit that we can offer hese patients is perhaps earlier diagnosis, and his u quires a heightened awareness of the condition.
Meath Hospital Dublin 8, Ireland (DR. SMITH)
Relances
1. Lewinsky B! Chi por Jy symington T, and Neville, AM: The clinical and p hol noci, pat res of ‘non-hormonal’ adenocor- tical tumors. Re: + . : 21 . 1 ;; and review of the literature, Cancer 33: 778 (1!| 4:
2. Hutter AM, Hadice DE A renal cortical carcinoma - clin- ical features of 138 patienti Aro. J. Med. 41: 572 (1966).
3. Anderson EF Nin-fiction ag tumors of the adrenal gland, Urol. Clin. North .m. 4: 253 | 1917).
4. Hajjar RA, Eckes FC. ; d Samaan NA: Adrenal cortical carcinoma, Cance: 35: 549 . 1975
5. Hoffman DI. and Mattox ”R: Treatment of adrenocortical carcinoma with . P. DD:D. Med. Clin. North Am. 56: 999 (1972).