Chance Diagnosis of Low Stage Non-metastasized Adrenal Cortical Carcinoma in a Young Woman with Retroperitoneal Hemorrhage*
Rossana Bussani1, Debora Camilot1, Carlo Trombetta2, Furio Silvestri1
1Department of Pathological Anatomy, University of Trieste, Trieste, Italy 2 Department of Urology, University of Trieste, Trieste, Italy
Summary
Adrenal cortical carcinoma (ACC), a rare and highly malignant neoplasm of the cortical tract of the adrenal gland, is usually diagnosed at an advanced stage of de- velopment and often when metastatic spread already has begun. We report a very rare case of low-stage, non- metastasized ACC, the first clinical appearance of which was a large retroperitoneal hemorrhage caused by the rupture of the neoplastic mass. To the best of our knowl- edge, this is the third reported case of ACC rupture.
Key words: Adrenal cortical carcinoma - Pathology - Retroperitoneal hemorrhage
Introduction
Adrenal cortical carcinoma (ACC) is a rare malignant neoplasm arising from adrenal cortical cells. The diag- nostic criteria of malignancy of an adrenal cortical neo- plasm are somewhat ambiguous, since adenomas also may have cytological abnormalities. A bimodal peak in age incidence has been reported in the first and fifth decades, with a predilection for female patients [5]. The
well-protected deep retroperitoneal location of the adrenal glands together with the fact that, in adults, ACC is not normally accompanied by a neuroendrocrine syn- drome, lead to a late clinical diagnosis, sometimes when distant metastases have occurred, and often when there is a mass effect and/or abdominal pain [1]. For these reasons, the literature includes only a few reports on ma- lignant cortical tumors at low-medium stage.
We report a case of a ACC discovered by chance dur- ing explorative laparoscopy in a young woman with acute abdomen. To the best of our knowledge, this is only the third such case described in the literature [4, 7].
Case Report
A 39-year-old woman, with an unremarkable medical record and mother of two young children, had been ex- periencing slight pain in the lumbar region for some days. The patient attributed this symptom to the physical exertions of looking after the children. One evening, she was struck by an acute pain at the left flank, and shortly afterwards, she suffered from symptoms of shock. She was immediately taken to hospital, where computerized
* This study was supported by a grant from the Ministry of In- struction and Scientific Research (MURST-ex60%-2000).
Address for correspondence: Rossana Bussani, Department of Pathological Anatomy, c/o Ospedale Maggiore, Via Pietà, n. 1, 34125 Trieste, Italy.
Fax: ++39-40-638527.
E-mail: bussani@univ.trieste.it
tomography revealed a large hematoma in the retroperi- toneal space. Surgical abdominal exploration showed that the hematoma, arisen from the left adrenal gland, extended from the left hemidiaphragmatic space to the left pararenal space and the psoas muscle. Left adrenalectomy was then performed. Histological exami- nation of the specimen revealed an adrenal cortical car- cinoma. Postoperative clinical evaluation did not reveal any signs of endocrine dysfunction. Control total body computerized tomography scan and bone scintigraphy were completely negative for metastatic lesions. Chemotherapy with Mitotane was started as an addition- al support to surgery. There was no recurrence of the tumor at follow-up three months postoperatively, and, at the time of writing this report, the patient is well.
Materials and Methods
The resected specimen was fixed in 10% buffered for- malin and processed for traditional histology. Immuno- histochemistry was performed on selected paraffin-em- bedded sections using an autoimmunostainer (Ventana Medical Systems, DiaPath s.r.l., Bergamo, Italy) after heat-induced antigen retrieval using the pressure-cook- ing method.
Results
Pathological findings
Grossly, the surgical specimen measured 13 × 9.2 × 3 cm, weighed 160 grams, and was characterized by a highly hemorrhagic fibroadipose tissue within which a pink- brownish, soft, lobulated, and extensively necrotic neo- plastic tissue was evident. It was not possible to accu- rately determine the extent of the neoplastic area, as the tumor had been extensively fragmented during surgery and was included in the regional soft tissues.
Microscopically, the tumor was composed of irregu- lar pleomorphic cells with predominantly compact, eosinophilic cytoplasm (Fig. 1). A marked degree of nu- clear hyperchromasia, with considerable pleomorphism and hyperlobated or multinucleated aspects, was evident (Fig. 2). The neoplastic cells were arranged in an irregu- lar trabecular growth pattern, with anastomizing cords of cells, sometimes separated by thin sinusoids. Mitotic figures, often atypical, were very frequent, with a mitot- ic index of 12 (counted in 20 consecutive high power fields; × 100 magnifications). The Mib-1 index (deter- mined by counting 1000 tumor cells in the fields show- ing the highest number of positive nuclei) was 70% (Fig. 3). Broad areas of necrosis were evident, as were occasional irregular fibrous bands. Owing to tissue frag- mentation, it was not possible to assess the extent of any invasion of the tumor pseudocapsule.
1
2
3
Immunohistochemistry showed strong positive label- ing of neoplastic cells with vimentin and synaptophysin, while tumor cells did not express epithelial markers (AE1/AE3, epithelial membrane antigen), S100 protein, and chromogranin.
| Reference, year | Patient | Type of tumor presentation | Biological evolution |
|---|---|---|---|
| Kardar AH et al. | Man, | 2-month history of weight loss and fever. | Stage 2 tumor. |
| 2001 | 65 years old | Retroperitoneal hematoma as complication of a fine needle biopsy. | Chemotherapy. Death of tumor 3 months after adrenalectomy. |
| O'Kane HF et al. | Man, | Acute severe abdominal pain; shock. | Stage 1 tumor. |
| 2002 | 52 years old | Spontaneous rupture of the adrenal tumor. | Chemotherapy. Patient alive and well. |
| Bussani R et al. | Female, | Acute severe abdominal pain; shock. | Stage 1 tumor. |
| 2003 | 39 years old | Spontaneous rupture of the adrenal tumor. | Chemotherapy. Patient alive and well. |
Morphohistopathological and immunohistochemical findings were those of a malignant adrenal cortical car- cinoma. There was no tumor extending into the sur- rounding soft tissues.
Discussion
Histological diagnosis of ACC may be difficult for small tumors that have not yet metastasized or invaded adja- cent organs. Tang and Gray demonstrated that the differ- ential diagnosis between adrenal cortical adenoma and adrenal cortical carcinoma has to be made on the basis of a combination of facts, the main ones being size, weight, and microscopic appearance [8]. Hough et al. devised a weighted index based on various parameters, such as diffuse growth pattern, presence of fibrous bands, tumor cells necrosis, capsular invasion, mitotic index, and nuclear pleomorphism [3]. In our case, al- though the precise dimension and weight of the neo- plasm could not be determined, the cytological features, the extent of necrosis, and the other mitotic and prolifer- ative indices leave no question of doubt regarding the malignancy of the lesion.
The notable peculiarity of this case lies not so much in the rarity of the ACC but in the way the tumor re- vealed its presence: a hemoperitoneum caused by the spontaneous rupture of the neoplasm. To date, sponta- neous retroperitoneal hemorrhage has been reported as the prevalent modality of presentation for other types of adrenal tumors, such as metastases, adrenal cortical ade- noma, myelolipoma, and pheochromocytoma [6]. It is quite plausible that the physical exertions caused by the patient’s routine parenting duties promoted the rupture of the tumor along areas of necrosis. This event permit- ted the diagnosis of the neoplasm at a relatively low de-
velopmental stage (pathological stage 1, N0, M0), while, in general, most patients with ACC have ad- vanced disease at the time of diagnosis [1, 2].
Table 1 gives a brief summary of the other two report- ed cases of retroperitoneal bleeding originating from adrenal cortical primary carcinoma. It is very interesting to note that only one patient had a spontaneous rupture of a low stage tumor.
References
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5. Lack EE (1995) Adrenal cortical carcinoma. In: Armed Forces Institute of Pathology (Eds) Tumors of the adrenal gland and extra-adrenal paraganglia. Atlas of Tumor Pathology, 3rd series, fascicle 19, pp 123-152. Washington, DC
6. Machuca Santa Cruz J, Julve Villalta E, Galacho Bech A, et al. (1999) Spontaneous retroperitoneal hematoma: our ex- perience. Actas Urol Esp 23: 43-50
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Accepted in revised version: October 6, 2003