Case Report Concomitant renal cell carcinoma with pituitary adenoma
J. Weber1, A. M. Gassel2, A. Hoch1, and A. Spring1
1 Department of Neurosurgery, Leopoldina Hospital, Schweinfurt, Germany
2 Institute of Pathology, University of Würzburg, Germany
Published online March 3, 2003
C Springer-Verlag 2003
Summary
Renal cell carcinoma has a complex and variable natural history. We report a case underlining this who presented concomitant renal cell carcinoma metastasis with pituitary and adrenocortical ad- enomas. A 62-year-old woman presented with visual loss. Imaging revealed a large sellar mass with suprasellar extension. Four years before, nephrectomy and adrenalectomy had been performed for a renal cell carcinoma with metastasis in a coexistent adrenocortical adenoma. Faced with progressive visual loss and the questionable pituitary pathology, the patient underwent trans-sphenoidal surgery. Due to profuse tumor bleeding, only a biopsy was possible. In a sec- ond operation, the patient underwent craniotomy with subtotal re- section of the tumor. Histological examination of the specimen revealed a metastasis of the renal cell carcinoma and a pituitary ad- enoma. The case presented here and a review of the reports suggest that there are some differences between the clinical features and outcomes of metastases of renal cell carcinoma and those of pituitary gland metastases from other primary sites.
Keywords: Pituitary adenoma; adrenocortical adenoma; metas- tases; renal cell carcinoma; chiasma compression.
Introduction
The incidence of pituitary involvement in metastatic cancer is between 1% in clinical reports and 69.3% in pathological reviews, and it has been reported mainly in patients with breast or lung cancer [1, 3, 14, 16, 18, 27, 30, 31]. However, the majority of these patients were asymptomatic. When symptoms are present, they tend to be related to posterior pituitary dysfunction, which results in diabetes insipidus [16, 18, 20, 27].
Renal cell carcinoma frequently appears in unusual metastatic sites [25, 28]. We report a case presenting renal cell carcinoma metastasis concomitant with pi-
tuitary adenoma. Four years prior to admission, the patient was operated on for a renal cell carcinoma with metastasis in a co-existent adrenocortical adenoma. Its clinical features and outcome differ somewhat from those of metastases from other primary tumors in the pituitary gland.
Case report
A 62-year-old woman presented with a 4-month history of in- creasing bifrontal headache and visual loss. Computed tomography (CT) and magnetic resonance imaging (MRI) revealed a large sellar mass with suprasellar extension (Fig. 1a/b).
Four years previously, the patient had undergone radical neph- rectomy and adrenalectomy due to a renal cell carcinoma with me- tastasis in a co-existent adrenocortical adenoma (Fig. 2a/b). Other metastases were not detected at that time.
Examination on admission disclosed bitemporal hemianopsia and decreased visual activity in the left eye. The serum values of pituitary hormones were within standard ranges. Confronted with relentlessly progressive visual loss and the questionable pituitary pathology, the patient underwent trans-sphenoidal surgery. However, only a biopsy was possible because the surgical procedure was complicated by profuse tumor bleeding. The patient therefore underwent left subfrontal/-pterional craniotomy with subtotal resection of an intra- and suprasellar tumor. Upon exposure of the sphenoid sinus and the sella, no evidence of bone or dural involvement by the tumor was noted.
Histological examination revealed two distinct morphological patterns (Fig. 2c). On the one hand, a tumor of the pituitary gland was found, with nodular masses of medium-sized cells with solid or pseudofollicular growth. These cells tested negatively on immuno- histochemical staining with antibodies for the pituitary hormones corticotropin, somatotropic hormone, and thyrotropin. On the other hand, an adjacent tumor of pleomorphic clear cells with hemor- rhagic necrosis was found. Thus, metastasis of the renal carcinoma in a pituitary adenoma was diagnosed.
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The patient showed no other clinical evidence of metastatic disease from her primary tumor. Because of a change in her mental status coupled with clinical and laboratory evidence of hypopituitarism, therapy with hydrocortisone and thyroid hormone was started post-
operatively. The patient suffered from transient diabetes insipidus, probably because of dysfunction of the hypothalamic nuclei. Her vision worsened with additional reduction of the visual field. She needed complete care and died 8 months later from pneumonia.
| Author | Symptoms and signs | Interval from primary diagnosis | Pathology | Metastases with pituitary adenoma | Treatment | Outcome and survival times |
|---|---|---|---|---|---|---|
| Post et al., 1980 [23] | VD | 0 months | ND | first diagnosis pituitary adenoma than metastasis | T (PR), TS (one year later) | ND |
| Anniko et al., 1981 [2] | H, VD | 9 years | DM | ND | TS (PR or TR?) | CRS, 1 month |
| Buonaguidi et al., 1983 [5] | VD, H | 0 months | SM | ND | T (PR) | PRS, ND |
| James et al., 1984 [12] | VD | 9 years | SM | Yes | R, TS (PR) | CRS, ND |
| Eick et al., 1985 [9] | H | 0 months | SM | ND | TS (PR), R | ND, DM 3 years after surgery |
| Branch et al., 1987 [4] | ND | known primary cancer | ND | ND | TS | ND |
| McCormick et al., 1989 [18] | VD | 12 months after frontal Trepanation | DM 12 months after Trepanation | first diagnosis pituitary adenoma than metastasis | T, R, TS 12 months after T | PRS, 22 months after T |
| Koshiyama et al., 1992 [13] | VD, H, DI | 0 months | DM | ND | T (B), R | ND, no change of the mass intrasellar one |
| Nishio et al., 1992 [22] | VD | 4 years | SM | ND | TS (B), R | year after T (MRI) PRS, no change in size of the tumor 10 months after TS |
| Morita et al., 1998 [20] Present case, 2003 | ND | 5 years 4 years | ND SM | ND Yes | ND TS (B), T (PR) | ND |
| VD | NRS, death 8 months after T (pneumonia) |
B Biopsy; CP complete removal; DI diabetes insipidus; DM disseminated metastasis; H hypopituitarism; ND not described; N/P/C RS no, partial, or complete recovery from initial symptoms; PR partial removal; R radiation; SM solitary metastasis; T subfrontal/pterional trepa- nation; TS trans-sphenoidal surgery; VD visual disturbance.
Discussion
Clinicopathological review
Metastatic lesions involving sellar structures appear mainly in terminal malignancy [3, 7] and are relatively common autopsy findings in cancer patients [1]. Fre- quently, the pituitary tissue appears quite normal at autopsy and only meticulous microscopic examination reveals the tumor [14, 30]. According to autopsy re- ports only 6.8-16% of cases were symptomatic [16, 30]. In general, if metastases to the pituitary were evi- dent, they occurred as multiple metastases. Thus, the symptoms and signs of pituitary insufficiency can be masked. A significant number of patients with primary cancers may have pituitary insufficiency that is not appropriately diagnosed [20].
In the reported cases of renal cell metastasis in the pituitary gland (Table 1), five patients had no prior history of cancer, while previously diagnosed neo- plasms were present in six. In four of eleven cases, the
pituitary gland was the only location of renal cell car- cinoma metastases. These observations are unusual in metastatic lesions involving the pituitary gland [18]. The interval from primary malignancy to pituitary metastasis is in general several years (up to nine) (Table 1).
Renal carcinoma has a complex and variable natu- ral history [25]. The single most important factor af- fecting survival is the presence or absence of metastatic disease. About 25% of patients have metastatic disease at diagnosis. Eighty percent of the patients with meta- static disease at the time of nephrectomy died from the tumor within 24 months of surgery, as opposed to only 10% of those with no demonstrable metastases [29]. This carcinoma tends to cause metastatic lesions that are clinically silent until many years after the pri- mary tumor has been identified, as was the case in our patient.
The posterior lobe, alone or in combination with the anterior lobe, was the site of metastases in 69.3% in a study of 88 cases; only 13.6% involved the anterior
lobe alone [30]. The posterior lobe receives a direct systemic arterial blood supply, which may explain the higher frequency of metastatic tumors there [30]. A clinicopathological review of 88 cases of carcinoma metastatic to the pituitary gland showed no renal cell metastasis [30].
The coincidental presence of pituitary and adreno- cortical adenomas along with metastasis from a renal cell tumor, as in our case, has never been reported be- fore, and renal cell carcinoma metastasizing into an- other tumor has rarely been reported [24]. In addition, the co-existence of a pituitary adenoma and a meta- static pituitary lesion has been reported in three cases [12, 18, 23]. In two of them [18, 23], histological ex- amination confirmed the presence of a pituitary ad- enoma. After a renal carcinoma was found, retrospec- tive review of the preceding histological examination was consistent with metastasis from a renal cell carci- noma. Although our case may only reflect the statisti- cally unlikely occurrence of two relatively uncommon events in the pituitary and adrenal glands, the disrup- tion of the normal vascular system by an adenoma may predispose to infiltration by blood-borne metas- tases [6]. Second, intra-adenomatous renal cell carci- noma metastasis may have been the consequence of acquisitation by renal cells of adhesion molecules spe- cific for endothelial cells within the adenoma [15].
Clinical features and diagnostic aspects
The greater incidence of metastatic lesions in the posterior hypophysis correlates well with the greater frequency of diabetes insipidus than anterior pituitary failure [7, 16, 18, 30]. Anterior pituitary insufficiency due to metastatic neoplasm has rarely been reported [13, 21, 30]. Only about 7-25% of patients harboring pituitary metastases presented with symptoms related to hypopituitarism, while 70% had diabetes insipidus [16]. Visual disturbance was the most common symp- tom in patients with renal cell metastasis to the pitu- itary gland (eight of eleven). This observation is un- usual in metastasis to the pituitary gland. It was reported that 7-33% of cases with pituitary metastasis showed symptoms due to optic nerve palsy [16, 18, 20].
The clinical manifestations of pituitary metastasis and adenoma differ. Metastases cause diabetes in- sipidus and less commonly, oculomotor palsies. These symptoms occur in fewer than 2% of patients with pi- tuitary adenoma [16]. Visual loss and anterior pitu-
itary insufficiency, characteristic of pituitary adenoma, are infrequent initial symptoms of sellar metastasis [16].
The present case showed only bitemporal hemi- anopsia, and we cannot be certain whether the visual field defect was caused by the metastasis or the co- existent adenoma. On pathological evaluation, the metastatic lesions in three of the reported cases were found to be co-existent with a pituitary adenoma. These observations could explain the typical visual disturbance in patients with renal cell metastasis to the pituitary gland. Table 1 summarizes the symptoms, pathology, treatment, and outcomes of reported cases of metastatic renal call carcinoma to the pituitary gland.
Radiological studies may not help in the differential diagnosis of an intrasellar mass [8, 17]. Evidence of juxtasellar bony and soft tissue involvement is not di- agnostic of intrasellar metastasis, because pituitary adenoma may be invasive [8], and intrasellar adenoma and juxtasellar metastasis may co-exist (as in the pres- ent case).
Treatment and prognosis
In two studies, approximately 1% of pituitary le- sions treated by trans-sphenoidal surgery were meta- static tumors [4, 19]. In cancer patients, the distinction between pituitary metastasis and adenoma may affect the choice of treatment. The association of a sellar tu- mor and progressive visual loss (without diabetes in- sipidus) suggests pituitary adenoma [16] or, rarely, renal cell metastasis. Surgery may be appropriate in cancer patients with visual loss. In those with diabetes insipidus, subsequent visual impairmet may result from malignant infiltration of the optic nerves and chiasm rather than from compression of these struc- tures by an extrinsic tumor [16]; therefore, we favor conservative therapy (radiation and drugs). Patients demonstrating widespread neoplastic disease with pituitary metastasis producing diabetes insipidus or anterior pituitary failure are better managed with hormonal replacement [18].
In all reported cases, surgery was complicated by profuse tumor bleeding and, in most, only biopsy or partial removal could be performed (Table 1), includ- ing the present case. One case report presented intra- operative, ultrasonographically guided, direct ethanol injection for a brain metastasis from renal cell carci- noma to reduce vascular flow before initiating of re-
moval [11]. Because of the eloquent area, this proce- dure is risky in pituitary lesions.
Neither hormonetherapy nor chemotherapy has been able to modify the clinical course of metastatic renal cell carcinoma, and the role of radiotherapy is limited to palliation [10, 32]. Recently, interferon al- pha [26] and interleukin-2 were successfully used in advanced renal carcinoma, with some complete and long-lasting response; however, the role of these sub- stances in the adjuvant setting remains to be defined [10]. Complete removal of the malignancy (radical nephrectomy) provides optimum disease control [29]. The role of metastatic surgery is limited to palliation. Adjuvant radiation therapy was given in four of the cases reported.
The present case supports the general consensus that neurosurgical intervention may be of symptomatic benefit, especially against visual loss, and possibly prolong life in some patients with renal cell carcinoma.
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Correspondence: Jochen Weber, M.D., Department of Neuro- surgery, Leopoldina Hospital, Gustav-Adolf-Straße 8, 97422 Schweinfurt, Germany.