Pituitary metastasis in lung adenocarcinoma

Dear Editor, Amongst the mass lesions affecting the pituitary gland, surgical resections are performed for pituitary adenomas that form bulk of the sellar and supra-sellar lesions. On the other hand, pituitary metastasis (PM), first described in 1857 with pituitary invasion by melanoma, are encountered to an extent of 28% at postmortem examinations, especially with cancerous dissemination1 but are seen in 1%–3.6% of the surgical excisions.2 We report PM, noted as an incidental medico-legal autopsy finding in a patient with pulmonary mucinous adenocarcinoma with widespread dissemination. The body of a 40-year-old pre-menopausal woman was referred to our tertiary care centre for a medico-legal autopsy from a nearby cancer centre, where she had a sudden collapse in the outpatient department. The patient had a 3-month history of pain in the abdomen and lower back. A computed tomographic scan of the abdomen in the cancer centre had shown multiple osteolytic lesions in the pelvic bones, thoracolumbar vertebrae and right 11th rib with a bulky left adrenal gland and focal hepatic nodularity. At autopsy, the source of widespread metastases had been a large (3.8 cm × 3.5 cm × 2.9 cm) tumour mass in the apical segment of the upper lobe of the left lung with associated pleural puckering Figure 1a, bilateral scattered intra-parenchymal miliary metastases and lymphangitic carcinomatosis. On histomorphology, the tumour was a mucinous adenocarcinoma with acinar corresponding to the central grey-white areas as shown in Figure 1a and peripheral lepedic corresponding to the glistening pale grey parenchyma, as shown in Figure 1a patterns; focal clusters of signet ring cells were also present. In addition, there were large mucin-filled cystic spaces lined by mucigenic columnar cells with micro-papillae Figure 1b. The pituitary gland was enlarged (8.2 g, reference values of 0.5–0.9 g) and very firm to feel with a pale yellow cut surface and few congested areas Figure 1c; some of these areas showed normal glandular architecture. The rest of the gland was occupied by metastatic adenocarcinoma in a predominant acinar pattern Figure 1d. The brain parenchyma revealed focal meningeal carcinomatosis and mucinous metastases in the cerebrum and cerebellum; similar tumour morphology was seen in all other affected organs.Figure 1: (a) Large tumour sub-pleural mass with associated pleural puckering (black arrow). The central part of the tumour was opaque, pale yellow to grey-white with small cystic areas with a peripheral rim of pale grey-glistening consolidated parenchyma (white arrow); (b) Tumour composed of mucin-secreting glands with larger cystic spaces-containing papillary structures and mucin (H and E, ×100); (c) Enlarged bisected pituitary replaced by pale-yellow tumour; (d) Metastatic adenocarcinoma showing mainly acinar pattern (H and E, ×250)Extensive metastasis to the pituitary gland was noted as an incidental finding in a young woman with disseminated mucinous adenocarcinoma. Such a metastatic disease occurs in conjunction with brain parenchymal metastases, accounting for 0.4%–1% of intracranial secondary tumours.2 The patients are aged between 60 and 70 years with advanced cancer, particularly involving the bones,2 as seen in this case, but our patient was young. Occasionally, the gland may be the sole site and may also indicate the presence of an occult malignant neoplasm.2,3 Moreover, the pituitary gland can also demonstrate tumour-to-tumour metastasis.4 Mechanisms for spread include hematogenous route (being the most common), meningeal spread via suprasellar cistern or even a direct invasion from adjacent bony structures harbouring metastases.1-3 The vast majority of patients are asymptomatic as pituitary involvement may be masked by manifestations of the primary tumour or its systemic metastases. Only 6.8% of the patients are symptomatic, often presenting with non-specific symptoms such as headache, visual field defects and cranial nerve palsies.1-3,5 The neurohypophysis, due to its small size and direct arterial supply, is involved in three quarters of the cases, which explains central diabetes insipidus as a key feature, seen to the tune of 50% in symptomatic metastasis (unlike other sellar tumours).5 The adenohypophysis, perfused by the hypophyseal portal system, is affected in about 15% of the cases, and 25% of patients present with anterior pituitary deficiency with reduction of one or more adenohypophyseal hormones; panhypopituitarism is uncommon.1-3,5 No such preferential deposition could be seen in the case presented, as there was complete replacement of the gland, and she apparently did not have any feature to suggest pituitary metastasis. Although all malignant neoplasms are capable of producing PM, more than half of the cases originate from the breast (39.7%) or lungs (23.7%).6 Amongst the lung cancers, the most common tumour implicated is small cell carcinoma.7 The pituitary is a rare site of metastases for lung adenocarcinomas, which commonly metastasise to the liver, adrenal glands and bones.8 There has been a recent review of 15 such patients8 affecting mainly women (10 patients), with a mean age of 57.7 years; only 1 patient did not have symptoms related to PM. In this case, the clinical presentation was related to bone metastases, and respiratory symptoms had not been documented. On histology, there are three patterns of metastases-focal or multifocal cell clusters, diffuse infiltration with partial/complete obliteration of the architecture or acinar filling (‘parasitisation’);9 almost complete obliteration was seen in our case. Although PM portends a poor prognosis, a multidisciplinary approach is nevertheless advocated, depending on the primary site of the cancer, associated non-pituitary metastases and other co-existing morbid conditions. Given the innovations in radio-imaging and improved survival of cancer patients, presence and varied presentations of PMs should not be overlooked. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.