We report a case of PitNET with a history of colorectal and bladder cancers and a relatively rapid progression of neurological symptoms, in whom early surgical intervention revealed metastasis of a malignant neoplasm within the PitNET. Histopathological evaluation revealed the presence of a new lung adenocarcinoma.
It is estimated that PitNETs account for nearly 80% of the tumors of the sella turcica, and although the majority of neoplasms in the sella turcica are PitNETs, reports of collision tumors, in which a malignant neoplasm has metastasized to a PitNET, are extremely rare, with only 33 cases reported so far [2–29] (Table 1).
Including the present case, the average age of the previously reported patients was 66 years (44–87 years), with 16 men and 17 women. The breakdown of the primary malignant neoplasms was as follows: malignant neoplasms of the lung and trachea (n = 7), breast (n = 7), digestive organs (n = 5), kidney and urinary organs (n = 5), neuroendocrine tumors (n = 3), malignant melanoma (n = 2), and unknown (n = 4). The breakdown of primary malignant neoplasms was similar to that of pituitary metastases  (Fig. 4). The breakdown of recipient PitNETs was as follows: NF PitNET (n = 22), prolactinoma (n = 6), acromegaly (n = 4), and Cushing's disease (n = 1). This is similar to the incidence of PitNETs themselves, suggesting that there is no affinity between specific PitNETs and malignant neoplasms, and that they metastasize by the same mechanism as pituitary metastases of malignant neoplasms (Fig. 5).
In other words, in cases of pituitary metastases of malignant neoplasms, the malignant neoplasm tends to metastasize to the posterior lobe of the pituitary gland via the arterial blood flow of the neurohypophysis in the same way that the malignant neoplasm tends to metastasize into the tumor of the sella turcica via the abundant arterial blood flow that nourishes the pituitary gland, including branches of the capsular artery, inferior hypophysial artery, and superior hypophysial artery of the internal carotid artery .
In addition, previous reports have supported the hypothesis that PitNETs activate trophic vasculature and increase blood flow to the sella turcica via such trophic vessels . Other possible mechanisms include direct invasion from adjacent bony structures or the meninges, or through the cerebrospinal fluid surrounding the sella turcica . Of the patients with malignant neoplasm metastasized within a PitNET, only 60% (n = 20/33) had a known history of malignant neoplasm prior to definitive diagnosis, and only 15% (n = 5/33) had other intracranial metastases preoperatively.
As in previous reports, the present case had a history of malignant neoplasms of the bladder and colon but no other intracranial metastases. In the present case, there were no respiratory symptoms, and histopathological examination revealed the presence of adenocarcinoma of the lung within the PitNET, indicating a new malignant neoplasm of the lung, and thus, triple cancer.
As stated in previous reports, it is difficult to distinguish between a PitNET alone and a malignant neoplasm metastasizing within a PitNET preoperatively, based only on clinical and imaging findings. In many cases, metastatic lesions are too small to cause any clinical or imaging changes. If symptoms occur, they are often the same as those of PitNET alone and may include poor visual function due to optic chiasm drainage, headache, hypopituitarism, and slight hyperprolactinemia.
Considering the appearance of external ophthalmoplegia, it is more natural to consider PitNETs associated with pituitary apoplexy rather than collision tumors in the differential diagnosis. This is because 27% (n = 9/33) of patients with metastases of malignant neoplasms within PitNETs had external ophthalmoplegia, whereas 58.8% (n = 10/17) of patients with PitNETs alone had external ophthalmoplegia in the presence of pituitary apoplexy [32, 33].
Imaging evaluations, such as CT and MRI, are helpful in assessing the localization and extension of tumors of the sella turcica; however, it is still difficult to distinguish between a PitNET alone and a malignant neoplasm metastasizing within a PitNET.
However, as is the case with metastases of malignant neoplasms to the parasellar region, metastatic disease should be considered when there is invasive destruction of bony structures such as the sella turcica, anterior and posterior floor processes, dorsum sellae, and plateau; when there is rapid growth of the lesion on routine imaging evaluation; or when other intracranial lesions suggest metastases .
As a result, histopathological examination is essential for a definitive diagnosis, and it is important that the tumor is removed as much as possible. The entire removed tumor specimen is immunostained and histologically assessed to ensure that no malignant lesions are missed.
The prognosis of patients with metastases of malignant neoplasms within PitNETs is generally poor, as the malignancy is often already intracranially and systemically disseminated.
The literature indicates that 56% of patients have systemic metastases, 19% have intracranial metastases, and the median survival is reported to be 4 months [19, 25, 26] .
Recently, advances in diagnostic imaging have made early detection possible, and advances in chemotherapy, such as molecular-targeted drugs, have led to reports of good prognosis in cases of metastases of malignant neoplasms within PitNETs .
In the present case, with appropriate histopathological evaluation, chemotherapy with molecular-targeted agents, and additional stereotactic radiotherapy, both lung and sella turcica lesions progressed well with good tumor control and a relatively good outcome.
Endoscopic endonasal transsphenoidal surgery, which is relatively minimally invasive, may be an option not only for immediate decompression of the tumor and improvement of abnormal hormone secretion but also for diagnosis. Hence, the collection of a tumor specimen and the correct diagnosis of malignant neoplasm metastasizing to a lesion in the sella turcica, as in the present case, will allow to formulate a detailed treatment plan. Further, patients with advanced-stage malignant neoplasms can be spared invasive tests and unnecessary aggressive treatments.