Salivary gland tissues and derived primary and metastatic neoplasms: unusual pitfalls in the work-up of sellar lesions. A systematic review.

PURPOSE: Salivary gland (SG) tissue and derived neoplasms may occur in the sellar region. As the current literature is mostly limited to case reports, the puzzling case of an inflammatory SG removed by transsphenoidal surgery (TS) and mimicking a prolactinoma prompted us to perform the first systematic review of these unusual conditions. METHODS: A systematic literature search was conducted according to the PRISMA guidelines. Forty-four individual cases-non-neoplastic enlarged salivary glands (NNESG, n = 15), primary benign (n = 7) and malignant (n = 8) ectopic salivary tumours (ST) and sellar metastasis from eutopic primary ST (n = 14)-were suitable for the analysis of clinical, radiological and pathological characteristics. Therapeutic outcome was reviewed as a secondary endpoint. RESULTS: All cases were diagnosed after surgery. NNESG commonly affected young and/or female patients, typically leading to headaches and hyperprolactinemia and originating close to the neurohypophysis. Submucosal SG should be excluded before concluding to an intrasellar NNESG after TS. No gender or age predominance was found for primary ectopic ST, which present as large tumors, with histological phenotypes similar to common ST. Hypopituitarism and diabetes insipidus were more frequent in ST than in NNESG. NNESG and benign ectopic ST rarely recur. Malignant ectopic ST should be distinguished from secondary localizations of eutopic ST reaching the sella by contiguity or metastatic spread; both share a frequent unfavorable outcome. CONCLUSION: Sellar neoplasms derived from SG are rare but misleading conditions and pituitary dysfunction is likely to be more common than currently reported. Appropriate pathological evaluation and multidisciplinary approach are required.

Successful treatment of leptomeningeally metastasised pituitary carcinoma with temozolomide.

A 69-year-old man presented with leptomeningeally metastasised pituitary carcinoma, rapidly progressing despite previous treatment with resection, radiotherapy and cabergoline. The patient received temozolomide chemotherapy, resulting in a complete clinical, radiological and biochemical response after 14 cycles, which has been maintained since then. This case lends further support to the role of temozolomide in refractory pituitary tumours.

Colorectal cancer manifesting with metastasis to prolactinoma: report of a case involving symptoms mimicking pituitary apoplexy.

Pituitary metastasis is an uncommon first presentation of systemic malignancy. The most common presenting symptom of pituitary metastasis is diabetes insipidus reflecting involvement of the stalk and/or posterior pituitary. We herein present a unique case of the coexistence of both a functioning pituitary adenoma (prolactinoma) and pituitary metastasis of advanced colorectal cancer with pituitary apoplexy as the first manifestation of underlying malignancy. The present case emphasizes the need to consider pituitary metastasis as a differential diagnosis in patients presenting with pituitary lesions and be aware that tumor-to-tumor metastasis can occur unexpectedly in those with pituitary metastases.

Pituitary carcinoma with endolymphatic sac metastasis.

Pituitary carcinoma is characterized by the presence of a metastatic lesion(s) in a location non-contiguous with the original pituitary tumor. The mechanism(s) of malignant transformation are not known. A 15 year-old male was diagnosed in 1982 with a pituitary macroadenoma and acromegaly (random GH 67 ng/ml and no suppression by oral glucose). His prolactin was normal between 18 and 23 ng/ml. Transcranial resection in July 1983 was followed by radiation therapy. The tumor was immunopositive for GH and prolactin. The proliferation MIB-1 index was 0-1%. With aqueous Octreotide 100 mcg 4× daily both GH and IGF-1 became normal. The patient was lost to follow-up and was treated by his local physician. In 2001, his IGF-1 level was 1271 ng/ml, and his random GH was 1.8-2.4 ng/ml by ILMA despite progressive increase in the dose of Sandostatin LAR to 140 mg/month in divided doses. Prolactin remained normal or minimally increased between 15 and 25 ng/ml. In 2009 he was diagnosed with the tumor in the location of left endolymphatic sac. Histological examination showed low grade pituitary carcinoma strongly immunopositive for prolactin but negative for GH. MIB-1 antibody labeled 0-5% cells. In 2012 endoscopic resection of the pituitary tumor remnant was attempted. Immunohistochemical stains were strongly immunopositive for both prolactin and GH, similar to his original pituitary tumor. The MIB-1 proliferation index was low from 0 to 1%. To our knowledge this is the first case of pituitary carcinoma in the endolymphatic sac region. The dichotomy between the cell population of the pituitary lesion (GH/prolactin producing) and the metastasis (purely prolactin-producing) may suggest that the metastatic pituitary lesion derived from a clone distinct from the original one.

Pituitary carcinoma with fourth ventricle metastasis: treatment by excision and Gamma-knife radiosurgery.

Pituitary carcinomas, which are rare, generally present with craniospinal and systemic metastases. Although several treatments exist, the prognoses of patients with pituitary carcinomas are extremely poor to date. In this report, the authors describe the case of a 23-year-old male who had undergone trans-sphenoidal surgery and radiotherapy for an invasive prolactinoma. Seven years later, he presented with a new 4th ventricle metastasis from the pituitary lesion, and it was diagnosed with a pituitary carcinoma. He underwent resection and Gamma-knife radiosurgery (GKRS). The tumor has been well controlled for over 3 years. To our knowledge, there have been no reports of the effects of GKRS in patients with pituitary carcinomas. GKRS might have considerable effects in the treatment of pituitary carcinomas.

Malignant prolactinoma with craniospinal metastasis in a 12-year-old boy.

The authors report the clinical features of and imaging studies on a rare case of pediatric malignant prolactinoma. A 12-year-old boy presented with ataxia, blurred vision, and consciousness disturbance. He had received transcranial surgery and adjuvant radiotherapy. However, the tumor regrew with craniospinal metastasis 16 months after the operation. The relevant literature was reviewed regarding the clinical presentation, pathogenesis, treatment approaches, and prognosis of malignant prolactinoma.

Pituitary carcinoma with mandibular metastasis: a case report.

Pituitary carcinomas are rare primary adenohypophyseal tumors with cerebrospinal or extracranial metastasis. The present case, the first report of the disease in Korea, involved a 36-yr-old woman who presented with a 3-week history of headache. Brain magnetic resonance imaging revealed a 2.5-cm sellar and suprasellar mass showing heterogeneous enhancement with suspicious invasion of both cavernous sinuses. The patient underwent gross-total resection. The tumor cells were composed of polygonal cells singly or in variable-sized nests. The nuclei were large and round with prominent nucleoli. The cytoplasms was acidophilic and granular. Marked pleomorphism and frequent mitoses (3 per 10 HPFs) were found. By immunohistochemistry, tumor cells were strongly positive for prolactin, but negative for ACTH and GH. Additional immunostainings for cytokeratin, vimentin, and glial fibrillary acidic protein (GFAP) were negative. After the surgery, the patient received radiotherapy because of the atypical histologic features. The prolactin level fell from 123.17 ng/mL to 5.17 ng/mL after surgery. Nine months after the initial diagnosis, the patient died from mandibular metastasis associated with the pituitary carcinoma.

Long-term response of pituitary carcinoma to temozolomide. Report of two cases.

Pituitary carcinoma is a rare tumor characterized by poor responsiveness to therapy, leading to early death. Reported responses to standard chemotherapy have only been anecdotal, with no single agent or combination demonstrating consistent efficacy in the treatment of patients with this disease. The authors report rare examples of a persistent response to cytotoxic chemotherapy in two patients with pituitary carcinoma. One patient was a 38-year-old man with visual field loss caused by a luteinizing hormone-secreting pituitary carcinoma that had recurred despite multiple surgeries and radiation therapy. Intradural metastases to the spine that had failed to respond to radiation therapy were pathologically confirmed. The second patient was a 26-year-old man with hyperprolactinemia from a prolactin-secreting pituitary tumor. Spine magnetic resonance images obtained to search for causes of neck pain showed a vertebral tumor, which was later confirmed through pathological analysis to be a metastatic pituitary carcinoma. His disease progressed despite radiation therapy, high-dose bromocriptine, and chemotherapy. Both patients were treated monthly with temozolomide, which was administered orally on the first 5 days of a 28-day cycle. The patient in the first case underwent all 12 treatment cycles without serious side effects, and his visual field deficits improved. The patient in the second case had undergone only 10 cycles when the drug was stopped because of his severe fatigue. Nonetheless, his pain disappeared and his serum prolactin concentration decreased. Both patients continue to have partial responses and have been employed full-time for more than 1 year after discontinuing temozolomide therapy. These two examples demonstrate that temozolomide may be effective in treating pituitary carcinomas and thus should be considered in the treatment algorithm for these difficult cases.

Metastatic prolactinoma: case report with immunohistochemical assessment for p53 and Ki-67 antigens.

Pituitary carcinomas are rare neoplasms characterized by craniospinal and/or systemic metastases originated from the pituitary. Their histopathology is frequently indistinguishable from that of benign adenomas. The development of markers that better reflect their behavior is desirable. We present the case of a 47 year-old man with a prolactin-secreting macroadenoma who was submitted to surgeries, cranial radiation therapy, and bromocriptine treatment, but evolved to a fatal outcome after the disclosure of intracranial metastases. Tumor samples underwent p53 and Ki-67 immunohistochemical assessment. p53 was absent in all samples, a rare finding among pituitary carcinomas. Ki-67 proliferative index was 2.80% in the original tumor, 4.40% in the relapse, and 4.45% in the metastasis. The figure in the relapse is higher than the expected for a noninvasive adenoma. In conclusion, p53 staining is not positive in all pituitary carcinomas. A high Ki-67 proliferative index in a pituitary adenoma might indicate a more aggressive behavior.

Metastatic prolactinoma: case report with immunohistochemical assessment for p53 and Ki-67 antigens

Pituitary carcinomas are rare neoplasms characterized by craniospinal and/or systemic metastases originated from the pituitary. Their histopathology is frequently indistinguishable from that of benign adenomas. The development of markers that better reflect their behavior is desirable. We present the case of a 47 year-old man with a prolactin-secreting macroadenoma who was submitted to surgeries, cranial radiation therapy, and bromocriptine treatment, but evolved to a fatal outcome after the disclosure of intracranial metastases. Tumor samples underwent p53 and Ki-67 immunohistochemical assessment. p53 was absent in all samples, a rare finding among pituitary carcinomas. Ki-67 proliferative index was 2.80% in the original tumor, 4.40% in the relapse, and 4.45% in the metastasis. The figure in the relapse is higher than the expected for a noninvasive adenoma. In conclusion, p53 staining is not positive in all pituitary carcinomas. A high Ki-67 proliferative index in a pituitary adenoma might indicate a more aggressive behavior.

Carcinomas pituitários são neoplasias raras caracterizadas pela presença de metástases cranio-espinhais e/ou sistêmicas originadas da hipófise. Sua histopatologia é freqüentemente indistinguível daquela dos adenomas benignos. O desenvolvimento de marcadores que melhor reflitam o seu comportamento é desejável. Apresentamos o caso de um homem de 47 anos com um macroadenoma secretor de prolactina que foi submetido a procedimentos cirúrgicos, radioterapia e tratamento com bromocriptina, mas que evoluiu para o óbito após o descobrimento de metástases intracranianas. Amostras do tumor foram submetidas à análise imuno-histoquímica para os antígenos p53 e Ki-67. A coloração para p53 foi negativa em todas as amostras, um achado raro entre os carcinomas pituitários. O índice proliferativo Ki-67 foi 2,80% no tumor original, 4,40% na recidiva e 4,45% na metástase. O valor obtido na recidiva é maior que o esperado para um adenoma não-invasor. Concluindo, a coloração para p53 não é positiva em todos os carcinomas pituitários. Um índice proliferativo Ki-67 alto em um adenoma pituitário poderia indicar um comportamento mais agressivo.

Malignant prolactinoma: is metastasis a must? Clinico-pathologic and immunohistochemical study of a case.

Pituitary carcinomas are rare tumors which have been conventionally defined as primary adenohypophyseal tumors with cerebrospinal or extracranial metastases. According to the current criteria even a highly invasive tumor without metastases is not considered as malignant. A case of pituitary adenoma is reported with an unproven site of metastasis but with rapid increase in prolactin levels (35,000 ng/ml), showing extensive invasion on radiology, and pathological and immunohistochemical studies indicating a highly mitotic variety of tumor. On the basis of this case we want to emphasize that extracranial metastasis is not a must to label a pituitary adenoma as a malignant tumor. Such aggressive behavior of the tumor and clinico-pathological course in itself should be sufficient for the tumor to be labeled as malignant.

A case of prolactin-secreting pituitary carcinoma and its histological findings.

Pituitary carcinomas are very rare. The diagnosis of pituitary carcinoma is defined by evidence of craniospinal and/or systemic metastasis, rather than by histological malignancies. We report a case of prolactin-secreting pituitary macroadenoma invading the cavernous sinuses at the time of initial treatment, which later metastasized to the cerebellum, medulla oblongata, and spinal axis. The patient survived approximately nine years following the initial diagnosis of a pituitary tumor and two years following the diagnosis of metastatic disease. Histological examination of the metastatic cerebellar tumor showed an adenoma with high cellularity and hyperchromasia, but no mitoses.

Malignant prolactinoma with multiple bone and pulmonary metastases. Case report.

Malignant prolactinomas, as with other pituitary carcinomas, are rare tumors. The authors describe a 14-year-old boy who presented with visual loss caused by a pituitary prolactinoma. He underwent transsphenoidal surgery, radiotherapy, and dopamine agonist therapy, but 6 years after the initial diagnosis his pituitary tumor regrew and bone and pulmonary metastases developed. The authors review the literature and discuss the clinical presentation of malignant prolactinomas, their rarity, histological characteristics, distribution of the metastases, different treatment approaches, and their poor prognosis.

Late development of frontal prolactinoma after resection of pituitary tumor.

The unusual case of a patient with a frontal lobe prolactinoma developed 14 years after resection of a histologically benign pituitary adenoma is presented. Sixteen years after resection of this frontal mass, and 30 years after the first intervention, the patient is symptom-free and without evidence of new intracranial tumors. The possibility that frontal tumor resulted as the late proliferation of microscopic tumor seeding that took place in the course of the first surgery, is suggested. Although this case can be considered as a pituitary carcinoma, the clinical course supports that tumor seeding from pituitary tumors not necessarily indicates a poor prognosis.

Orbital invasion with prolactinoma: a clinical review of four patients.

PURPOSE: To present four patients with invasive prolactin-secreting pituitary adenomas extending in the orbit. METHODS: Retrospective, noncomparative case series. RESULTS: In all cases, the tumor was a large, invasive prolactin-secreting adenoma. In three cases, significant permanent vision loss occurred and severe disfigurement resulted; two of these patients died of tumor-related complications. In one case, the tumor responded well to medical treatment, and the orbital symptoms improved significantly. CONCLUSION: Although it is rare for a pituitary adenoma to invade the orbit, devastating consequences to the integrity of the globe and ocular adnexa may result. Therefore, early recognition and proper treatment of orbital pituitary tumors are of utmost importance to minimize ocular and orbital damage.

[Malignant prolactinoma with intra- and extracranial metastasis: clinico-radiologic study]. / Prolactinoma maligno con metástasis intra y extracraneales: estudio clínico-radiológico.

Malignant prolactinomas are very rare pituitary neoplasms which can be identified not from the hystopathologic nor neuroimaging aspects but only retrospectively from the presence of distant metastases. A 32-year-old male patient was diagnosed of a pituitary prolactinoma because of bitemporal hemianopsia on the basis of cranial MRI aspect and raised blood prolactin level. Visual signs improved under bromocriptine treatment but after surgical and X-ray therapies patient developed paralysis of V and XII left cranial nerves and suffered from medulocerebelous angle, vertebrae, spinal epidural space, lung, liver, suprarenal and femoral metastases. Patient died 3 years after the diagnosis time. Prolactin levels raised 2000 ng/ml. This is the first case of malignant prolactinoma described in the spanish literature and the more large one in number of metastatic localizations between the malignant prolactinomas from the literature. These kind of neoplasms can be partially ameliorated under X-ray and bromocriptine treatment but there is not, by the moment, a curative chemotherapy.

Prolactinoma maligno con metástasis intra y extracraneales: estudio clínico-radiológico / Malignant prolactinoma with intra- and extracranial metastasis: clinico-radiologic study

Los prolactinomas malignos, tumores extremadamente raros, no pueden diagnosticarse en base a la histología ni a existencia de invasión local en los estudios de neuroimagen, sino a posteriori, al objetivarse metástasis a distancia. Un varón de 32 años fue diagnosticado (RM craneal y determinaciones hormonales) de tumor hipofisario productor de prolactina, a raíz de presentar un síndrome de compresión del quiasma óptico. Respondió inicialmente a bromocriptina, pero posteriormente las cifras de prolactina llegaron a alcanzar los 2000 ng/ml. Después de ser intervenido e irradiado, desarrolló afección unilateral de V y XII pares y metastatizó en ángulo bulbocerebeloso, diversas vértebras, espacio epidural espinal, pulmón, hígado, suprarrenales y fémur. Falleció a los 3 años del inicio de los síntomas. Es el primer caso de prolactinoma maligno de la literatura española y el de mayor número de localizaciones metastásicas, entre los publicados. Estos tumores pueden responder parcialmente a radioterapia y agonistas dopaminérgicos; no se conoce, por el momento, un tratamiento quimioterápico eficaz (AU)

Malignant prolactinoma: case report and review of the literature.

BACKGROUND: Malignant prolactinomas are rare events. To date, only 14 patients with metastases in- or outside the central nervous system have been reported. CASE DESCRIPTION: We present a patient who developed a metastasis to the cauda equina, which is the first case documented with MRI. A giant prolactinoma in this 51-year-old man was partially removed by a transcranial approach. After radiotherapy and treatment with bromocriptine, the patient had a remission for 3 years. Thereafter, a sacral intraspinal tumor was diagnosed. Because of increasing prolactin levels not responding to bromocriptine and a radiologically suspected intrasellar tumor, we operated transsphenoidally first and found only fibrous tissue. We performed a sacral laminectomy and almost totally removed an intradural tumor. Histopathology and immunohistochemistry confirmed the diagnosis of a prolactinoma metastasis. The patient received radiotherapy and bromocriptine and has no evidence of recurrent tumor or metastases after a follow-up of 38 months, thus being the second reported patient with long-term remission of the disease. DISCUSSION: We review the literature on this topic and try to establish common features of the course of this rare malignant disease and the efficacy of therapy in the cases reported hitherto.