Aggressive pituitary lesion with a remarkably high Ki-67

Abstract

SUMMARYThe uncommon aggressive pituitary tumors are named carcinomas when metastases are detected, either in the central nervous system and/or systemically. Some cases are associated with hormonal overproduction, but most are diagnosed because of local symptoms. These neoplasias are generally refractory to current treatments. A 51 year-old woman presented sudden onset of headache, left arm paresis and left facial hypoesthesia. Computed tomography scan and magnetic resonance imaging revealed a pituitary tumor invading the left sphenoidal and cavernous sinuses. Laboratory data excluded hormonal hypersecretion. The patient underwent transsphenoidal surgery and histological findings showed a neoplasia with Ki-67 estimated at 75%. Medical imaging excluded both a primary occult tumor and central nervous system or systemic dissemination. Three weeks postoperatively, neurological condition worsened, with new onset of ataxia, bilateral ptosis, ophthalmoplegia and an increase in the size of the lesion, leading to surgical intervention by craniotomy, followed by only a few sessions of radiotherapy, because of severe disease progression. Patient died nearly 2 months after the initial manifestations. This case illustrates the aggressiveness of some pituitary lesions, the limited efficacy of current treatment modalities such as surgery or radiotherapy and the pitfalls of the current pituitary tumors classification. To our knowledge, this case corresponds to one of the most aggressive pituitary neoplasms reported so far, with a very high Ki-67 index (75%) and short survival SUMÁRIOOs raros tumores pituitários agressivos são chamados carcinomas quando são detectadas metástases, sejam sistêmicas e/ou em sistema nervoso central. Alguns casos estão associados com superprodução de hormônio, mas a maioria é diagnosticada em função dos sintomas locais. Essas neoplasias são geralmente refratárias aos tratamentos atuais. Uma mulher com 51 anos de idade apresentou dor de cabeça de início súbito, paralisia de braço esquerdo e hipoes tesia facial esquerda. A tomografia e a ressonância magnética revelaram um tumor pituitário invadindo os seios esfenoidal e cavernoso esquerdos. Os dados laboratoriais excluíram hipersecreção hormonal. A paciente foi submetida à cirurgia transesfenoidal, e os achados histológicos mostraram uma neoplasia com Ki-67 estimado em 75%. As imagens excluíram tanto um tumor oculto primário quanto disseminação sistêmica ou do sistema nervoso central. Três semanas após a cirurgia, a condição neurológica apresentou piora com início de ataxia, ptose bilateral, oftalmoplegia e aumento do tamanho da lesão, levando à intervenção cirúrgica por craniotomia, seguida por apenas algumas sessões de radioterapia devido à progressão grave da doença. A paciente veio a óbito depois de quase dois meses das manifestações iniciais. O caso ilustra a agressividade de algumas lesões pituitárias, a eficácia limitada das modalidades atuais de tratamento, como a cirurgia ou a radioterapia, e as limitações da classificação atual de tumores pit...

Metalloproteinases ADAM12 and MMP‐14 are associated with cavernous sinus invasion in pituitary adenomas

“…These data suggest a possible involvement of ADAM12L in the cell proliferation of pituitary adenomas. ADAM12L might play this role by shedding HB‐EGF, thereby enhancing the EGFR‐dependent signaling pathway …”

“…There is controversy in the literature, as considerable variations in Ki-67 immunolabelling (MIB-1 index) of pituitary adenomas have been reported. 36,37 Most researchers found that Ki-67 immunoreactivity was associated with tumor invasiveness in pituitary adenomas and could serve as a prognostic biomarker 36,[38][39][40][41] ; only a few authors drew the opposite conclusions. 42,43 In our study, a significantly higher MIB-1 index was observed in invasive adenomas versus noninvasive pituitary adenomas.…”

“…ADAM12L might play this role by shedding HB-EGF, thereby enhancing the EGFR-dependent signaling pathway. 22,37 MMP-14 is considered to be a highly potent proteinase in tumor biology 44 having multiple functions: (i), MMP-14 degrades basement membrane components and collagens, the main structural determinants of stroma; (ii), MMP-14 has an important regulatory role in the MMP family, as it is well established that MMP-14 leads to activation of other MMPs such as MMP-2, MMP-9 and MMP13 17,45,46 ; (iii), MMP-14 cleaves the hyaluronic acid receptor CD44, leading to phosphorylation of EGF receptor, downstream activation of the MAPK and PI3K signaling pathways and, as a consequence, to enhanced cell migration. 47 In this study, significantly higher mRNA and protein expression levels of MMP-14 were observed in invasive pituitary adenomas, indicating that MMP-14 is likely to be essential for tumor invasion in pituitary adenomas.…”

Progression of an Invasive ACTH Pituitary Macroadenoma with Cushing’s Disease to Pituitary Carcinoma

“…The protein Ki-67 is a cell proliferation marker detected by the monoclonal antibody MIB-1 and is expressed as a percentage of immunopositive nuclei in the form of a Ki-67 proliferation index [ 5 ]. According to Thapar et al Ki-67 over 3% is a criterion to distinguish invasive from noninvasive adenomas with 97% specificity and 73% sensitivity [ 5 , 6 ]. In this case, after 3 years, the adenoma progressed to a carcinoma, as evidenced by p53 expression and diffuse Ki-67 staining.…”

“…Typically, pituitary carcinomas develop craniospinal, lung, liver, and ovary metastases. Immunohistochemical staining of these metastases reveals elevated rates of oncoproteins such as p53 and cell proliferation marker (Ki-67), which is helpful for diagnosis and prognostic relevance in these cases [ 4 , 6 ]. It is worth noting that the levels of those markers are typically higher in metastases than in the primary tumor [ 6 ].…”