Michel Jan

A diagnostic marker set for invasion, proliferation, and aggressiveness of prolactin pituitary tumors

Although most pituitary tumors are benign, some are invasive or aggressive. In the absence of specific markers of malignancy, only tumors with metastases are considered malignant. To identify markers of invasion and aggressiveness, we focused on prolactin (PRL) tumors in the human and rat. Using radiology and histological methods, we classified 25 human PRL tumors into three groups (non-invasive, invasive, and aggressive-invasive) and compared them with a model of transplantable rat PRL tumors with benign and malignant lineages. Combining histological(mitoses and labeling for Ki-67, P53, pituitary transforming tumor gene (PTTG), and polysialic acid neural cell adhesion molecule) and transcriptomic (microarrays and q-RTPCR) methods with clinical data (post-surgical outcome with case-control statistical analysis), we found nine genes implicated in invasion (ADAMTS6, CRMP1, and DCAMKL3) proliferation (PTTG, ASK, CCNB1, AURKB, and CENPE), or pituitary differentiation (PITX1) showing differential expression in the three groups of tumors (P = 0.015 to 0.0001). A case-control analysis, comparing patients in remission (9 controls) and patients with persistent or recurrent tumors (14 cases) revealed that eight out of the nine genes were differentially up- or downregulated (P = 0.05 to 0.002), with only PTTG showing no correlation with clinical course (P = 0.258). These combined histological and transcriptomic analyses improve the pathological diagnosis of PRL tumors, indicating a reliable procedure for predicting tumor aggressiveness and recurrence potential. The similar gene profiles found between non-invasive human and benign rat tumors, as well as between aggressive-invasive human and malignant rat tumors provide new insights into malignancy in human pituitary tumors.

Prognostic Factors in Prolactin Pituitary Tumors: Clinical, Histological, and Molecular Data from a Series of 94 Patients with a Long Postoperative Follow-Up

CONTEXT AND OBJECTIVE Predicting pituitary tumor behavior remains a challenge. This multiparameter investigation aimed to identify markers for recurrence and progression in prolactin tumors. DESIGN From a cohort of patients treated for prolactin tumors by surgery, we retrospectively studied clinical data, tumor characteristics, clinical outcome, and the expression of nine genes by quantitative RT-PCR. RESULTS This study included 94 patients (62 females and 32 men), with long postoperative follow-up periods (mean, 138 +/- 46 months); 54.3% of patients had a macro or giant adenoma. Tumors were classified into three pathological groups based on their radiological and histological characteristics (noninvasive, 61; invasive, 22; and aggressive-invasive, 11). Immediately after surgery, 60 patients (63.8%) went into remission (prolactin level normalization). Persistently elevated prolactin levels (36.2%) were associated with increasing age, male sex, high preoperative prolactin levels, large tumor size on univariate analysis, and invasion and pathological classification on univariate and multivariate (P = 8 x 10(-10) and 3 x 10(-8)) analysis. During follow-up, 19 patients (20%) had tumors that recurred or progressed under dopamine agonist treatment. Invasion and pathological classification were associated with recurrence or progression on univariate analysis. Seven genes (ADAMTS6, CRMP1, PTTG, ASK, CCNB1, AURKB, and CENPE) were associated with tumor recurrence or progression and five of these (ADAMTS6, CRMP1, ASK, CCNB1, and CENPE) were associated with the pathological classification. CONCLUSION This study identifies both the clinical and histological factors that relate to prolactin tumor recurrence or progression. Molecular markers give additional information for prognosis of such tumors. Altogether, our results could influence the management of patients with pituitary tumors.

The interperiosteo-dural concept applied to the perisellar compartment: a microanatomical and electron microscopic study

OBJECT The dura mater has 2 dural layers: the endosteal layer (outer layer), which is firmly attached to the bone, and the meningeal layer (inner layer), which directly covers the brain. These 2 dural layers join together in the middle temporal fossa or the convexity and separate into the orbital, lateral sellar compartment (LSC), or spinal epidural space to form the extradural neural axis compartment (EDNAC). The aim of this work was to anatomically verify the concept of the EDNAC by using electron microscopy. METHODS The authors studied the cadaveric heads obtained from 13 adults. Ten of the specimens (or 20 perisellar areas) were injected with colored latex and fixed in formalin. They carefully removed each brain to allow a superior approach to the perisellar area. The 3 other specimens were studied by microscopic and ultrastructural methods to describe the EDNAC in the perisellar area. Special attention was paid to the dural layers surrounding the perisellar area. The authors studied the anatomy of the meningeal architecture of the LSC, the petroclival venous confluence, the orbit, and the trigeminal cave. After dissection, the authors took photographs of the dural layers with the aid of optical magnification. The 3 remaining heads, obtained from fresh cadavers, were prepared for electron microscopic study. RESULTS The EDNAC is limited by the endosteal layer and the meningeal layer and contains fat and/or venous blood. The endosteal layer and meningeal layer were not identical on electron microscopy; this finding can be readily related to the histology of the meninges. CONCLUSIONS In this study, the authors demonstrated the existence of the EDNAC concept in the perisellar area by using dissected cadaveric heads and verified the reality of the concept of the meningeal layer with electron microscopy. These findings clearly demonstrated the existence of the EDNAC, a notion that has generally been accepted but never demonstrated microscopically.

Lateral sellar angiolipoma: a tumor illustrative of the extradural compartment of the neural axis

Angiolipomas are rare tumors of the CNS that most frequently develop in the orbit, the cavernous space, and the epidural space of the spine. The authors report the case of a patient who presented with an angiolipoma of the cavernous space. Using data from the published literature and an experimental anatomical approach, they demonstrate that the cavernous space contains adipose tissue. Consequently, they suggest that angiolipomas constitute a characteristic tumor illustrating the interperiosteo-dural concept. The authors report the clinical, radiological, and histological data of a patient who presented with a tumor of the cavernous space. In addition, they prepared 2 encephalic extremities (4 cavernous spaces) using a special anatomical preparation consisting of an injection of colored neoprene latex followed by a 6-month immersion in a formaldehyde solution enriched with hydrogen peroxide to soften the bone structures (coronal sections) while leaving the fat in the cavernous space intact. This case report corroborates previously published clinical data and shows that the tumor was a hamartoma comprising mature fat cells associated with vascular proliferation. The tumor developed in the cavernous space, which is an interperiosteo-dural space extending from the sphenoid periosteum (osteoperiosteal layer) to the superior and lateral walls of the cavernous space (encephalic layer). This space represents an anatomical continuum extending from the coccyx to the orbit: the interperiosteo-dural concept. It contains fat tissue that is abundant at the level of the orbit and the epidural spinal space and sparser at the level of the cavernous spaces, as was shown in our anatomical study. The authors suggest that angiolipomas represent a characteristic tumor that illustrates the interperiosteo-dural concept because they essentially develop in the fat tissue contained in these spaces.

Maxillary surgical seeding of a clival chordoma

Abstract Seeding on surgical pathway is a rare form of clival chordoma treatment failure. We report the case of a 42-year-old male with a clival chondroid chordoma removed by a sublabial transsphenoidal approach followed by proton beam radiotherapy, who developed a maxillary bone recurrence 3 years after surgery.