Meningiomas represent the most frequently diagnosed intracranial tumors. Inflammation and immune processes may play an important role in therapeutic response as well as in anti- and pro-tumor modulating function. In tumors, inflammatory markers have been able to provide useful prognostic information for treatment or clinical evaluation of patients. The aim of this study was to investigate preoperative hematological markers concerning recurrence or regrowth and clinical variables in meningioma. Eighty nine patients with no corticosteroid therapy were included. Blood tests and tumor characteristics were collected from medical records. Recurrence-free survival was evaluated using Cox regression and Kaplan-Meier curves. Of the 89 cases, 73 (82%) were grade I and 16 (18%) grade II. The mean age was 53±13.9 years, with higher frequency in women, 2:1 proportion. The most frequent subtypes were meningothelial (40.4%), transitional (23.5%) and atypical (17.9%), 64% with peripheral location and 64% had a size greater than 3 cm. Regarding tumor resection, 49 (55.1%) underwent complete surgery (40 remained with tumor (81.6%) and 9 relapse (18.3%)) and 40 (44.9%) submitted to partial resection surgery (29 remained with persistent lesion (72.5%) and 11 regrowth (25%)). In total, 20 (22.4%) cases of recurrence or regrowth were observed. The median recurrence-regrowth free survival (RFS) was 62 months, 96.1% at 1 year, 67.4% at 3 years and 51.2% at 5 years. In univariate analysis, anemia (p=0.04), neutrophilia (p=0.02) and neutrophilis/lymphocyts ratio (NLR) (p=0.03) were associated with an increased risk of recurrence or regrowth and poor RFS. In multivariate, the interaction between anemia and NLR >4 represented a higher risk of recurrence or regrowth (p=0.003). The preoperative presence of anemia, neutrophilia, and NLR was associated with an increased risk of recurrence or regrowth in meningiomas, emphasizing the importance of preoperative evaluation of these parameters.

Meningiomas correspond to 37% of intracranial tumors and are considered the second most common neoplasm of the central nervous system in adults. Most of them are benign with slow growth pattern, common from the fifth decade, more frequent in women and with high recurrence rates. In tumors, there is a reduction in the efficiency of DNA error repair, allowing the proliferation of tumor cells. In this work, we evaluated the protein expression of markers involved in cell synthesis (cyclin D1) and repair of DNA errors (MUTYH, XPF, and XPG) in meningiomas. To date, this is the first study to use the immunohistochemical technique in the evaluation of these repair proteins, relating them to clinical data, tumor variables and recurrence-regrowth free survival. 85 samples were included in the study, patients with a mean age of 52 + 13.3 years, 68% female, in proportion 2:1. Most cases were classified as grade I (79%), meningothelial subtype (38%) and transitional (25%). Regarding surgery, 59% of the patients underwent total resection. Regarding location, the most common was the peripheral (62.2%). Most tumors (64%) were larger than 3cm, with a mean of 3.6±2cm. The median recurrence-regrowth free survival was 67 months (95% CI:57.8-76.6). According to the Kaplan-Meier curve, the recurrence-regrowth free survival rate was 94.4% at 1 year, 76.6% at 2 years and 64.7% at 3 years and 49.4% at 5 years. Grades II and III were prognostic factors for tumor recurrence-regrowth (p<0.05). Cyclin D1 was positive in 92%, 77% in grade I and 23% in grades II and III. A statistically significant relationship was found between cyclin D1 and tumor grade (p = 0.001), with higher expression in grade II and III. Repair proteins were expressed in most meningiomas. MUTYH (63.5%), 43.5% in grades I and 20% in grades II and III, with a significant relationship between grades II and III and, expression 10-50% (p=0.02). Significant association was observed with MUTYH (p=0.001) and XPF (p=0.019). XPF and XPG were associated with grades II and III (p=0.002 and p<0.001) and XPF with size >3cm (p=0.03). There was a positive correlation between XPF and XPG (p= 0.02) and between MUTYH and XPF (p=0.003). XP proteins were related to recurrence-regrowth (p=0.04), but not with recurrence-regrowth free survival. Our results demonstrate the activation of repair pathways and increased cell synthesis in grades II and III in meningiomas. Cellular synthesis and DNA repair markers are important tools to broaden knowledge about the biological behavior of meningiomas.

Introduction: The coexistence of acromegaly and Cushing’s syndrome is quite rare. Case reports with this association have been described in the literature, including both ACTH-dependent and ACTH-independent Cushing’s syndrome. In these cases, when considering ACTH-independent hypercortisolism, the main etiology reported is adrenal adenoma. We will describe the case of an acromegalic patient with ACTH-independent cushing syndrome due to adrenal cortical carcinoma. Clinical Case: A 62-year-old male patient with acromegaly diagnosed by headache investigation. He had a previous medical history of T2DM for 20 years, grade III obesity (BMI 40.3), hypertension, obstructive sleep apnea and depression. Initial investigation showed IGF-1 levels of 818 ng/mL (81–225), GH: 3.39 ng/mL (<0.97), prolactin diluted: 2.578 ng/mL (2.1–17, 7), LH: <0.07 mIU/mL (1.5–9.3), FSH: 0.6 mIU/mL (1.4–18.1), total Testosterone: 51 ng/dL (241- 827) Cortisol at 8 AM: 15 µg/dL, TSH: 1.54 µg/dL (0.55–4.78), free T4: 1.0 ng/dL (0.89–1.76) and brain MRI with a large expansive sella turcica process, invading the right cavernous sinus, with growth to the sphenoid sinus and suprasellar compressing the optic chiasm, suggestive of pituitary macroadenoma. He underwent transsphenoidal resection with histology confirming a prolactin and GH co-secretory pituitary adenoma with Ki-67: 5%. He started treatment with octreotide LAR (30 mg/month) and cabergoline (3.5 mg/week) and underwent 25 radiotherapy sessions. Three years after the diagnosis of acromegaly, the patient underwent CT scan of the abdomen, which identified a 3.8 cm left adrenal nodular lesion that evolved in the 12-month control exam to nodular image with lobulated contours (5.0 x 3.4 cm) and non-contrast phase density > 25 HU. At that time, he had two 24-hour cortisoluria samples: 640.9 and 637 µg/24hs (54–403) and ACTH <5.0 pg/mL (<46).The patient underwent videolaparoscopic adrenalectomy confirming the pathology of the lesion compatible with adrenal cortical carcinoma with invasion of the capsule and peri-adrenal adipose tissue and Ki-67: 20%. Even after primary resection of the adrenal lesion, the patient evolves with local and metastatic progression of the disease, dying a few months later, due to infectious complications of a new surgical approach. Conclusions: To the best of our knowledge, this is the first case of ACTH-independent Cushing’s syndrome caused by adrenocortical carcinoma in an acromegalic patient.

Introduction: Acne fulminans is a rare disease, which most often affects teenagers and young adults, being described associated with exogenous testosterone use and with elevated adrenal androgens in congenital adrenal hyperplasia. We describe a case of acne fulminans in a toddler with adrenocortical carcinoma. Clinical Case: A 2.3 years-old male diagnosed with adrenocortical tumor presenting pubarche, increased penis and body hair, severe acne lesions in face, chest and back and also arterial hypertension. He was previously healthy, with normal development at his first year. The investigation showed adrenal hyperandrogenism and hypercortisolism. Serum values of Total Testosterone >1500 ng/dL (<7,00 - 25,91 ng/dL), ACTH: 7,2 pg/mL (<46 pg/mL), DHEAS: 682 µg/dL (<15 µg/dL), Aldosterone: 11 ng / dL (2.5-39.2 ng /dL), Serum Cortisol 8AM: 30.65µg/dL (5.27 to 22.45 µg/dL), Salivary midnight cortisol: 29.5nmol/L (11:30PM-00:30AM < 7.6 nmol/L). The abdominal computed tomography (CT) showed the left suprarenal gland with a 5,1 x 3,9 cm lesion. Left adrenalectomy was performed, whose histology confirmed adrenocortical carcinoma, without exceeding the capsule, but with a vascular invasion focus and Ki-67 rate of 20%. Hormonal levels in the early follow up were normal and prophylactic corticosteroid therapy was progressively removed. At the three months after surgery outpatient follow-up, worsening of his skin acneiform lesions was observed. He presented painful papules, pustules and crusts at face, chest and back, with purulent exudation and bleeding lesions, associated with axillary and inguinal adenomegaly and acne fulminans was diagnosed. Clinical and ultrasonographic examination also showed the presence of hepatosplenomegaly,. The treatment was initially made with oral corticosteroids and antibiotics. At this time, laboratory tests of androgens, DHEAS and salivary cortisol were normal, but inflammatory markers were high. A new postoperative abdominal CT showed, at the left adrenal topography, two lesions, 47HU attenuation, 1.5 x 1.2 x 1.1cm and 2.3 x 1.7 x 2.0cm, and also confirmed mild hepatosplenomegaly. Biopsy of inguinal lymph nodes was performed, and histology showed lymphoid follicles hyperplasia. Conclusions: This case report showing the association between acne fulminans and adrenocortical carcinoma, at postoperative time, when the child already had normal serum androgens and after hypercortisolism resolution, without oral corticosteroid therapy. Disordered immune response and/or hypersensitivity reaction to Propionibacterium acnes antigens, are also considered as possible triggering factors, although the etiology for this cases is not well established. The description of an acne fulminans case in such a young patient with adrenocortical carcinoma seems unusual and such association deserves further elucidation.