Endocrine Abstracts

Taking into account heterogeneity of somatotrophic tumors (STs), intragroup differential diagnostics is of practical importance, since it allows to predict scenario of acromegaly clinical course, as well as the efficacy of secondary drug therapy (DT).The aim of this study was to determine prognostic power of cytological, immunological&radiological predictors of sensitivity/resistance to fg-SRLs in patients with pure somatotropinomas.

Materials and Methods: A retrospective morphological&radiological analysis was carried out in 83 (30m) patients who achieved/did not achieve [IGF-1 index (IGF-1/ULN) >1] acromegaly control against background of long-term secondary DT by fg-SRLs. Immunohistochemical analysis (IHA) included determination of antibodies to GH, Ki-67, CAM5.2, SSTR2& 5. Proportion of cells with presence of fibrous bodies (FB) was ranked according to scores 1-3 (1 – absence, 2 – <70% of cells, 3 – >70% of cells). Additionally, MRI recordings were reanalyzed with quantification of relative tumor signal intensity (RTSI) by comparing the area of interest with gray matter of the brain on T2-weighed MRI (T2-WI). Data obtained were compared with final results of fg-SRLs treatment.

Results: IHA revealed immunophenotypes of densely&sparsely granulated somatotrophic tumor (DGST&SGST) were identified in 41&42 patients, respectively. Microscopy with H&E staining identified several cytological variants of pure somatotropinomas. Among DGSTs,19 (46%) patients had eosinophilic tumors (ETs),22 (54%) – mixed tumors of eosinophilic&chromophobic cells [intermediate type of tumors (ITTs)]. Among SGSTs,29 (66%) patients had chromophobic tumors (CTs),11 (27%) – ITTs and 2 (7%) – ETs. ETs were distinguished by larger number of secretory cells and SSTR2 expression, as well as by smaller initial tumor volume, low proliferative activity and minimal presence of FB in cells. CTs, on the contrary, were distinguished by their larger size, low SSTR2 expression, higher proliferative activity and pronounced presence of FB in cells. ITTs demonstrated intermediate characteristics of expression varying degrees depending on affiliation with DGSTs/SGSTs. When assessing RTSI, it was shown ETs demonstrated hypointense, ITTs – isointense and CTs – hyperintense signal on T2-WI. As for DT results, with similar initial values of IGF-1 index, maximum dose and treatment duration, patients with ETs, ITTs&CTs had drug remission, partial&complete resistance to fg-SRLs, respectively (Table).

Conclusion: Determination of RTSI on T2-WI adds to IHA data, allows to clarify clinicopathological characteristics of STs and identify patients who are known to be sensitive/resistant to fg-SRLs treatment.