[Morphological predictors of the efficacy of mitotane therapy in adrenocortical cancer].

BACKGROUND: Adrenocortical cancer (ACC) is an orphan malignant tumor of the adrenal cortex with a predominantly poor prognosis and an aggressive clinical course. Nowadays, mitotane is a non-alternative drug in the treatment of ACC. The search for prognostic parameters that determine the sensitivity of ACC to ongoing treatment is currently an urgent task. Expression levels of the large subunit of ribonucleotide reductase M1 (RRM1), cytochrome P450 2W1 (CYP2W1), and sterol- O-acyltransferase-1 (SOAT1) are considered as potential predictors of response to mitotane therapy. AIM: To assess the immunohistochemical expression of RRM1, CYP2W1 and SOAT1 in ACC as markers of clinical outcomes and response to the therapy with mitotane. MATERIALS AND METHODS: The study included 62 patients older than 17 years of age with a diagnosis of ACC confirmed histologically and immunohistochemically. Mitotane therapy was initiated in 29 patients in the postoperative period, 33 patients were under dynamic observation without concomitant drug treatment. Antibodies to RRM1, CYP2W1, SOAT1 were used diluted in accordance with recommendations of firms-manufacturers for immunohistochemical detection. RESULTS: In the group of patients with low and moderate RRM1, CYP2W1 and SOAT1 immunoreactivity in the tumor and no antitumor therapy, a better DFS was noted (p=0.037, p=0.020 and p=0.001, respectively) compared to the group of patients receiving mitotane therapy at this level of marker expression. With high immunoreactivity of the markers, no statistically significant differences in DFS were found. CONCLUSION: Consistent with the findings in our study, low expression of RRM1, CYP2W1 and SOAT1 was associated with worse DFS with antitumor therapy. The results of the work indicate the need to assess the levels of immunoreactivity of these markers in patients with ACC before starting treatment with mitotane in order to predict the efficiency of therapy.

[Case of clinically "aggressive" course of primary hyperparathyroidism, algorithm of differential diagnosis].

Primary hyperparathyroidism (PHPT) is a significant endocrine disease caused by increased production of parathyroid hormone (PTH) by altered parathyroid glands and violation of the mechanisms of regulation of serum calcium concentrations. These changes can lead to nephrolithiasis, osteoporosis, erosive and ulcerative lesions of the gastrointestinal tract, a number of less specific symptoms (nausea, vomiting, weakness, fatigue, etc.). Etiologically, in more than 85% of cases, PHPT is a consequence of sporadic solitary adenoma or hyperplasia parathyroid glands, however, in 1-3% of cases, the cause is carcinoma of parathyroid glands , including as part of various genetic syndromes. The importance of timely examination for PHPT of patients with characteristic clinical manifestations of this disease and - with an aggressive course - alertness towards carcinomas of parathyroid glands was noted. At the same time, the severity of the clinical picture and even the presence of suspicious signs characteristic of hereditary forms of carcinomas of parathyroid glands are not always a consequence of the malignant process. We present a description of a young patient with a severe course of PHPT, multiple fractures and a voluminous tumor of the upper jaw, developed as a result of a typical adenoma of parathyroid glands. Additionally, the algorithm of pre- and postoperative differential diagnosis for such patients is highlighted.

[Metastatic solid pseudopapillary tumor in the perinephric fat without a primary identified focus]. / Metastaz solidnoi psevdopapillyarnoi opukholi v paranefral'nuyu kletchatku bez pervichno vyyavlennogo ochaga.

Solid pseudopapillary tumor of the pancreas is an extremely rare neoplasm of the exocrine portion of this organ, which affects mostly young women and is characterized by a low malignancy potential and a relatively benign clinical course. According to the literature, even in disease progression as metastases, the overall 5-year survival rate is more than 95%. The paper describes a clinical case of a female patient with a solid pseudopapillary pancreatic tumor regarded as a metastatic neoplasm in the retroperitoneal space after surgical treatment previously performed in 2001.

[Adrenocortical cancer: morphological variants, immunohistochemical characteristics]. / Adrenokortikal'nyi rak: morfologicheskie varianty, immunogistokhimicheskaya kharakteristika.

Adrenocortical cancer (ACC) is a rare endocrine malignancy of the adrenal cortex, which has an unfavorable prognosis and extremely aggressive clinical behavior in most cases. Nevertheless, cases of a more favorable disease course with late metastasis and slow progression have been described. In 2017, the International Agency for Research on Cancer (IARC) and the World Health Organization (WHO) in the 4th edition of the Classification of Tumors of the Endocrine Organs identified histological variants of ACC, such as classical, oncocytic, myxoid, and sarcomatoid ones, indicating the morphological heterogeneity of this tumor. OBJECTIVE: To provide a detailed description of the morphological variants of ACC with an emphasis on their histological characteristics and the expression of immunohistochemical markers. MATERIALS AND METHODS: A total of 75 cases of ACC were analyzed in the adult population diagnosed as having the morphological variants in accordance with the International Histological Classification of Adrenal Tumors (WHO, 2017). Monoclonal antibodies to SF1, Inhibin A, Melan A, Ki-67, p53, and antimitochondrial antibodies were used for immunohistochemical diagnosis. RESULTS: The classic, oncocytic, and myxoid subtypes of ACC were found in 51 (68%), 15 (20%), and 9 (12%) cases, respectively. The functional activity of the tumors was observed in 43% (n=18) in the classic variant of ACC; moreover, the clinical picture was manifested by the symptoms of hypercorticism (38%) and virilization (5%). There were no significant differences in hormonal activity between different morphological variants. The characteristics of the above histological variants of the tumor was determined with a description of growth patterns that can improve the diagnosis of ACC. The diagnosis of ACC can be confirmed by an immunohistochemical study; the required minimum panel of markers should include SF1, Melan A, and Inhibin A. The Ki-67 proliferative activity index showed significant differences (p=0.0056) when it was determined in the morphological variants of ACC. CONCLUSION: Despite the determination of a minimal immunohistochemical panel to confirm the diagnosis of ACC, it is important to remember that each histological variant may be characterized by the different expression of immunohistochemical markers. The identification of morphological variants of ACC and the use of specific, sensitive, and prognostically significant immunohistochemical markers will allow clinicians and pathologists to more accurately judge the biological properties of this tumor and the clinical course of the disease.