Beata Jagielska

Multiple brown tumors in the course of primary hyperparathyroidism mimicking bone metastases – case report

Brown tumours (especially multiple) are uncommon manifestations of primary hyperparathyroidism (PHPT) in developed countries. Although PHTP can cause various symptoms, it can often be mistaken for malignancy. The disease itself (although curable) can lead to disabilities and other serious complications. Herein we report the case of a 65-year-old patient with multiple brown tumours as a very rare first manifestation of normocalcaemic form of primary hyperparathyroidism caused by a giant parathyroid adenoma.

Progressive transformation of germinal centers: an illustration of two clinical cases

Dear Editor, Progressive transformation of germinal centers (PTGC) is a common, but often underdiagnosed cause of benign peripheral lymphadenopathy that is characterized by reactive follicular hyperplasia along with mantle zone lymphocyte expansion into the adjacent sinusoids and germinal centers (GC); the follicles with GC become enlarged and replaced by small lymphocytes from the mantle zone (mainly B cells) [1]. This entity can precede, appear during or after Hodgkin’s lymphoma (HL), mainly nodular lymphocyte predominant Hodgkin’s lymphoma (NLPHL) [2]. The disease itself can also be wrongly diagnosed as early stage NLPHL or follicular lymphoma (FL); therefore, new immunoarchitectural patterns to distinguish between these entities have recently been proposed [1, 2]. We have presented two cases of PTGC along with visual illustrations of the clinical and pathological characteristics. A 32-year-old male presented with painless submandibular and cervical lymphadenopathy. It is worth noting that the patient was under oncological surveillance after a radical distal pancreatectomy due to neuroendocrine pancreatic cancer pT2N0M0 4 years earlier. Upon physical examination, we found enlarged lymph nodes level I, II, and III. Laboratory tests were irrelevant, apart from erythrocyte sedimentation rate (ESR) 22 mm/1 h (1–15) and beta-2-microglobulin 1.96 mg/L (0.7–1.8). We performed an ultrasound (Fig. 1a), which showed hypoechoic, enlarged (to 24 × 20 mm) lymph nodes without visible hilus, one on which a fine needle aspirational biopsy (FNAB) was done. The results of cytopathology were inconclusive—immunohistochemistry (IHC) staining confirmed LCA (+) and CD56 (−), so our further task was to differentiate between reactive lymphadenopathy and low-grade lymphoma. Due to the patient’s history and a suspicion of lymphoma, a PET-CT with FDG was ordered; it revealed an increased uptake of the radiotracer (SUVmax up to 8.9) among many of the cervical lymph nodes (Fig. 1b). Afterwards, a surgical excisional biopsy was done and showed giant, irregular shaped germinal centers with further IHC that confirmed the diagnosis of PTGC. A 65-year-old female presented with a single, painless mass in the submandibular region. The patient was under gastroenterological observation due to primary sclerosing cholangitis and silent coeliac disease. Upon examination, the patient had an enlarged, round, and well-shaped submandibular lesion. An otorhinolaryngology examination did not reveal further findings that would suggest the cause of the lymphadenopathy. Laboratory tests were also irrelevant, apart from elevated beta-2-microglobulin 2.02 mg/L (0.7–1.8). On the ultrasound, we found a hypoechoic lymph node sized 10 × 17 mm with abundant vascularization. A FNAB of the lesion was performed and the cytopathology results suggested a reactive lymphadenopathy and advised a core biopsy in the case of further clinical doubts. A magnetic resonance was ordered to exclude other pathologic findings in the head and neck area. It showed enlarged submandibular (level IB) lymph node that displayed contrast enhancement (Fig. 1c). Due to the vague clinical symptoms and the patient’s preference for lesion removal rather than active surveillance, an excisional biopsy was done. The pathologic report suggested follicular lymphoid hyperplasia with PTGC (Fig. 1D1). The BCL2 (Fig. 1(D3)), BCL6 (Fig. 1(D2)), and CD10 expression was normal. PTGC is quite a common clinical entity that accounts for 3.5% of cases of chronic lymphadenitis [3]. The disease * Konrad Tałasiewicz ktalasiewicz@gmail.com

The analysis of the long-term outcomes of sorafenib therapy in routine practice in imatinib and sunitinib resistant gastrointestinal stromal tumors (GIST)*

Aim of the study was to analyze the outcome of treatment and factors predicting results of sorafenib therapy in inoperable/metastatic CD117-positive GIST patients after failure on imatinib and sunitinib. Material and methods We identified 60 consecutive patients (40 men, 20 women) with advanced inoperable/metastatic GIST after failure on at least imatinib and sunitinib treated in one sarcoma center with sorafenib at initial dose 2 × 400 mg daily in 2007–2015 (in 56 cases it was 3rd line therapy). Median follow-up time was 39 months. Results One year progression-free survival (PFS; calculated from the date of the start of sorafenib to disease progression) rate was 23% and median PFS = 7.7 months. The median overall survival (OS) was 13.5 months calculated from sorafenib start (1-year OS rate = 57%) and 7 years from imatinib start. Three patients (5%) had objective partial responses to therapy, 31 patients (52%) had stabilization of disease > 4 months. Primary tumor mutational status was known in 43 cases (73%), but we have not identified the differences in PFS between tumors carrying different KIT/PDGFRA mutations. The most common adverse events were: diarrhoea, hand and foot syndrome, fatigue, loss of weight and skin reactions; grade 3–5 toxicity occurred in 35% of patients. 23 patients required sorafenib dose reductions due to AEs. Conclusions We confirmed that many advanced GIST patients benefit from sorafenib therapy after imatinib/sunitinib failure with OS > 1 year.

Are molecular target therapies limited by cardiotoxicity — causes and symptoms of cardiovascular damage

Since the introduction of new drugs, (commonly referred to as ‘Molecular Target Therapies’), into oncological clinical practice both the number of objective indicators/endpoints of achieved treatment response and cancer survival duration have increased. Nevertheless, the risk of cardiovascular complications has also risen. Optimistic reports on the relatively low cardiotoxicity of these drugs have been verified through experience. Routine clinical practice has witnessed growing numbers of new drug groups that have different molecular target points and also a varied cardiotoxicity.This paper presents the most important cardiovascular complications associated with the use of molecularly targeted drugs and includes their mechanisms of development.

Results for advanced melanoma therapy with vemurafenib in a Polish drug programme

Introduction. Melanoma is a heterogeneous group of tumours with poor prognosis if the disease is metastatic. More than half of patients with melanoma of the skin have detectable mutations in the BRAF gene. Vemurafenib is the BRAF kinase inhibitor used in the treatment of patients with advanced melanoma with the BRAF mutation. This improves time to progression-free survival and overall survival in patients with this diagnosis. The aim of the study was to analyse the results of treatment and safety of vemurafenib in patients treated during the Polish drug programme. Materials and methods .Between October 2013 and April 2015 a total of 189 patients were treated, 90 women and 99 men, who had previously been diagnosed with unresectable/metastatic melanoma with BRAF V600 mutation. Patients received vemurafenib in 960 mg dose twice per day. The estimated progression-free survival, overall survival and adverse events were assessed. For the survival analysis the Kaplan-Meier method and log-rank test (log-rank) for multi-factor analysis were used. Results. In the first evaluation of the effectiveness of treatment, 8 patients (4.3%) had a complete response, 75 patients (39.7%) partial response, 62 patients (32.8%) had stable disease, and 44 patients (23.2%) had progression of the disease. The disease was controlled in 76.7% of patients. After progression during the therapy with vemurafenib 27% of the patients received subsequent lines of systemic therapy. Twenty-eight patients received chemotherapy and 22 patients immunotherapy with ipilimumab. During the last analysis dated 5 September 2015, the median observation time for still living patients was 8 months (range 3–26). Median progression-free survival was 6.7 months. The median overall survival was 12 months. 146 patients (77%) had adverse events, mostly in the form of dermal toxicity of Grades 1 and 2. Thirty-two patients (17%) presented with side effects of the 3rd and 4th grades of toxicity. Two patients had to stop the treatment due to the toxicity. There were no deaths reported due to the toxicity of treatment. Conclusions. The multicentre analysis confirmed the efficacy and safety of vemurafenib in routine clinical practice in a heterogeneous group of advanced melanomas with BRAF mutation. We confirmed the importance of the known prognostic factors for overall survival in this group of patients, such as lactate dehydogenaze activity (LDH) and ECOG performance status. The current survival of patients with the metastatic melanomas with BRAF mutations are longer than those observed in historical groups.