Histiocytic lymphadenopathy secondary to metallosis following endoprosthetic replacement in osteosarcoma patient – a potential diagnostic pitfall

We present the case of a 43-year old patient with inguinal lymphadenopathy 22 years after distal femoral resection for osteosarcoma with cemented distal femoral replacement reconstruction. Seven years after initial distal femoral resection patient underwent metal on metal hip resurfacing arthroplasty on the affected side. Twenty years after distal femoral replacement and 13 years after metal on metal hip resurfacing procedure, the patient underwent left inguinal lymph­adenectomy for an enlarged mass of inguinal lymph nodes on suspicion for a sarcoma recurrence. On microscopic ex­amination, excised lymph nodes were massively infiltrated with macrophages and multinucleated giant cells with focal asteroid bodies. An examination in polarized light revealed numerous metal particles; immunohistochemical stainings confirmed reactive character of changes, and florid metal-related sinus histiocytosis was finally diagnosed. Microscopic assessment of lymph nodes in the course of malignancy is a standard procedure; we present a rare case of non-neoplastic lymph node enlargement due to the late onset of metallosis, which might be a diagnostic challenge

Metylotransferaza EZH2 jako cel terapeutyczny w nowotworach układu chłonnego

EZH2 methyltransferase is the subunit of the PRC2 complex that catalyzes tri-methylation of histone H3 at Lys 27 (H3K27me3). EZH2 is one of the Polycomb proteins that are the main epigenetic factors and are responsible for silencing and inactivating genes. This enzyme has a dual function in cancer - it is an oncogene and a suppressor gene. Abnormalities resulting from overexpression or mutation in EZH2 coding genes have been found in patients suffering from hematological malignancies and solid cancers. Therefore, it is necessary to treat these patients, has begun studies on molecules directed against the PRC2 complex, in particular against EZH1/EZH2. In 2012, a breakthrough in the development of targeted therapy with inhibitors of methyltransferase EZH2 has been the discovery of highly selective compounds containing the 2-pyridine in their chemical structure. In this review, draws attention to the latest findings regarding the oncogenic functions of EZH2 methyltransferase and their impact on the development of tumors. In addition, the text contains current information about preclinical and clinical trials on EZH2 inhibitors testing mainly in hematological cancers.Metylotransferaza EZH2 jest katalityczną podjednostką kompleksu PRC2, która przeprowadza reakcję metylacji lizyny w pozycji 27 histonu 3, prowadząc do powstania jej trimetylowanej formy H3K27me. EZH2 jest jednym z białek Polycomb, które są głównymi czynnikami epigenetycznymi i odpowiadają za wyciszanie i inaktywację genów. Enzym ten pełni podwójną funkcję w etiopatogenezie nowotworów — jest zarówno onkogenem, jak i genem supresorowym. Nieprawidłowości wynikające z nadekspresji bądź mutacji w genach kodujących EZH2 wykazano zarówno u pacjentów chorujących na nowotwory hematologiczne, jak i u osób cierpiących na inne nowotwory. W związku z pojawiającą się potrzebą leczenia takich chorych rozpoczęto badania nad cząsteczkami skierowanymi przeciwko kompleksowi PRC2, w szczególności przeciwko EZH1/EZH2. Przełomowymi w rozwoju terapii celowanej inhibitorami metylotransferazy EZH2 okazało się odkrycie związków silnie selektywnych i zawierających w swojej budowie chemicznej ugrupowanie 2-pirydynowe. W pracy zwrócono uwagę na najnowsze odkrycia dotyczące onkogennych funkcji metylotransferazy EZH2 oraz przedstawiono ich wpływ na rozwój nowotworów. Ponadto zawarto aktualne informacje odnośnie do badań przedklinicznych oraz klinicznych w testowaniu inhibitorów EZH2 głównie w nowotworach hematologicznych.

Histiocytic lymphadenopathy secondary to metallosis following endoprosthetic replacement in osteosarcoma patient – a potential diagnostic pitfall

We present the case of a 43-year old patient with inguinal lymphadenopathy 22 years after distal femoral resection for osteosarcoma with cemented distal femoral replacement reconstruction. Seven years after initial distal femoral resection patient underwent metal on metal hip resurfacing arthroplasty on the affected side. Twenty years after distal femoral replacement and 13 years after metal on metal hip resurfacing procedure, the patient underwent left inguinal lymphadenectomy for an enlarged mass of inguinal lymph nodes on suspicion for a sarcoma recurrence. On microscopic examination, excised lymph nodes were massively infiltrated with macrophages and multinucleated giant cells with focal asteroid bodies. An examination in polarized light revealed numerous metal particles; immunohistochemical stainings confirmed reactive character of changes, and florid metal-related sinus histiocytosis was finally diagnosed. Microscopic assessment of lymph nodes in the course of malignancy is a standard procedure; we present a rare case of non-neoplastic lymph node enlargement due to the late onset of metallosis, which might be a diagnostic challenge.We present the case of a 43-year old patient with inguinal lymphadenopathy 22 years after distal femoral resection for osteosarcoma with cemented distal femoral replacement reconstruction. Seven years after initial distal femoral resection patient underwent metal on metal hip resurfacing arthroplasty on the affected side. Twenty years after distal femoral replacement and 13 years after metal on metal hip resurfacing procedure, the patient underwent left inguinal lymphadenectomy for an enlarged mass of inguinal lymph nodes on suspicion for a sarcoma recurrence. On microscopic examination, excised lymph nodes were massively infiltrated with macrophages and multinucleated giant cells with focal asteroid bodies. An examination in polarized light revealed numerous metal particles; immunohistochemical stainings confirmed reactive character of changes, and florid metal-related sinus histiocytosis was finally diagnosed. Microscopic assessment of lymph nodes in the course of malignancy is a standard procedure; we present a rare case of non-neoplastic lymph node enlargement due to the late onset of metallosis, which might be a diagnostic challenge