Showing papers in "Československá patologie in 2019"

Fumarate hydratase deficient renal cell carcinoma and fumarate hydratase deficient-like renal cell carcinoma: Morphologic comparative study of 23 genetically tested cases.

Abstract: Hereditary leiomyomatosis and renal cell carcinoma-associated renal cell carcinoma (HLRCC)/ fumarate hydratase deficient renal cell carcinoma (FHRCC) is an aggressive tumor defined by molecular genetic changes - alteration in fumarate hydratase (FH) gene. The morphologic spectrum of HLRCC/FHDRCC is remarkably variable. The presence of large nuclei and prominent dark red inclusion-like nucleoli and perinucleolar clearing are considered as helpful morphologic clue. We selected 23 renal neoplasms primarily based on their morphologic features suspicious for HLRCC/FHDRCC. Morphological, basic immunohistochemical, and genetic analysis was performed. The tumors were divided in two groups according to the molecular genetic findings. The first group included 13 tumors with detected FH mutation/LOH (compatible with diagnosis FHRCC), and the second group included 10 tumors without FH mutation/LOH (FH-like RCCs). In the FHRCC group, the vast majority of cases (9/13) had mixed morphology with different architectural growth patterns. All cases showed prominent macronucleoli, and perinucleolar clearing was found in 10/13 cases. Immunohistochemically, 6/7 FHRCC cases were negative for FH antibody, while one case showed strong diffuse FH reactivity. The FH-like RCC group showed more uniform architectural growth pattern. All 10 tumors had prominent macronucleoli, and perinucleolar clearing was present in 8/10 cases. Eight FH-like RCC cases showed diffuse strong positivity for FH, although 2 cases were completely negative for FH. It is evident that neither morphologic feature nor immunohistochemical analysis can be reliably used in routine practice for the diagnosis of HLRCC/FHRCC. In suspected cases, the diagnosis of HLRCC/FHRCC can be confirmed by molecular-genetic testing for FH mutation. It should be noted that the traditionally described morphologic features of HLRCC/FHRCC (prominent eosinophilic macronuclei with perinucleolar halos) can frequently be seen in other renal neoplasms.

The changes of angiogenesis and immune regulations in stromal microenvironment of cutaneous melanomas.

Abstract: Tumour microenvironment contributes to growth and metastasis, where angiogenesis and immune alteration suppressing its effectory function belong to main factors. Our study is focused on an analysis of microvascular density (MVD), quantification of FOXP3+ T regulatory lymphocytes (Tregs) and PD-L1 lymphocytes, which are associated with a tumour-cells immune escape mechanism. We examined 95 cutaneous melanomas devided in four groups according to TNM classification - pT1 (35), pT2 (21), pT3 (21), pT4 (18) and 25 melanocytic nevi as a control group. Investigated parameters were detected on paraffin embedded tissues by indirect immunohistochemistry, and evaluated by light microscope in central (C) and at peripheral regions (P) on a 1mm2 „hot spot“ region (the area of the highest density). We found a significant MVD increase correlating with a stage of disease, mostly at the edge of tumours (p=0,0001). Lymphocytic PD-L1 expresion was increased in melanomas of pT3 and pT4 stages, also predominantly at the periphery of lesions (p=0,0001). Numbers of FOXP3 lymphocytes positively correlated with a melanoma stage, where higher values were observed in central areas (p=0,008). Our study documents that stimulation of angiogenesis and induction of an adaptive immune response correlate with a melanoma stage. The most prominent changes are at the tumour periphery confirming heterogeneity of a tumour stroma, which is more prominent in advanced tumours, and which may contribute to higher agresivity of these stages.

Cytodiagnostics in Pneumology - State of the Art 2019.

Abstract: Pulmonary cytology represents one of the basic diagnostic methods in pneumopathology. It is primarily focused on: 1) assessment of biologic nature of the pathologic process (recommended terminology and classification according to the The Papanicolaou Society of Cytopathology guidelines, 2016), 2) typing of malignant tumors (according to the WHO Classification of Tumours of the Lung, 2015), 3) assessment of mediastinal and hilar lymph nodes (including preoperative staging), 4) attaining adequate material for ancillary testing, 5) bronchoalveolar lavage (BAL) differential cell count and cytopathology studies. The need for sufficient amount of material especially in tumour diagnostics in the era of targeted therapy/personalized medicine is increasing. In pneumocytology, the diagnostic yield is greatly improved by endobronchial ultrasound-guided (EBUS) fine-needle aspiration accompanied by rapid on-site evaluation (ROSE) provided by a cytopathologist. This process gives the possibility to carefully handle and triage the specimen for diagnostic procedures as well as specific ancillary studies. When carcinoma is suspected, both cytology and biopsy specimens should be obtained whenever possible and reviewed together to achieve the highest specificity and diagnostic concordance. If no histology sample is available, attaining adequate material in the cell block becomes crucial, as it enables to carry out immmunohistochemical methods and molecular genetic testing from cytology material. For optimal acquisition, processing and testing of limited specimens in pneumocytology, as well as in pulmonary histopathology, the key issue is to establish and operate a multidisciplinary team including a cytopathologist/surgical pathologist, radiologist and pulmonologist.

Metanephric adenoma. A case report and literature review.

Abstract: Metanephric adenoma is a rare renal tumor with almost exclusively benign behavior, which can clinically and radiologically imitate malignancy. The histological examination is therefore crucial in diagnosis. We report a case of a 69-year-old female with an incidental finding of metanephric adenoma of the left kidney and synchronous clear cell renal cell carcinoma of the contralateral kidney. In the report, we present our experience with this rare tumor and literature review with focusing on differential diagnosis. The histological differential diagnosis of metanephric adenoma includes papillary renal cell carcinoma in adult patients and nephroblastoma (Wilms tumor), particularly in children. Immunohistochemical examination and cytogenetic analyses may be useful in differential diagnosis of these neoplasms.

Inflammatory myofibroblastic tumor of the uterus - case report.

Abstract: Inflammatory myofibroblastic tumor (IMT) of the uterus is rare but probably underdiagnosed tumor. It is usually benign but small fraction of cases may locally recur or rarely metastasize. Herein, we present a case report of 66-year-old patient with uterine IMT originally diagnosed as leiomyosarcoma of the uterus. The patient died within few months due to local tumor progression with skeletal metastases. Macroscopically, this was a voluminous locally aggressive yellowish-grey tumor of soft consistency limited to myometrium. Microscopically, the tumor was characterized by polymorphic spindle cell proliferation with marked nuclear atypia and numerous mitoses. Small geographic necroses was noticed. Typical histologic features of IMT were represented by lymphocytic infiltrate which was only very small and focal. Myxoid stroma was absent. Immunohistochemically, there was strong and diffuse cytoplasmic positivity of ALK (anaplastic lymphoma kinase). The presence of PPP1CB-ALK fusion transcript was confirmed by molecular-genetic methods. Proper diagnosis of uterine IMT is of importance as there is an option of targeted ALK inhibitor therapy in cases of aggressive tumor behaviour. Currently it is thought that histomorphology of uterine IMT may overlap with that of leiomyosarcoma and STUMP (smooth muscle tumor of uncertain malignant potential). The presence of ALK rearrangement is probably the only reliable diagnostic marker. Thus, ALK immunohistochemistry followed by molecular-genetic testing seems to represent suitable screening tool for the detection of uterine IMT.

Atypical fibroxanthoma, rare and often unrecognized cutaneous soft tissue tumor - a case report and review of the literature.

Abstract: Atypical fibroxanthoma (AFX) is a rare cutaneous soft tissue tumor typically occurring in the elderly on sun exposed skin. Histologically, it is composed of pleomorphic, atypical cells with multiple mitoses including atypical mitotic figures resembling undifferentiated malignant tumor. AFX is considered to be a benign tumor with almost uniformly excellent prognosis following conservative therapy if strict diagnostic criteria are applied. We present a case report of 68-year-old man with a skin tumor in the temporo-parietal region. Histomorphological and immunohistochemical analysis led us to the diagnosis of atypical fibroxanthoma. We offer a review of terminology and categorization of this tumor and an overview of immunohistochemical markers useful in differential-diagnostic process to rule out other malignant tumors, because AFX is a diagnosis of exclusion. The correct diagnosis prevents unnecessary overtreatment of the patient.

Chondroblastoma-like primary malignant giant cell tumor of the humerus - a case report.

Abstract: 35-year-old woman suffered prolonged pain in the left shoulder, where an aggressively growing tumor of the proximal humerus was revealed thereafter. The lesion caused massive osteolysis of the metaepiphysis with cortical disruption, but no soft tissue extension was evident. Given the unsatisfactory effect, the ongoing neoadjuvant chemotherapy was prematurely ceased and the resection 13 cm long segment of bone with modular prosthesis replacement followed. Histologically, clear-cut malignant tumor with both the presence of numerous reactive osteoclast-like giant cells and geographic structural deposition of chondroid matrix bore a close resemblance to chondroblastoma. Dominant cellular composition formed solid mosaic clusters of large, atypical, frequently binucleated cells with voluminous eosinophilic cytoplasm. Impressive nuclear pleomorphism was accentuated by both the grooving and atypical mitotic figures. Thorough sampling disclosed limited, but sharply contrasting parts, where biphasic arrangement of small uniform stromal elements together with regularly distributed, reactive osteoclasts suggested putative precursor giant cell lesion. Except the osteoclasts, all matrical and stromal cells were strongly SOX9 and D2-40 positive; in contrary desmin, SATB2, S100 and p63 yielded completely negative results. Detected H3F3A c.103GgT mutation in exon 2 finally established true nature of that peculiar neoplastic proliferation and lead to descriptive term of primary chondroblastoma-like malignant giant cell tumor. In the setting of all the microscopic variability, histogenesis and complex differential diagnosis of skeletal (malignant) giant cell lesions, there are discussed e.g. aggressive/malignant chondroblastoma, chondroblastoma-like osteosarcoma or giant cell-rich osteosarcoma and practical impact of specific mutational analysis results as well.