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Pathology, Research and Practice Aug 2020We describe the case of a human papillomavirus-mediated adenocarcinoma of palatine tonsil in a 51-year-old male. Histologically, the tumor exhibited a predominantly...
We describe the case of a human papillomavirus-mediated adenocarcinoma of palatine tonsil in a 51-year-old male. Histologically, the tumor exhibited a predominantly cribriform and tubular (glandular) growth of cuboidal and columnar cells with moderate amount of pale eosinophilic cytoplasm and oval or spindled nuclei with finely dispersed or coarse chromatin and small to medium-sized nucleoli. Foci of nuclear anaplasia and multinucleation, numerous mitotic figures, and necrosis (individual-cell and confluent) were seen. No squamous differentiation was identified. The tumor cells showed strong expression of CK7, p16 and HPV E6/E7 mRNA transcripts, and were negative for p40, CK5/6, AR, synaptophysin and chromogranin. Next generation sequencing showed 3 variants of unknown significance: FGF3 p.(R44fs); NF1 p.(S749 L) and POLE p. (S1506 L) with variant allele frequencies of 37 %; 20 %, and 17 % respectively. Chromosomal microarray analysis using single nucleotide polymorphism microarray (OncoScan) assay showed whole chromosomal gains of chromosomes 8 and 19, whole chromosomal losses of chromosomes 2 and 16, as well as segmental gains of chromosomes 3q25.31q29 (encompassing the PIK3CA gene), 17q21.31q25.3, 20p13q13.33, Xq28, and segmental losses of chromosomes 1q32.2, 6p25.1p21.1, 11q23.1q24.1, 12p11.22, 12p11.22, 14q24.1q32.33, 17p13.3q21.31 (encompassing the TP53 and NF1 genes). The results highlight the need to consider HPV testing in non-squamous cell carcinomas of the oropharynx.
Topics: Adenocarcinoma; Biomarkers, Tumor; Humans; Male; Middle Aged; Papillomavirus Infections; Tonsillar Neoplasms
PubMed: 32224073
DOI: 10.1016/j.prp.2020.152924 -
Scientific Reports Feb 2023Distant intercellular communication in gliomas is based on the expansion of tumor microtubuli, where actin forms cytoskeleton and GAP-43 mediates the axonal conus...
Distant intercellular communication in gliomas is based on the expansion of tumor microtubuli, where actin forms cytoskeleton and GAP-43 mediates the axonal conus growth. We aimed to investigate the impact of GAP-43 and actin expression on overall survival (OS) as well as crucial prognostic factors. FFPE tissue of adult patients with diffuse and anaplastic gliomas, who underwent first surgery in our center between 2010 and 2019, were selected. GAP-43, Cx43 and actin expression was analyzed using immunohistochemistry and semi-quantitatively ranked. 118 patients with a median age of 46 years (IqR: 35-57) were evaluated. 48 (41%) presented with a diffuse glioma and 70 (59%) revealed anaplasia. Tumors with higher expression of GAP-43 (p = 0.024, HR = 1.71/rank) and actin (p < 0.001, HR = 2.28/rank) showed significantly reduced OS. IDH1 wildtype glioma demonstrated significantly more expression of all proteins: GAP-43 (p = 0.009), Cx43 (p = 0.003) and actin (p < 0.001). The same was confirmed for anaplasia (GAP-43 p = 0.028, actin p = 0.029), higher proliferation rate (GAP-43 p = 0.016, actin p = 0.038), contrast-enhancement in MRI (GAP-43 p = 0.023, actin p = 0.037) and age (GAP-43 p = 0.004, actin p < 0.001; Cx43 n.s. in all groups). The intercellular distant communication network in diffuse and anaplastic gliomas formed by actin and GAP-43 is associated with a negative impact on overall survival and with unfavorable prognostic features. Cx43 did not show relevant impact on OS.
Topics: Adult; Humans; Middle Aged; Actins; Anaplasia; Brain Neoplasms; Connexin 43; GAP-43 Protein; Glioma; Prognosis
PubMed: 36739296
DOI: 10.1038/s41598-023-29298-1 -
Head and Neck Pathology Mar 2022Carcinoma cuniculatum (CC) is a rare variant of squamous cell carcinoma (SCC) that is characterized by minimal cytologic atypia and a unique deeply infiltrative growth... (Review)
Review
Carcinoma cuniculatum (CC) is a rare variant of squamous cell carcinoma (SCC) that is characterized by minimal cytologic atypia and a unique deeply infiltrative growth pattern resembling rabbit burrows (cuniculi). With less than 75 cases reported in the head and neck, the clinical and pathologic spectrum of this entity remains poorly understood. A retrospective review of the clinical and pathologic features of archival cases of oral CC was performed. A total of six cases of oral CC were identified. Age ranged from 25-77 years; the male-to-female ratio was 5:1. All patients had a long-standing history of tobacco and betel-quid consumption. The tumors were distributed in the gingivobuccal sulcus (n = 2), the tongue (n = 2), buccal mucosa (n = 1), and the palate (n = 1). Histology in all cases typically revealed a tumor composed of well-differentiated squamous epithelium, devoid of atypia, lining deeply infiltrative, large-sized, branching, keratin-filled cavities, resembling rabbit-burrows. Dense lymphocytic infiltrates and discharging micro-abscesses were regular features. Underlying bone invasion and lymph node metastasis were observed in 1 patient. One patient with a tongue tumor developed locoregional recurrence at 10 months while none developed distant metastasis. Oral CC is a rare and under-recognized variant of SCC with locally aggressive behavior. Lack of familiarity with this variant exacerbated by the absence of cytologic anaplasia makes CC susceptible to multiple negative biopsies and erroneous diagnoses. Awareness of this clinicopathologic entity is essential to allow its accurate diagnosis and optimal management.
Topics: Animals; Bone Neoplasms; Carcinoma, Squamous Cell; Carcinoma, Verrucous; Female; Humans; Male; Mouth Neoplasms; Neoplasm Recurrence, Local; Rabbits; Tongue Neoplasms
PubMed: 34076846
DOI: 10.1007/s12105-021-01340-6 -
Intractable & Rare Diseases Research Nov 2019Glioneuronal tumors are usually low-grade and have favorable prognosis. The anaplastic glioneuronal tumor with fusion has not yet been documented. This article reports...
Glioneuronal tumors are usually low-grade and have favorable prognosis. The anaplastic glioneuronal tumor with fusion has not yet been documented. This article reports a case of glioneuronal tumor with anaplasia and fusion to illuminate the importance of fusion in high-grade glioneuronal tumors. A ten-year-old boy presented with one year of headache and three months of blurry vision and proptosis. Ophthalmologic evaluation revealed bilateral papilledema. Magnetic resonance imaging showed a large mixed cystic and solid mass in the left frontal lobe of cerebrum. Histologic analysis demonstrated a neoplasm with pseudopapillary growth pattern, focal necrosis, microcalcification, and brisk mitotic activity with a high Ki67 labeling index of focally up to 20%. Immunohistochemical assessment identified a mixed glial and neuronal neoplastic cell population. Molecular studies revealed a fusion. The histological and molecular changes are consistent with an anaplastic glioneuronal tumor with fusion. In view of the fact that the effective, targeted therapies for the tumors with fusion are available, detection of fusion for high-grade glioneuronal tumors is clinically helpful.
PubMed: 31890457
DOI: 10.5582/irdr.2019.01118 -
Journal of Cancer Research and... Jan 2023Medulloblastoma (MB) is a heterogeneous disease, displaying distinct genetic profiles, with specific molecular subgroups. Various clinical, pathological and molecular...
BACKGROUND
Medulloblastoma (MB) is a heterogeneous disease, displaying distinct genetic profiles, with specific molecular subgroups. Various clinical, pathological and molecular variables have been associated with disease outcome and therefore utilised in risk stratification of patients.
OBJECTIVES
To perform molecular classification of medulloblastoma using surrogate immunohistochemistry (IHC) and associate molecular subgroups, histopathological types, and available clinicopathological parameters with overall survival (OS) of MB patients.
RESULTS
This study included 65 medulloblastoma patients. Immunohistochemical staining, using β-catenin YAP1 and GRB2-Associated Binding Protein 1 (GAB1) antibodies was used to classify MB cases into wingless signalling (WNT) activated, sonic hedgehog (SHH) activated, and non-WNT/non-SHH molecular subgroups. The relevant statistical analysis was done using GraphPad Prism version 9.3.0. Histological patterns included classic (40 cases, 62%), desmoplastic nodular (D/N) (14 cases, 22%), large cell/anaplastic (LC/A) (9 cases, 13%), medulloblastoma with extensive nodularity (MBEN) (1 case, 1.5%) and one special subtype, i.e., medulloblastoma with myogenic and melanotic differentiation. Molecular subgroups included WNT (4 cases, 6%), SHH (34 cases, 52%), and non-WNT/non-SHH (27 cases, 42%) subgroups. Histopathological types differed significantly according to tumor location, degree of anaplasia and molecular subgroups. Molecular subgroups differed significantly in age distribution and tumor location. The probability of survival was 78% and 68% after 1 and 2 years, respectively. Infants (<3 years of age), LC/A pattern, and TP53-mutant status among SHH subgroup conferred poor prognosis in our study. At the end of the study (at 65 months of maximum follow-up period) probability of survival was 51%.
CONCLUSIONS
Immunohistochemical analysis helps in molecular classification of medulloblastoma in majority of the cases as well as helps in predicting prognosis and treatment response.
Topics: Infant; Humans; Hedgehog Proteins; Medulloblastoma; Tertiary Care Centers; Prognosis; Cerebellar Neoplasms
PubMed: 38384024
DOI: 10.4103/jcrt.jcrt_1268_22 -
Head and Neck Pathology Dec 2021Oropharyngeal squamous cell carcinoma (SCC) is increasing in incidence and, in Western countries, strongly associated with transcriptionally-active high-risk human...
Oropharyngeal squamous cell carcinoma (SCC) is increasing in incidence and, in Western countries, strongly associated with transcriptionally-active high-risk human papillomavirus (HPV). Within HPV-positive tumors, there is wide morphologic diversity with numerous histologic subtypes of SCC. There are also variable degrees of keratinization, anaplasia, stromal fibrosis, and maturing squamous differentiation. Unlike in the uterine cervix, where associations between HPV types and lineages/sublineages within types have been investigated with some clear correlations identified, little to no data exists for oropharyngeal SCC. In this study, for a large cohort of oropharyngeal SCC patients, we performed RTPCR for high-risk HPV. For the HPV positive patients, we sequenced the DNA of the entire HPV16 genome and determined lineages and sublineages, correlating HPV status, genotype, and HPV16 lineages/sublineages with SCC subtype and various histologic features. Of the 259 patients, 224 (86.5%) were high-risk HPV positive, of which 210/224 (93.8%) were HPV type 16 and 6/224 (2.7%) HPV type 33. Of the four HPV16 lineages, A was the most frequent (192/214 or 89.8%) and of the HPV16 A sublineages, A1 was the most frequent (112/210 or 53.3%). Patients with HPV negative tumors were more often keratinizing vs other types (23/35 or 65.7%) and thus more likely to have more maturing squamous differentiation and stromal desmoplasia. There was no significant correlation between HPV type (16 versus other), between HPV16 lineage (A versus others), or HPV16 A sublineages (A1 or A2 versus others) and morphologic type of SCC nor the various morphologic features of anaplasia/multinucleation, degree of keratinization, nor amount of stromal desmoplasia. In summary, in our cohort, there was no correlation between the type of HPV, the HPV 16 lineage or sublineage, and any of the histologic features or morphologic SCC subtypes.
Topics: Carcinoma, Squamous Cell; Genome, Viral; Genotype; High-Throughput Nucleotide Sequencing; Human papillomavirus 16; Humans; Oropharyngeal Neoplasms; RNA, Messenger; Reverse Transcriptase Polymerase Chain Reaction
PubMed: 33797697
DOI: 10.1007/s12105-021-01318-4 -
Oncology Research and Treatment 2018Dedifferentiated chondrosarcoma (DDC) accounts for a small proportion of chondrosarcomas. They demonstrate aggressive behaviour with a high rate of local recurrence and...
BACKGROUND
Dedifferentiated chondrosarcoma (DDC) accounts for a small proportion of chondrosarcomas. They demonstrate aggressive behaviour with a high rate of local recurrence and systemic progression resulting in poor long-term survival rates. Due to its relatively low incidence, previous studies have grouped different histiotypes together to achieve adequate study numbers for analysis.
METHODS
This retrospective study examines the clinical course and the role of chemotherapy in the subgroup of patients with DDC where osteosarcoma is the predominant dedifferentiated component. Between 2000-2010, 21 patients were identified.
RESULTS
The mean age at presentation was 64 years (range 35-80 years). 12 patients were considered unfit for chemotherapy, whilst 2 patients declined chemotherapy. 5 patients received neoadjuvant chemotherapy, with less than 90% necrosis demonstrated in all these cases. 3 patients received post-operative chemotherapy. The median survival for the entire group was 9.5 months. In the 7 patients who received chemotherapy, the median survival was 17 months, and those who had chemotherapy had a greater median time to local recurrence.
CONCLUSION
This study demonstrates that cytotoxic chemotherapy may be offered to appropriately selected patients.
Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Chondrosarcoma; Disease Progression; Female; Humans; Leukopenia; Male; Middle Aged; Osteosarcoma; Retrospective Studies; Treatment Outcome
PubMed: 29902785
DOI: 10.1159/000487803 -
Clinical Cancer Research : An Official... Jul 2023While patients with intermediate-risk (IR) Wilms tumors now have an overall survival (OS) rate of almost 90%, those affected by high-stage tumors with diffuse anaplasia...
PURPOSE
While patients with intermediate-risk (IR) Wilms tumors now have an overall survival (OS) rate of almost 90%, those affected by high-stage tumors with diffuse anaplasia have an OS of only around 50%. We here identify key events in the pathogenesis of diffuse anaplasia by mapping cancer cell evolution over anatomic space in Wilms tumors.
EXPERIMENTAL DESIGN
We spatially mapped subclonal landscapes in a retrospective cohort of 20 Wilms tumors using high-resolution copy-number profiling and TP53 mutation analysis followed by clonal deconvolution and phylogenetic reconstruction. Tumor whole-mount sections (WMS) were utilized to characterize the distribution of subclones across anatomically distinct tumor compartments.
RESULTS
Compared with non-diffuse anaplasia Wilms tumors, tumors with diffuse anaplasia showed a significantly higher number of genetically distinct tumor cell subpopulations and more complex phylogenetic trees, including high levels of phylogenetic species richness, divergence, and irregularity. All regions with classical anaplasia showed TP53 alterations. TP53 mutations were frequently followed by saltatory evolution and parallel loss of the remaining wild-type (WT) allele in different regions. Morphologic features of anaplasia increased with copy-number aberration (CNA) burden and regressive features. Compartments demarcated by fibrous septae or necrosis/regression were frequently (73%) associated with the emergence of new clonal CNAs, although clonal sweeps were rare within these compartments.
CONCLUSIONS
Wilms tumors with diffuse anaplasia display significantly more complex phylogenies compared with non-diffuse anaplasia Wilms tumors, including features of saltatory and parallel evolution. The subclonal landscape of individual tumors was constrained by anatomic compartments, which should be considered when sampling tissue for precision diagnostics.
Topics: Humans; Kidney Neoplasms; Anaplasia; Retrospective Studies; Phylogeny; Wilms Tumor
PubMed: 37140929
DOI: 10.1158/1078-0432.CCR-23-0311 -
Genes, Chromosomes & Cancer Apr 2024The wide application of RNA sequencing in clinical practice has allowed the discovery of novel fusion genes, which have contributed to a refined molecular classification...
The wide application of RNA sequencing in clinical practice has allowed the discovery of novel fusion genes, which have contributed to a refined molecular classification of rhabdomyosarcoma (RMS). Most fusions in RMS result in aberrant transcription factors, such as PAX3/7::FOXO1 in alveolar RMS (ARMS) and fusions involving VGLL2 or NCOA2 in infantile spindle cell RMS. However, recurrent fusions driving oncogenic kinase activation have not been reported in RMS. Triggered by an index case of an unclassified RMS (overlapping features between ARMS and sclerosing RMS) with a novel FGFR1::ANK1 fusion, we reviewed our molecular files for cases harboring FGFR1-related fusions. One additional case with an FGFR1::TACC1 fusion was identified in a tumor resembling embryonal RMS (ERMS) with anaplasia, but with no pathogenic variants in TP53 or DICER1 on germline testing. Both cases occurred in males, aged 7 and 24, and in the pelvis. The 2nd case also harbored additional alterations, including somatic TP53 and TET2 mutations. Two additional RMS cases (one unclassified, one ERMS) with FGFR1 overexpression but lacking FGFR1 fusions were identified by RNA sequencing. These two cases and the FGFR1::TACC1-positive case clustered together with the ERMS group by RNAseq. This is the first report of RMS harboring recurrent FGFR1 fusions. However, it remains unclear if FGFR1 fusions define a novel subset of RMS or alternatively, whether this alteration can sporadically drive the pathogenesis of known RMS subtypes, such as ERMS. Additional larger series with integrated genomic and epigenetic datasets are needed for better subclassification, as the resulting oncogenic kinase activation underscores the potential for targeted therapy.
Topics: Male; Humans; Adult; Child; Rhabdomyosarcoma; Rhabdomyosarcoma, Embryonal; Rhabdomyosarcoma, Alveolar; Epigenomics; Genomics; Ribonuclease III; DEAD-box RNA Helicases; Receptor, Fibroblast Growth Factor, Type 1
PubMed: 38607246
DOI: 10.1002/gcc.23232 -
Biochemical and Biophysical Research... Jul 2022This study aimed to screen anaplasia-related genes that influence the progression of retinoblastoma (RB) and to identify immune cells associated with the poor prognosis.
OBJECTIVE
This study aimed to screen anaplasia-related genes that influence the progression of retinoblastoma (RB) and to identify immune cells associated with the poor prognosis.
METHODS
Differentially expressed genes (DEGs) between retina and RB samples were acquired from gene expression omnibus (GEO) database. Candidate hub genes were screened by taking intersections among the co-expressed genes, the hub nodes, and DEGs of the validation set. The hub genes were identified by receiver operating characteristic (ROC) and quantitative real-time PCR (qPCR). Immune infiltration levels of RB tissues were estimated using single-sample gene set enrichment analysis (ssGSEA). The functions of RB cells were detected by CCK8, EDU and flow cytometry assays.
RESULTS
665 DEGs involved in the genesis and progression of RB were acquired from GEO database. 29 candidate hub genes were screened by examining 43 co-expressed genes and 63 hub nodes. 9 hub genes (CHEK1, EXO1, FANCI, GTSE1, MELK, MKI67, NCAPH, PRC1, and UBE2T) strongly related to the anaplastic grades were validated by ROC curve analysis (AUC >0.8). Based on the ssGSEA scores, the immune infiltration levels of Th2 cells were positively associated with anaplastic grade. qPCR assay showed that 9 hub genes were upregulated in RB cells, and UBE2T expressed remarkably high. CCK 8, EDU, and flow cytometry assays revealed that UBE2T silencing inhibited the proliferation of RB cells and incited apoptosis.
CONCLUSIONS
The increased infiltration of Th2 cells and upregulated expression of 9 hub genes predict a poor prognosis of RB. UBE2T can be a therapeutic target for RB treatment.
Topics: Biomarkers; Cell Cycle Proteins; Computational Biology; Gene Regulatory Networks; Humans; Microtubule-Associated Proteins; Nuclear Proteins; Prognosis; Protein Serine-Threonine Kinases; Retinal Neoplasms; Retinoblastoma; Th2 Cells; Ubiquitin-Conjugating Enzymes
PubMed: 35594577
DOI: 10.1016/j.bbrc.2022.04.096