The new WHO 2016 classification of renal neoplasia encounters the new entity called “clear cell papillary renal cell carcinoma” (ccpRCC). The ccpRCC has been long included as a subtype of clear cell ...RCC histotype and it actually ranges from 2 to 9% in different routinely available cohort of renal carcinomas. Of important note, ccpRCC does not show any recurrences or metastases or lymph-node invasion and the outcome is always good. We reviewed twenty-four publications with available follow-up for patients (no. 362) affected by clear cell papillary RCCs/renal adenomatoid tumours and notably ccpRCC harbors an indolent clinical behavior after a mean of 38 months (3,5 years) of follow-up. This paper reviews the histological, molecular and clinical features characterizing ccpRCC, with the goal of focusing the knowledge of the benign fashion of this new tumour entity, supporting the idea of a new renal cell adenoma recruited morphologically from ex conventional clear cell RCC tumours.
: The current treatment landscape of early stage lung cancer is rapidly evolving, particularly in
mutant non-small cell lung cancer (NSCLC), where target therapy is moving to early stages. In the ...current review, we collected the available data exploring the impact of
targeting in both neoadjuvant and adjuvant settings, underlying
and discussing the existing open issues.
: We performed a comprehensive search using PubMed and the proceedings of major international meetings to identify neoadjuvant/adjuvant trials with
tyrosine kinase inhibitors (TKIs) in NSCLC.
: Limited data are available so far about the activity/efficacy of neoadjuvant TKIs in
mutant NSCLC, with only modest downstaging and pathological complete response rates reported. Differently, the ADAURA trial already proposed osimertinib as a potential new standard of care in resected NSCLC harboring an activating
mutation.
: Anticipating targeted therapy to early stage
mutant NSCLC presents great opportunities but also meaningful challenges in the current therapeutic/diagnostic pathway of lung cancer care. Appropriate endpoint(s) selection for clinical trials, disease progression management, patients' and treatment selection, as well as need to address the feasibility of molecular profiling anticipation, represent crucial issues to face before innovation can move to early stages.
Abstract
The clonal/neoplastic nature of Langerhans cell histiocytosis (LCH) has recently been demonstrated by a high prevalence of BRAF mutations, including pulmonary LCH (PLCH). We hypothesized ...that BRAF-induced senescence, as demonstrated in nevi and melanoma, is involved in the pathogenesis of LCH and PLCH. In a series of pulmonary (19 cases) and non-pulmonary LCH (19 cases), including five aggressive cases, we investigated occurrence of the BRAF V600E mutation by molecular analysis and/or immunohistochemistry using a validated antibody (VE1). The expression of cell-senescence markers p16INK4a and p21CIP1/WAF1 was also immunohistochemically investigated. We demonstrated that 6/19 cases of LCH and 12/19 cases of PLCH were VE1 positive, matching with molecular analysis, and in all cases both p16INK4a and p21CIP1/WAF1 were expressed, irrespective of BRAF mutation status. Interestingly, all the aggressive cases did not express p16INK4a, thus suggesting that loss of senescence control could be related to clinical aggressiveness of LCH, as in melanoma.
The report of cases of lung squamous cell cancers harboring anaplastic lymphoma kinase (ALK) gene rearrangements raises the question whether this histologic subtype should be also evaluated for such ...molecular predictive test.
A consecutive series of 40 lung pure squamous cell carcinomas were analyzed for ALK gene status by fluorescence in situ hybridization. Squamous differentiation was validated using an immunohistochemical panel including n-p63 (p40), cytokeratin (CK) 5/6, sex-determining region Y (SRY)-Box2 (SOX2), thyroid transcription factor 1, CK7, and Napsin-A.
Squamous differentiation was confirmed in all tumors as they stained positive for n-p63 and CK5/6 and negative for thyroid transcription factor 1 and Napsin-A. One of 40 cases (2.5%) showed an ALK rearrangement on fluorescence in situ hybridization analysis.
ALK translocation may be found in lung pure squamous cell carcinomas. Our data suggest the opportunity to test ALK rearrangements on biopsy samples harboring squamous cell cancer differentiation.
Lobular breast carcinoma usually shows poor responsiveness to chemotherapies and often lacks targeted therapies. Since FGFR1 expression has been shown to play pivotal roles in primary breast cancer ...tumorigenesis, we sought to analyze the status of FGFR1 gene in a metastatic setting of lobular breast carcinoma, since promising FGFR1 inhibitors has been recently developed.
Fifteen tissue metastases from lobular breast carcinomas with matched primary infiltrative lobular breast carcinoma were recruited. Eleven cases showed loco-regional lymph-nodal and four haematogenous metastases.FGFR-1 gene (8p12) amplification was evaluated by chromogenic in situ hybridization (CISH) analysis. Her-2/neu and topoisomerase-IIα gene status was assessed. E-cadherin and Hercept Test were also performed. We distinguished amplification (>6 or cluster of signals) versus gains (3-6 signals) of the locus specific FGFR-1 gene.
Three (20%) primary lobular breast carcinomas showed >6 or cluster of FGFR1 signals (amplification), six cases (40%) had a mean of three (range 3-6) chromogenic signals (gains) whereas in 6 (40%) was not observed any abnormality. Three of 15 metastasis (20%) were amplified, 2/15 (13,4%) did not. The ten remaining cases (66,6%) showed three chromogenic signals.The three cases with FGFR-1 amplification matched with those primary breast carcinomas showing FGFR-1 amplification. The six cases showing FGFR-1 gains in the primary tumour again showed FGFR-1 gains in the metastases. Four cases showed gains of FGFR-1 gene signals in the metastases and not in the primary tumours. Her-2/neu gene amplification was not observed in all cases but one (6%) case. Topoisomerase-IIα was not amplified in all cases.
1) a subset of metastatic lobular breast carcinoma harbors FGFR-1 gene amplification or gains of chromogenic signals; 2) a minor heterogeneity has been observed after matching primary and metastatic carcinomas; 3) in the era of tailored therapies, patients affected by the lobular subtype of breast carcinoma with FGFR1 amplification could be approached to the new target biological therapy such as emerging FGFR-1 inhibitors.
Clear cell “sugar” tumor is a rare benign neoplasm arising in the lung, considered as a part of the PEComa family. As PEComas of other sites, this tumor expresses melanocytic markers such as HMB45 ...and Melan-A. Despite cathepsin K, MITF and CD68 staining are known to be positive in a large number of PEComas and
TFE3
rearrangement has been reported in a subset of PEComas, no data is available regarding the expression of these markers and the occurrence of
TFE3
and
TFEB
rearrangement in clear cell “sugar” tumor of the lung. We have investigated the immunolabeling of cathepsin K, MITF, and CD68 in five cases of clear cell “sugar” tumor. Moreover, we have also sought the presence of
TFE3
and
TFEB
rearrangement by fluorescence in situ hybridization (FISH) assay. In all tumors, strong immunoreactivity of cathepsin K and CD68 (PG-M1 and KP1 clone) was demonstrated, whereas none of them labeled for MITF staining and showed
TFE3
or
TFEB
rearrangement. These findings widen the immunohistochemical profile of clear cell “sugar” tumor providing useful new markers for challenging cases. The expression of lysosomal markers, such as cathepsin K and CD68, strengthens the hypothesis that this tumor is part of the PEComa family.
Abstract Background Radical orchiectomy specimens present a unique set of challenges for pathology assessment owing to their rarity and complexity. This study compares second opinion pathology ...reports generated at a single, large academic institution to primary reports from outside hospitals. Methods A database search was conducted for orchiectomy cases that were sent to our institution for management of testicular cancer from 2014 to 2015. Cases sent for consultation without a finalized diagnosis from the outside hospitals were excluded. A total of 221 consecutive cases were evaluated for comparison of final diagnoses between the outside institution and central pathology review. Results This study revealed significant discrepancy involving multiple parameters between original and second opinion pathology reports. Of 221 cases of germ cell tumors assessed, 31% showed some discrepancy of histologic subtype. Overall, reporting of lymphovascular invasion changed in 22% of cases; of those, initially called positive 23% were changed to negative and of those initially called negative 12% were changed to positive. Although the overall discrepancy for spermatic cord invasion was 9%, an initial positive diagnosis was negated 35% of the time. The pathologic stage was altered in 23% of cases, mostly secondary to differences interpreting lymphovascular and spermatic cord invasion. Conclusion Pathologists evaluating orchiectomy specimens should be aware of the major pitfalls in classification and staging, many of which may affect patient management.
•2022 WHO classification of urogenital tumours reclassifies Renal Cell Carcinoma.•Molecularly-defined RCC are introduced for the first time.•We analyze potential personalized therapies for these new ...entities.
The new WHO classification of urogenital tumours published in 2022, contains significant revisions upon the previous 2016 version regarding Renal Cell Carcinoma (RCC). While the most common histotype remains almost untouched, some of the main novelties concerns papillary RCC and oncocytic neoplasms. The main change is the introduction of a new category of molecularly-defined RCC, which includes TFE3-rearranged RCC, TFEB-rearranged, and TFEB-amplified RCC, FH-deficient RCC, SDH-deficient RCC, ALK-rearranged RCC, ELOC (formerly TCEB1)-mutated RCC, SMARCB1 (INI1)-deficient RCC. In this paper we analyze the current knowledge on emerging entities and molecularly-defined RCC to assess whether the current pathological classification offers the oncologist the possibility of selecting more specific and personalized treatments, from both those currently available, as well as those that will soon be available.
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