15 research outputs found
Subpopulation Treatment Effect Pattern Plot (STEPP) analysis of Ki67 assay according to histology: prognostic relevance for resected early stage ‘pure’ and ‘mixed’ lobular breast cancer
Without Headache: Fever of Unknown Cause Due to Giant Cell Arteritis
Without Headache: Fever of Unknown Cause Due to Giant Cell Arteriti
Well-differentiated neuroendocrine tumor of the urinary bladder expressing GATA 3
Neuroendocrine neoplasms of the urinary bladder are uncommon tumors represented by small-cell neuroendocrine carcinoma and by fewer cases of large-cell neuroendocrine carcinomas and well-differentiated neuroendocrine tumors. Less than 30 examples of this latter entity have been published so far and consisted of clinically indolent lesions mainly located in the bladder neck arranged in a pseudo-glandular architecture often associated with reactive urothelial changes like cystitis cystica/glandularis. Due to their infrequency, pathologists may face difficulty to recognize this proliferation considering it as part of cystitis cystica/glandularis or misinterpreting it as nested urothelial carcinoma, paraganglioma, or secondary bladder involvement by prostatic adenocarcinoma. Herein the case of a 51-year-old female diagnosed with a well-differentiated neuroendocrine tumor of the bladder immunohistochemically expressing GATA3 is reported, pointing out either the pitfall in the differential diagnosis with cystitis cystica/glandularis, nested urothelial carcinoma, and paraganglioma or its usefulness in the differential diagnosis with prostatic adenocarcinoma
Cathepsin K expression in clear cell "sugar" tumor (PEComa) of the lung
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
P16 but not retinoblastoma expression is related to clinical outcome in no-special-type triple-negative breast carcinomas
Triple-negative breast carcinomas represent a tumor group of pivotal clinical importance given the lack of target
therapies. The prognostic significance of triple-negative breast carcinomas remains unclear because of their
histological and molecular heterogeneity. Currently, neither prognostic nor predictive factors are available for
these tumors. Retinoblastoma (Rb) pathway loss has been linked to clinical outcome in various cancer types,
including breast cancer. We investigated the association between Rb and p16 protein expression and clinical
outcome in no-special-type triple-negative breast carcinomas. Immunohistochemical staining for Rb, p16, p53
and CK5 was carried out on a section from archival specimens of 117 no-special-type triple-negative breast
carcinomas. Immunopositive p16 (p16\ufe) and immunonegative Rb (Rb) staining were seen in 49.5% and
in 24.8% of tumors, respectively. There was an inverse correlation between p16\ufe and Rb (Po0.001). P16\ufe
was correlated with G3 grade (Po0.001), high Ki-67 (P\ubc0.03), p53 overexpression (Po0.001) and CK5
immunopositivity (P\ubc0.01). Rb was not associated with any clinicopathologic variable. Follow-up and
therapy data were available in 95 patients. In 20 patients treated with surgery only, neither p16\ufe nor Rb
immunostaining were associated with disease-free survival and overall survival. In 75 patients treated with
adjuvant chemotherapy, p16\ufe was associated with good response to therapy with significant increased
disease-free survival (P\ubc0.001) and showed a trend towards a statistical significance for increased overall
survival (P\ubc0.056); Rb were not associated with disease-free survival and overall survival. In multivariate
analysis, p16\ufe was independently associated with disease-free and overall survival, with a hazard ratio of 0.18
(95% CI: 0.06\u20130.51; P\ubc0.001) and 0.21 (95% CI: 0.06\u20130.74; P\ubc0.015), respectively. In patients with no-specialtype
triple-negative breast carcinomas, p16\ufe is related to good response to adjuvant chemotherapy and can be
considered the best surrogate marker for Rb pathway loss.
Modern Pathology advance online publication, 26 July 2013; doi:10.1038/modpathol.2013.13
STING is a prognostic factor related to tumor necrosis, sarcomatoid dedifferentiation, and distant metastasis in clear cell renal cell carcinoma
: STING is a molecule involved in immune reactions against double-stranded DNA fragments, released in infective and neoplastic diseases, whose role in the interactions between immune and neoplastic cells in clear cell renal cell carcinoma has not been studied yet. We investigated the immunohistochemical expression of STING in a series of 146 clear-cell renal cell carcinomas and correlated it with the main pathological prognostic factors. Furthermore, tumoral inflammatory infiltrate was evaluated and studied for the subpopulations of lymphocytes. Expression of STING was observed in 36% (53/146) of the samples, more frequently in high-grade (G3-G4) tumors (48%,43/90) and recurrent/metastatic ones (75%, 24/32) than in low grade (G1-G2) and indolent neoplasms (16%, 9/55). STING staining correlated with parameters of aggressive behavior, including coagulative granular necrosis (p = 0.001), stage (p < 0.001), and development of metastases (p < 0.001). Among prognostic parameters, STING immune expression reached an independent statistical significance (p = 0.029) in multivariable analysis, along with the stage and the presence of coagulative granular necrosis. About tumor immune-environment, no significant statistical association has been demonstrated between tumor-infiltrating lymphocytes and STING. Our results provide novel insights regarding the role of STING in aggressive clear cell renal cell carcinomas, suggesting its adoption as a prognostic marker and a potentially targetable molecule for specific immunotherapies
Adenocarcinoma of the paraurethral glands: a case report
Adenocarcinoma of the paraurethral glands
represents a very rare neoplasm of the urinary tract. Due
to the rarity of this disease, there is no standard
therapeutic approach. We report a case of adenocarcinoma of the paraurethral glands in a 56-year-old
woman, presenting with abnormal serous vaginal
discharges. The radiologic examination revealed a 5-cm
mass around the urethra, which underwent surgical
resection. After surgical resection, the histology revealed
a moderately differentiated adenocarcinoma, probably
arising from the paraurethral glands. One month later, a
pelvic recurrent mass was radiologically diagnosed;
consequently, an anterior pelvic exenteration with lymph
node dissection was performed. Histological
examination revealed a moderately differentiated
adenocarcinoma, with glandular and micropapillary
architecture, with multiple lymph node metastases. The
absence of modifications such as urethritis cystic
glandularis on the urethral mucosa, as well as the lack of
a lesion in situ, associated with the immunohistochemical expression of PAX8 and negativity for GATA3
and S100p, suggested that the adenocarcinoma
originated from the paraurethral glands rather than from
the urethral mucosa. Post-surgery CT scans revealed no
evidence of metastatic disease.
The patient received 6 courses of adjuvant
chemotherapy with carboplatin and paclitaxel. One year
after the pelvic exenteration, because of inguinal lymph
node progression, an inguinal lymphadenectomy was
performed. Four months later, a TC-PET revealed a
multidistrectual lymph node and a lung micronodule
disease progression.
Invasive micropapillary carcinomas have been
characterized as a rare distinctive variant of carcinomas
in several anatomic sites and are distinguished by a
marked tendency to lymphovascular invasion, justifying
the association with high-stage disease and poor
prognosis. In the present case, both the poor prognosis
connected with micropapillary structure and the lymph
node involvement, encouraged adjuvant cisplatinumbased chemotherapy
Subpopulation Treatment Effect Pattern Plot (STEPP) analysis of Ki67 assay according to histology: prognostic relevance for resected early stage 'pure' and 'mixed' lobular breast cancer
Background: The aim of this analysis was to investigate the potential impact of Ki67 assay in a series of patients affected by early stage invasive lobular carcinoma (ILC) undergone surgery. Methods: Clinical-pathological data were correlated with disease-free and overall survival (DFS/OS). The maximally selected Log-Rank statistics analysis was applied to the Ki67 continuous variable to estimate appropriate cut-offs. The Subpopulation Treatment Effect Pattern Plot (STEPP) analysis was performed to assess the interaction between 'pure' or 'mixed' histology ILC and Ki67. Results: At a median follow-up of 67 months, 10-years DFS and OS of 405 patients were 67.8 and 79.8 %, respectively. Standardized Log-Rank statistics identified 2 optimal cut-offs (6 and 21 %); 10-years DFS and OS were 75.1, 66.5, and 30.2 % (p = 0.01) and 84.3, 76.4 and 59 % (p = 0.003), for patients with a Ki67 < 6 %, between 6 and 21 %, and >21 %, respectively. Ki67 and lymph-node status were independent predictor for longer DFS and OS at the multivariate analysis, with radiotherapy (for DFS) and age (for OS). Ki67 highly replicated at the internal cross-validation analysis (DFS 85 %, OS 100 %). The STEPP analysis showed that DFS rate decreases as Ki67 increases and those patients with 'pure' ILC performed worse than 'mixed' histology. Conclusions: Despite the retrospective and exploratory nature of the study, Ki67 was able to significantly discriminate the prognosis of patients with ILC, and the effect was more pronounced for patients with 'pure' ILC
mTOR eosinophilic renal cell carcinoma: a distinctive tumor characterized by mTOR mutation, loss of chromosome 1, cathepsin-K expression, and response to target therapy
: In the spectrum of oncocytic renal neoplasms, a subset of tumors with high-grade-appearing histologic features harboring pathogenic mutations in mammalian target of rapamycin (mTOR) and hitherto clinical indolent behavior has been described. Three cases (2F,1 M) with histologically documented metastases (lymph node, skull, and liver) were retrieved and extensively investigated by immunohistochemistry, FISH, and next-generation sequencing. Tumors were composed of eosinophilic cells with prominent nucleoli (G3 by ISUP/WHO) arranged in solid to nested architecture. Additionally, there were larger cells with perinuclear cytoplasmic shrinkage and sparse basophilic Nissl-like granules, superficially resembling the so-called spider cells of cardiac rhabdomyomas. The renal tumors, including the skull and liver metastases, showed immunoexpression PAX8, CK8-18, and cathepsin-K, and negativity for vimentin. NGS identified mTOR genetic alterations in the three cases, including the skull and liver metastases. One patient was then treated with Everolimus (mTOR inhibitors) with clinical response (metastatic tumor shrinkage). We present a distinct renal tumor characterized by high-grade eosinophilic cells, cathepsin-K immunohistochemical expression, and harboring mTOR gene mutations demonstrating a malignant potential and showing responsiveness to mTOR inhibitors