divergent differentiation
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2021 ◽  
Vol 8 ◽  
Author(s):  
Paola Parente ◽  
Antonio Rossi ◽  
Angelo Sparaneo ◽  
Federico Pio Fabrizio ◽  
Antonella Centonza ◽  
...  

Pulmonary carcinoids combined with a non-neuroendocrine component have rarely been described, and this histological subtype is not included as a specific entity in the current World Health Organization classification of pulmonary neoplasms. Here, we described the molecular and histological features of two rare cases of mixed lung neoplasms, composed of atypical carcinoid and adenocarcinoma. The targeted next-generation sequencing analysis covering single nucleotide variations, copy number variations, and transcript fusions in a total of 161 cancer genes of the two different tumor components shows a similar molecular profile of shared and private gene mutations. These findings suggest their monoclonal origin from a transformed stem/progenitor tumor cell, which acquires a divergent differentiation during its development and progression and accumulates novel, specific mutations.


2021 ◽  
Vol In Press (In Press) ◽  
Author(s):  
Abtin Doroudinia ◽  
Siamak Salahi ◽  
Atosa Dorudinia ◽  
Payam Mehrian ◽  
Reza Naseri ◽  
...  

: Most primary small cells carcinoma develop from the lung, and extra-pulmonary small cell carcinoma accounts for less than 5% of all small cell carcinoma cases. In the head and neck region, the most common sites are the larynx and salivary glands; however primary involvement of the palate is extremely rare. The extra-pulmonary small cell carcinoma is similar to its pulmonary counterpart regarding morphology, immunohistochemistry, and electron microscopy features and derives from pluripotential stem cells that develop neuroendocrine features. There is growing evidence regarding the ability of extra-pulmonary small cell carcinoma to arise from pluripotent basilar cells capable of divergent differentiation with the consequence of arising neuroendocrine phenotype as a trans-differentiation phenomenon in the progression of an organ-specific carcinoma. The differentiation between primary and metastatic extra-pulmonary small cell carcinoma is challenging. There is also no standard guideline for treatment as it is a rare occasion, and there is no consensus between radiation oncologists and cancer surgeons about the best treatment strategy. In this study, a very rare case of hard palate small cell carcinoma with neuroendocrine pathology features is presented. To our best of knowledge, this is the third case report of extra-pulmonary small cell carcinoma involving the palate in the literature review. Knowing the clinical presentation and pathology characteristics of such rare tumor in addition to follow-up outcome can be highly useful to establish a reliable guideline for hard palate small cell carcinoma management.


2021 ◽  
pp. 106689692110324
Author(s):  
Fengming Chen ◽  
Shreyas Joshi ◽  
Bradley C. Carthon ◽  
Adeboye O. Osunkoya

Primary urothelial carcinoma (UCa) of the urethra is relatively uncommon, and the underlying pathogenesis has not been well characterized, especially in the absence of concurrent UCa at other sites. A search for cases of primary UCa of the urethra was conducted. Patients with concurrent UCa of the renal pelvis, ureter, or bladder at the time of diagnosis of the primary tumor were excluded. Clinicopathologic and follow-up data were obtained. A total of 35 cases from 30 patients (27 male and 3 female) were included in the study. The mean patient age at the initial diagnosis was 71 years (range: 41-90 years). Cases were composed of high-grade UCa (26 of 35 = 74%), low-grade UCa (4 of 35 = 11%), and UCa in situ (5 of 35 = 14%). Invasion was present in 14 of 26 (54%) cases of high-grade UCa. Interestingly, 23 of 30 (77%) patients had a previous history of UCa including 7 (30%) cases with divergent differentiation or variant histology. Follow-up data were available in 23 patients with a mean duration of 26.7 months (range: 0.6-87 months). Eleven patients (31%) died of metastatic UCa. This is one of the largest studies to date of primary UCa of the urethra without concurrent UCa of the renal pelvis, ureter, or bladder. Previous history of UCa of the bladder, especially with divergent differentiation or variant histology is conceivably a key risk factor for developing subsequent primary UCa of the urethra. These findings are important for the development of surveillance protocols and therapeutic strategies.


2021 ◽  
pp. jclinpath-2021-207573
Author(s):  
Ekaterina Olkhov-Mitsel ◽  
Anjelica Hodgson ◽  
Stanley K Liu ◽  
Danny Vesprini ◽  
Bin Xu ◽  
...  

AimsTo assess the utility of a three-antibody immunohistochemistry panel to classify muscle invasive bladder cancers (MIBCs) in correlation with morphological features and p53 status.MethodsA retrospective review of 243 chemotherapy naïve MIBC cystectomy specimens was performed to assess morphological features. A tissue microarray was sequentially stained with CK5/6, GATA-3 and p16. Subgroups were assigned as basal-like (CK5/6+, GATA3−) and luminal (CK5/6−, GATA3+), with the latter subdivided into genomically unstable (GU, p16+) and urothelial like (Uro, p16−) subgroups. p53 staining was assessed as abnormal/wild type. Cases from the The Cancer Genome Atlas (TCGA) portal were assessed as external validation.ResultsWe identified 78.8% luminal, 21.2% basal cases within our cohort and 63.4% luminal, 36.6% basal in the TCGA dataset. Divergent differentiation (p<0.001) was significantly associated with basal-subtype cases in both cohorts. Within the luminal subgroup (n=186), 81 cases were classified as GU and 105 as Uro. Abnormal p53 staining was noted in 48.0% of basal, 80.2% GU and 38.1% Uro cases. Further, basal-subtype tumours significantly correlated with disease-specific death compared with Uro cases in multivariate survival analysis.ConclusionsThis retrospective study demonstrates the potential utility of a three-antibody immunohistochemistry panel to differentiate luminal and basal MIBC.


Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2615
Author(s):  
Makito Miyake ◽  
Nobutaka Nishimura ◽  
Kota Iida ◽  
Tomomi Fujii ◽  
Ryoma Nishikawa ◽  
...  

The 2016 World Health Organization classification newly described infiltrating urothelial carcinoma (UC) with divergent differentiation (DD) or variant morphologies (VMs). Data comparing oncological outcomes after bladder-preservation therapy using intravesical Bacillus Calmette–Guérin (BCG) treatment among T1 bladder pure UC (pUC), UC with DD (UC-DD), and UC with VMs (UC-VM) are limited. We evaluated 1490 patients with T1 high-grade bladder UC who received intravesical BCG during 2000–2019. They were classified into three groups: 93.6% with pUC, 4.4% with UC-DD, and 2.0% with UC-VM. Recurrence-free, progression-free, and cancer-specific survival following intravesical BCG were compared among the groups using multivariate Cox regression analysis, also used to estimate inverse probability of treatment weighting-adjusted hazard ratio and 95% confidence interval for the outcomes. Glandular differentiation and micropapillary variant were the most common forms in the UC-DD and UC-VM groups, respectively. Of 1490 patients, 31% and 13% experienced recurrence and progression, respectively, and 5.0% died of bladder cancer. Survival analyses revealed the impact of concomitant VMs was significant for cancer-specific survival, but not recurrence-free and progression-free survival compared with that of pUC. Our analysis clearly demonstrated that concomitant VMs were associated with aggressive behavior in contrast to concomitant DD in patients treated with intravesical BCG.


2021 ◽  
Vol 5 (1) ◽  
pp. 009-011
Author(s):  
Rana Chanchal ◽  
Goel Divya ◽  
Singh Akanksha ◽  
Babu Suresh ◽  
Singh Vishwajeet

Bladder carcinomas have a great propensity for divergent differentiation with more that 90% being Transitional cell carcinoma. Several histological variants have been have described so far; they are not only morphologically unique but also have significant prognostic and therapeutic differences making their timely identification of paramount importance. Osteoclastic giant cell variant of urothelial carcinoma is very rare type with controversial management. Studies from China have documented higher incidence and severity of illness in COVID-19 positive cancer patients. We report an unusual case of Osteoclastic giant cell variant of urothelial carcinoma in a 63 yrs old male patient associated with simultaneous COVID-19 infection.


2021 ◽  
pp. 106689692110004
Author(s):  
Hongzhi Xu ◽  
Elizabeth M. Genega ◽  
Liyan Zhuang ◽  
Ming Zhou

Urothelial carcinoma usually shows divergent differentiation and variant histology with squamous and glandular morphology being most common. In this report, we present a case of divergent malignant melanocytic differentiation in a high-grade urothelial carcinoma. A 98-year-old East Asian woman with an anterior bladder wall mass underwent resection, which revealed a high-grade poorly differentiated tumor. A minor component of high-grade papillary urothelial carcinoma and carcinoma in situ is also present. The majority of the tumor cells are morphologically and immunohistochemically consistent with melanoma, a minority of cells are positive for urothelial markers, and rare cells coexpress both melanocytic and urothelial markers. Cells that express melanocytic markers or urothelial markers are intimately admixed together. Taken together, a diagnosis of high-grade urothelial carcinoma with malignant melanocytic differentiation was rendered. This is the first report in the literature of malignant melanocytic differentiation in a high-grade urothelial carcinoma, a finding that may have important diagnostic and therapeutic implications.


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