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BACKGROUND: Prostate biopsy (Bx) sampling-based diagnosis of prostate cancer (PCa) has well-described inaccuracy when compared against whole gland analysis upon prostatectomy. Although upgrading of PCa Grade Group (GG) is often described, the occurrence and prognostic implications of downgrading PCa GG at the time of radical prostatectomy (RP) is less understood. Our objective was to evaluate whether downgrading PCa GG at the time of RP was associated with future tumor behavior. METHODS: The SEER database was searched from 2010 to 2017 and patients were included if they were assigned pathological grades on both Bx and RP specimen. Patients were stratified into Bx GG > RP GG and Bx GG ≤ RP GG groups, and tumor behavior after treatment was examined. Cox regression was used for the survival analysis. RESULTS: Here, 99,835 patients were included in this study. A total of 18,516 (18.5%) patients encountered downgrading from Bx GG to RP GG. A downgrading of 1 grade occurred in 13,969 (75.4%) of these patients and of 2 or more grades occurred in 4547 (24.6%) patients. A history of higher Bx GG compared with RP GG increased the risk of cancer-specific mortality (CSM) for each given RP GG controlling for age, race, preop prostate-specific antigen level, percentage of positive biopsy cores, and pathologic TNM stages. Specifically, a history of high Bx GG conferred a 45% increased risk of CSM for any given RP GG (hazard ratio = 1.45 95% confidence interval = 1.16-1.82, p < 0.001). CONCLUSION: A history of higher Bx GG, and hence downgrading at the time of RP, demonstrates some value as a risk-stratification tool for future cancer outcomes after prostatectomy.
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Próstata , Neoplasias de la Próstata , Masculino , Humanos , Próstata/cirugía , Próstata/patología , Clasificación del Tumor , Prostatectomía , Neoplasias de la Próstata/cirugía , Neoplasias de la Próstata/patología , Biopsia , Estudios RetrospectivosRESUMEN
PURPOSE OF REVIEW: The aim of the review is to provide an update on the current and evolving approaches to diagnosing the challenging clinical entity of renal oncocytoma. RECENT FINDINGS: Renal oncocytoma is being increasingly recognized among patients with renal masses, and it can be found in up to 50% of benign small renal masses (SRMs) less than 4âcm. Renal oncocytomas have benign clinical biology but distinguishing them from some of the other renal masses with more malignant potential can be challenging due to overlapping imaging, histologic, and immunophenotypic characteristics. Increasing integration of various imaging modalities, histologic characteristics, cytogenetics, and molecular and metabolic signatures is helping better define and characterize renal masses. SUMMARY: Evolving and complementary diagnostic approaches, including at the molecular level, are continuing to help refine the classification of renal tumors, with implications on their clinical behavior and ultimately clinical management.
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Adenoma Oxifílico , Carcinoma de Células Renales , Neoplasias Renales , Adenoma Oxifílico/diagnóstico por imagen , Adenoma Oxifílico/patología , Carcinoma de Células Renales/patología , Diagnóstico Diferencial , Humanos , Neoplasias Renales/diagnóstico por imagen , Neoplasias Renales/patologíaRESUMEN
The TNF receptor superfamily member Fn14 is overexpressed by many solid tumor types, including glioblastoma (GBM), the most common and lethal form of adult brain cancer. GBM is notable for a highly infiltrative growth pattern and several groups have reported that high Fn14 expression levels can increase tumor cell invasiveness. We reported previously that the mesenchymal and proneural GBM transcriptomic subtypes expressed the highest and lowest levels of Fn14 mRNA, respectively. Given the recent histopathological re-classification of human gliomas by the World Health Organization based on isocitrate dehydrogenase 1 (IDH1) gene mutation status, we extended this work by comparing Fn14 gene expression in IDH1 wild-type (WT) and mutant (R132H) gliomas and in cell lines engineered to overexpress the IDH1 R132H enzyme. We found that both low-grade and high-grade (i.e., GBM) IDH1 R132H gliomas exhibit low Fn14 mRNA and protein levels compared to IDH1 WT gliomas. Forced overexpression of the IDH1 R132H protein in glioma cells reduced Fn14 expression, while treatment of IDH1 R132H-overexpressing cells with the IDH1 R132H inhibitor AGI-5198 or the DNA demethylating agent 5-aza-2'-deoxycytidine increased Fn14 expression. These results support a role for Fn14 in the more aggressive and invasive phenotype associated with IDH1 WT tumors and indicate that the low levels of Fn14 gene expression noted in IDH1 R132H mutant gliomas may be due to epigenetic regulation via changes in DNA methylation.
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Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Glioma/genética , Glioma/metabolismo , Mutación , Receptor de TWEAK/metabolismo , Biomarcadores de Tumor/metabolismo , Encéfalo/metabolismo , Encéfalo/patología , Neoplasias Encefálicas/patología , Línea Celular Tumoral , Citocina TWEAK/metabolismo , Metilación de ADN , Regulación Neoplásica de la Expresión Génica , Glioma/patología , Humanos , Isocitrato Deshidrogenasa/genética , Clasificación del Tumor , ARN Mensajero/metabolismo , Estudios RetrospectivosRESUMEN
BACKGROUND: Knowledge of topographic skin thickness is important to plastic surgery of the face as it may guide resection and restoration in oncologic, aesthetic, and reconstructive procedures. OBJECTIVE: The purpose of this study is to report the relative thickness of the face throughout 39 distinct subunits. METHODS: Full-thickness punch biopsy samples were obtained at 39 predetermined anatomic locations of the face from 10 human cadaveric heads. Tissue was fixed in paraffin-embedded slides and analyzed using triplicate measurement of dermis and epidermis using computerized measurements. Data were analyzed using univariate statistical analysis and expressed as mean thickness values and relative thickness (RT) values based on the thinnest portion of the face. RESULTS: The area of the face with the thickest dermis was the lower nasal sidewall (1969.2 µm, dRT: 2.59), and the thinnest was the upper medial eyelid (758.9 µm, dRT: 1.00). The area with the thickest epidermis was the upper lip (62.6 µm, eRT: 2.12), and the thinnest was the posterior auricular skin (29.6 µm, eRT: 1.00). Our results confirm that eyelid skin is the thinnest in the face. The thickest portions of the skin appeared to be in the lower nasal sidewall, but the measurements are comparable to those in the ala and posterior auricular skin, which are novel findings. CONCLUSIONS: The greatest epidermal, dermal and total skin thickness are found in the upper lip, right lower nasal sidewall, and left lower nasal sidewall respectively. The least epidermal skin thickness is in the posterior auricular skin. The least dermal skin thickness, and the least total skin thickness, are both in the upper medial eyelid.
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Epidermis/anatomía & histología , Cara/anatomía & histología , Anciano , Anciano de 80 o más Años , Análisis de Varianza , Biopsia con Aguja , Cadáver , Femenino , Humanos , Masculino , Sensibilidad y Especificidad , Piel/anatomía & histologíaRESUMEN
Importance: African American men experience greater prostate cancer incidence and mortality than White men. Growing literature supports associations of neighborhood disadvantage, which disproportionately affects African American men, with aggressive prostate cancer; chronic stress and downstream biological impacts (eg, increased inflammation) may contribute to these associations. Objective: To examine whether several neighborhood disadvantage metrics are associated with prostate tumor RNA expression of stress-related genes. Design, Setting, and Participants: This cross-sectional study leveraged prostate tumor transcriptomic data for African American and White men with prostate cancer who received radical prostatectomy at the University of Maryland Medical Center between August 1992 and January 2021. Data were analyzed from May 2023 to April 2024. Exposures: Using addresses at diagnosis, 2 neighborhood deprivation metrics (Area Deprivation Index [ADI] and validated bayesian Neighborhood Deprivation Index) as well as the Racial Isolation Index (RI) and historical redlining were applied to participants' addresses. Self-reported race was determined using electronic medical records. Main Outcomes and Measures: A total of 105 stress-related genes were evaluated with each neighborhood metric using linear regression, adjusting for race, age, and year of surgery. Genes in the Conserved Transcriptional Response to Adversity (CTRA) and stress-related signaling genes were included. Results: A total of 218 men (168 [77%] African American, 50 [23%] White) with a median (IQR) age of 58 (53-63) years were included. African American participants experienced greater neighborhood disadvantage than White participants (median [IQR] ADI, 115 [100-130] vs 92 [83-104]; median [IQR] RI, 0.68 [0.34-0.87] vs 0.11 [0.06-0.14]). ADI was positively associated with expression for 11 genes; HTR6 (serotonin pathway) remained significant after multiple-comparison adjustment (ß = 0.003; SE, 0.001; P < .001; Benjamini-Hochberg q value = .01). Several genes, including HTR6, were associated with multiple metrics. We observed higher expression of 5 proinflammatory genes in the CTRA with greater neighborhood disadvantage (eg, CXCL8 and ADI, ß = 0.008; SE, 0.003; P = .01; q value = .21). Conclusions and Relevance: In this cross-sectional study, the expression of several stress-related genes in prostate tumors was higher among men residing in disadvantaged neighborhoods. This study is one of the first to suggest associations of neighborhood disadvantage with prostate tumor RNA expression. Additional research is needed in larger studies to replicate findings and further investigate interrelationships of neighborhood factors, tumor biology, and aggressive prostate cancer to inform interventions to reduce disparities.
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Negro o Afroamericano , Neoplasias de la Próstata , Blanco , Anciano , Humanos , Masculino , Persona de Mediana Edad , Negro o Afroamericano/estadística & datos numéricos , Negro o Afroamericano/genética , Estudios Transversales , Maryland/epidemiología , Características del Vecindario , Prostatectomía/estadística & datos numéricos , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/cirugía , Características de la Residencia/estadística & datos numéricos , Estrés Psicológico/genética , Blanco/genética , Blanco/estadística & datos numéricosRESUMEN
Although uterine leiomyosarcoma (ULMS) is a rare disease, it accounts for a significant proportion uterine cancer-related deaths due to frequent metastasis and chemoresistance. The WHO currently recognizes the conventional (spindle), myxoid, and epithelioid variants of ULMS, the latter of which is the rarest, least understood, and cited as clinically more aggressive than the other variants. Descriptions of the histologic features of epithelioid ULMS are extremely limited, and are absent from the cytology literature which has only published descriptions of conventional ULMS or epithelioid variants of other LMS primaries. Therefore, we present a unique case of metastatic epithelioid ULMS to an unusual location, the pancreas, along with its cytologic features on endoscopic ultrasound-guided fine needle aspiration not previously described including pseudoglandular arrangements, scant cytoplasm, and frequent molding.
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Páncreas , HumanosRESUMEN
A 57-year-old man developed a mesothelial proliferation in the peritoneum, several months after he was diagnosed with biopsy-proven epithelioid mesothelioma of the pleura and having undergone several treatments with checkpoint inhibitor immunotherapy. The differential diagnosis was metastatic mesothelioma from the lung primary, versus a reactive process. A diagnosis of atypical mesothelial proliferation was made. Follow-up CT showed no evidence of abdominal disease 5 months later. The complication of serositis following checkpoint inhibitor therapy is reviewed, as well as the differential diagnosis between reactive mesothelial hyperplasia and epithelioid mesothelioma.
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Sarcomatoid mesotheliomas can be challenging to diagnose on small biopsy specimens, where limited material may preclude definitive assessment of invasion and lesional cells can have relatively bland cytology with no mesothelial marker expression. We report a case of a patient who presented with a pleural effusion and had subsequent pleural biopsy that showed a bland, uniform spindle cell proliferation in a mildly myxoid background. There was little if any collagen; no chest wall, soft tissue, or fat; and mesothelial markers were negative. The cells were positive for pancytokeratin and GATA3 by immunohistochemistry, and in situ hybridization showed a "negative" result for homozygous loss of CDKN2A; however, there was partial (heterozygous) loss of one allele. A diagnosis of atypical spindle cell proliferation was made based on these findings. Several months later, the patient had a repeat pleural biopsy that showed spindled cells with more pleomorphism, areas of invasion into the chest wall, and the same partial loss of CDKN2A, consistent with a sarcomatoid mesothelioma. This case underscores the challenges present on small biopsy specimens, the fact that sarcomatoid mesotheliomas can be relatively bland appearing with focal pleomorphism, and that heterozygous loss of CDKN2A should be considered a positive result indicative of a neoplastic process.
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Immune checkpoint inhibitors such as nivolumab increase the T-cell destruction of malignancies but can also trigger a broad variety of immune-related adverse events (irAEs). Colitis as an irAE is well-documented, but upper gastrointestinal tract involvement is primarily unrecognized. We present a patient who developed gastritis as an irAE after multiple cycles of nivolumab and initially responded well to steroid therapy but then developed superimposed cytomegalovirus infection. The similarity between both presentations highlights the importance of having a broad differential diagnosis in patients with gastrointestinal complaints treated with immune checkpoint inhibitors and the need for further studies to better characterize gastritis as an irAE.
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BACKGROUND: Malignant melanoma is an aggressive tumor defined by some histopathologic variables which dictate its behavior and vary in different populations. To date, no data exist on these histopathologic characteristics in Ethiopian Patients. OBJECTIVE: To describe histopathologic features of primary cutaneous melanoma in Ethiopian patients. METHOD: In an attempt to define these features, histologic slides and patient record forms of cases diagnosed as primary cutaneous malignant melanoma were retrieved from records of the Pathology Department of Tikur Anbessa Specialized Teaching Hospital. From the patient records demographic variables including age, sex and anatomic location were documented. The histologic slides were revised for pathologic parameters like, histologic type, depth of invasion, host lymphocytic infiltration and pigmentation. RESULTS: A total of 50 cases of primary cutaneous malignant melanoma were diagnosed in the period of 1999-2005 in Tikur Anbesa Hospital, pathology department. There were equal numbers of male and female patients; the mean age was 51.6 years. Most of the melanomas (64%) were located on the foot. The vast majority (96%) of the cases were nodular melanomas while there was one case of acral lentiginous melanoma and another case of superficial spreading melanoma. Seven (14%) were nonpigmented melanomas. The prognosis was poor with 72% of the cases showing Clark level V invasion and mean Breslow tumor thickness of 6.02mm. Ulceration was present in the majority (83.3%) of the cases. CONCLUSION: Melanoma in Ethiopian patients is characterized by late stage presentation associated with poor prognosis and high preponderance to the foot. The higher prevalence of nodular melanomas with deep vertical invasion support the argument that this type might be a result of progression of other forms as most of our cases were late stage melanomas.
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Melanoma/patología , Neoplasias Cutáneas/patología , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Población Negra , Etiopía/epidemiología , Femenino , Hospitales Universitarios , Humanos , Masculino , Registros Médicos , Melanoma/epidemiología , Persona de Mediana Edad , Pigmentación , Pronóstico , Índice de Severidad de la Enfermedad , Distribución por Sexo , Neoplasias Cutáneas/epidemiología , Úlcera Cutánea/patología , Adulto JovenRESUMEN
Human Immunodeficiency Virus (HIV)-related Opportunistic Infections (OI), including Pneumocystis jiroveci pneumonia (PCP), have become much less commonplace with anti-retroviral therapy (ART). Despite this, OIs are still common and it is important to remain vigilant for their presence and be aware of how ART and OI chemoprophylaxis may lead to atypical disease presentations. We present the case of a 51-year-old woman with HIV and CD4+ T helper lymphocytes cell count > 200 cells/ul on both ART and trimethoprim/sulfamethoxazole prophylaxis who presented with cavitating lung masses, mediastinal lymphadenopathy and pleural effusions. Negative bronchoalveolar lavage (BAL) and transbronchial biopsy (TBBx) prompted a second diagnostic procedure with a transthoracic core needle biopsy; the final diagnosis was granulomatous PCP. This case showcases a very rare presentation of PCP, with both large cavitating lung masses on imaging and granulomatous reaction on pathology, as well as the challenge of a potentially missed diagnosis with negative BAL and TBBx requiring transthoracic core needle biopsy for a final diagnosis.
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OBJECTIVES: The nested variant of urothelial carcinoma (NVUC) is a rare bladder tumor that may possess a luminal molecular phenotype. We sought to determine whether a small immunohistochemical (IHC) panel using common surrogates for molecular phenotypes would reliably classify a cohort of pure NVUC cases. METHODS: IHC staining with a panel composed of markers for basal subtypes (CK5/6, CK14) and luminal subtypes (FOXA1, GATA3) was performed on pure small NVUC cases (n = 23) and 5 large NVUC cases (n = 5). Scoring of IHC stains was performed semiquantitatively. Individual cases were analyzed using previously reported IHC-based surrogates for molecular subtype. RESULTS: The phenotype of NVUC was classified as luminal from 60.1% (FOXA1+/CK5/6-) to 100% (GATA3+/CK14-) of cases using composite phenotypes. No cases possessed a basal or squamous cell carcinoma-like phenotype. The majority of small NVUC cases (69.5%) showed subset CK5/6 expression distinctly localized to the basal layers of tumor cell nests. Intratumoral heterogeneity was also noted in CK5/6 (21.7% of small NVUC cases) but no other markers. CONCLUSIONS: NVUC appears to express markers of both basal and luminal bladder tumors. Definitive gene expression profiling may be valuable to further characterize this unique histologic variant.
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Biomarcadores de Tumor/metabolismo , Carcinoma de Células Transicionales/patología , Queratina-5/biosíntesis , Queratina-6/biosíntesis , Neoplasias de la Vejiga Urinaria/patología , Anciano , Carcinoma de Células Transicionales/clasificación , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Neoplasias de la Vejiga Urinaria/clasificaciónRESUMEN
Nested variant of urothelial carcinoma is a rare variant of urothelial carcinoma morphologically characterized by infiltrative nests of cytologically bland urothelial cells. It is widely recognized that nested variant of urothelial carcinoma can closely mimic von Brunn nests. However, nested variant of urothelial carcinoma with tubule formation can also resemble nephrogenic adenoma, where immunohistochemical positivity for PAX8 has been used to establish the diagnosis of nephrogenic adenoma. Following anecdotal examples of PAX8 positive nested variant of urothelial carcinoma, we formally evaluated 23 cases of nested variant of urothelial carcinoma from 2011 to 2018. Cases were collected from our institution and evaluated for their architectural pattern and PAX8 expression. Except for 1 case from the renal pelvis, cases were located in the bladder. The majority (14/23 [61%]) showed solid nests with at least focal tubular differentiation. PAX8 immunoreactivity was strong (3+) in 7 (30%), moderate (2+) in 6 (26%), and negative in 10 (44%) cases. Four (57%) of the cases with strong expression and 3 (50%) of those with moderate staining showed diffuse immunoreactivity. Moderate-strong immunoreactivity was seen in 4/6 (66.7%) cases with solid nests, 8/14 (57.1%) with solid nests and tubules, and 1/3 (33.3%) with large nests. In conclusion, PAX8 can be positive in a significant proportion of nested variant of urothelial carcinoma cases, and recognition of this finding is important to avoid misdiagnosis of nested variant of urothelial carcinoma as nephrogenic adenoma based on PAX8 expression, particularly in cases with tubular differentiation and limited sampling.
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Biomarcadores de Tumor/análisis , Carcinoma/química , Inmunohistoquímica , Neoplasias Renales/química , Factor de Transcripción PAX8/análisis , Neoplasias de la Vejiga Urinaria/química , Urotelio/química , Adulto , Anciano , Carcinoma/patología , Diferenciación Celular , Diagnóstico Diferencial , Femenino , Humanos , Neoplasias Renales/patología , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados , Estudios Retrospectivos , Neoplasias de la Vejiga Urinaria/patología , Urotelio/patologíaRESUMEN
BACKGROUND: Thyroid fine-needle aspiration (FNA) plays a key role in triaging thyroid nodules. Yet many cases are assigned to indeterminate categories. The new category "noninvasive follicular thyroid neoplasm with papillary-like features" (NIFTP) complicates thyroid cytology. Digital image-derived nuclear measurements might objectively distinguish papillary thyroid carcinoma (PTC) from benign nodules and NIFTP. METHODS: All thyroid FNAs from 2012 to 2016 of atypia of undetermined significance (A; n = 8) and suspicious for malignancy (S; n = 2) with sufficient cellularity and surgical follow-up, all FNAs preceding NIFTP (n = 6), and a random sample of PTC (n = 9) and benign (n = 10) cytology were studied. A modified Giemsa-stained slide from each case was scanned using the Aperio imaging system, and long (dl ) and short (ds )-axis diameters were measured for 125 nuclei per case. Nuclear area and elongation were calculated. RESULTS: Nuclear area was larger in PTC (mean, 77.2 µm2 [range, 70.6-86.0 µm2 ]) than benign (mean, 43.3 µm2 [range 38.2-52.2 µm2 ]) (P < .001). Nuclear areas from indeterminate FNAs segregated according to final histology (A/S PTC mean 72.7 µm2 , A/S benign mean 53.7 µm2 ; P = 0.004), and were not significantly different from definitive FNAs of the same diagnosis. NIFTP nuclear area was smaller than PTC (mean, 54.8 µm2 [range, 46.7-66.1 µm2 ]; P < .001). Nuclear elongation showed similar results, but with greater group overlap. CONCLUSION: Nuclear area and elongation can be calculated using a commercial digital imager; both correlate with the final surgical pathology diagnosis of PTC versus benign, including NIFTP. Area provides greater resolution than elongation. This technique could be used to resolve indeterminate cytology in which PTC is considered.
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Adenocarcinoma Folicular/diagnóstico , Procesamiento de Imagen Asistido por Computador , Cáncer Papilar Tiroideo/diagnóstico , Neoplasias de la Tiroides/diagnóstico , Nódulo Tiroideo/diagnóstico , Adenocarcinoma Folicular/patología , Adenocarcinoma Folicular/cirugía , Biopsia con Aguja Fina/métodos , Núcleo Celular/patología , Humanos , Estudios Retrospectivos , Programas Informáticos , Cáncer Papilar Tiroideo/patología , Cáncer Papilar Tiroideo/cirugía , Glándula Tiroides/citología , Glándula Tiroides/patología , Glándula Tiroides/cirugía , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/cirugía , Nódulo Tiroideo/patología , Nódulo Tiroideo/cirugía , TiroidectomíaRESUMEN
INTRODUCTION: An international panel recently recommended reclassification of non-invasive follicular variant of papillary thyroid carcinoma (PTC) to non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). NIFTPs have little or no risk of recurrence and can be treated with lobectomy alone. Preoperative distinction of NIFTP from PTC will help avoid overtreatment. MATERIALS AND METHODS: All thyroid tumors with a histologic diagnosis of PTC and preceding diagnostic cytology (n = 299) over a 5-year period were identified. Cases meeting criteria for NIFTP were reclassified as such. All NIFTP cases with available cytology (n = 6) and a similar number of randomly selected invasive follicular variant of papillary thyroid carcinoma (IFVPTC; n = 9) and classic PTC (cPTC, n = 11) were evaluated for 18 cytologic features. RESULTS: A total of 35 (12%) lesions were reclassified as NIFTP, 194 (65%) were cPTC, and 70 (23%) were IFVPTC. The NIFTPs had a preceding cytologic interpretation of benign (31%), atypia of undetermined significance (34%), follicular neoplasm (9%), suspicious for malignancy (12%), or malignant (14%). Cytologically, NIFTP was distinguished from cPTC by absence of any architectural features in all 6 cases, and by absence of pseudoinclusions (P < 0.001) and multinucleated giant cells (P = 0.027) in nearly all. Nuclear pseudoinclusions (P = 0.001), marginal micronucleoli (P = 0.018), irregular branching sheets (P = 0.025), and linear arrangement (P = 0.025) favored IFVPTC over NIFTP. CONCLUSIONS: NIFTPs were originally assigned to a variety of cytologic categories. There are several cytologic differences between NIFTP and cPTC or IFVPTC. Our findings support restricting the definitive diagnosis of PTC to cases with architectural features of PTC and/or intranuclear pseudoinclusions.
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Adenocarcinoma Folicular/patología , Carcinoma Papilar Folicular/patología , Cáncer Papilar Tiroideo/patología , Neoplasias de la Tiroides/patología , Adenocarcinoma Folicular/clasificación , Carcinoma Papilar Folicular/clasificación , Diagnóstico Diferencial , Humanos , Cáncer Papilar Tiroideo/clasificación , Neoplasias de la Tiroides/clasificaciónRESUMEN
The microtubule-stabilizing agent docetaxel in combination with gemcitabine represents one of the most effective regimens against the aggressive gynecologic tumor leiomyosarcoma (LMS). Upregulation of class III ß-tubulin has previously been shown to confer taxane resistance in a variety of human cancers. Prostaglandin E2 receptor EP4 is linked to progression of a variety of human cancers and may represent a novel target for tumor inhibition in LMS. We evaluated the hypotheses that EP4 and class III ß-tubulin have increased expression in LMS in comparison to normal myometrium or benign tumors and that expression of class III ß-tubulin correlates with resistance to taxanes and poor clinical outcome. Gene expression was examined using TCGA data and correlated with clinicopathologic outcome which demonstrated that class III ß-tubulin is more highly expressed in more aggressive sarcomas with EP4 being widely expressed in all subtypes of sarcoma. Immunohistochemistry for EP4 and class III ß-tubulin was performed on patients with LMS, leiomyomatosis/STUMP, leiomyoma, and normal myometrium. Expression of EP4 and class III ß-tubulin were characterized for cell lines SK-UT-1, SK-UT-1B, and PHM-41 and these cell lines were treated with docetaxel alone and in combination with EP4 inhibitors. In taxane-resistant cell lines that overexpress class III ß-tubulin and EP4, treatment with EP4 inhibitor resulted in at least 2-fold sensitization to docetaxel. Expression of class III ß-tubulin and EP4 in LMS may identify patients at risk of resistance to standard chemotherapies and candidates for augmentation of therapy through EP4 inhibition.
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We report the case of a 49-year-old white man with a chromophobe renal cell carcinoma associated with sarcomatoid differentiation, an uncommon yet an aggressive form of dedifferentiated renal cell carcinoma. In opposite to the conventional renal cell carcinoma, which may not always demonstrate avid FDG activity, the sarcomatoid differentiated chromophobe renal cell carcinoma shows intense FDG uptake on PET. This case highlights the role of FDG PET/CT in staging and restaging this type of rare renal cell carcinoma.