RhoA downregulation in the murine intestinal epithelium results in chronic Wnt activation and increased tumorigenesis.

Rho GTPases are molecular switches regulating multiple cellular processes. To investigate the role of RhoA in normal intestinal physiology, we used a conditional mouse model overexpressing a dominant negative RhoA mutant (RhoAT19N) in the intestinal epithelium. Although RhoA inhibition did not cause an overt phenotype, increased levels of nuclear ß-catenin were observed in the small intestinal epithelium of RhoAT19N mice, and the overexpression of multiple Wnt target genes revealed a chronic activation of Wnt signaling. Elevated Wnt signaling in RhoAT19N mice and intestinal organoids did not affect the proliferation of intestinal epithelial cells but significantly interfered with their differentiation. Importantly, 17-month-old RhoAT19N mice showed a significant increase in the number of spontaneous intestinal tumors. Altogether, our results indicate that RhoA regulates the differentiation of intestinal epithelial cells and inhibits tumor initiation, likely through the control of Wnt signaling, a key regulator of proliferation and differentiation in the intestine.

Expert-based collaborative analysis of the situation and prospects of biomarker test implementation in oncology in Spain.

PURPOSE: Biomarkers as screening for precision medicine is a fundamental step. The purpose of this article is twofold. First, to highlight the existing barriers in the implementation of Precision Medicine in Spain, with a special emphasis on barriers in access to the determination of biomarkers. Second, to provide a Roadmap that can help implement Precision Medicine equitably at the national level and optimize the use of biomarkers. METHODS: A systematic review of literature (SRL) and a focus group (FG) with multidisciplinary experts has been carried out in 2023. Participants were contacted individually, and discourse analysis was processed anonymously. RESULTS: We carried out a quantitative (SRL) and a qualitative approach (FG). The discourse analysis and roadmap were sent individually to each expert for approval. CONCLUSIONS: The potential of Precision Medicine has not been fulfilled in Spain. While several regional initiatives are in place, a national plan or strategy around Precision Medicine and use of biomarkers is lacking. In a general context of rapid progress at a global and European level, including the 2021 Europe's Beating Cancer Plan, it is time to define and implement a National Plan to make the promise come true. While some comparable countries within Europe - such as the UK or France - are mature enough to adopt such strategies, in Spain there is still a long way to go. We consider that the different strands of work outlined in the Roadmap can be used as basis for such purpose.

Weakly Supervised Deep Learning Predicts Immunotherapy Response in Solid Tumors Based on PD-L1 Expression.

Programmed death-ligand 1 (PD-L1) IHC is the most commonly used biomarker for immunotherapy response. However, quantification of PD-L1 status in pathology slides is challenging. Neither manual quantification nor a computer-based mimicking of manual readouts is perfectly reproducible, and the predictive performance of both approaches regarding immunotherapy response is limited. In this study, we developed a deep learning (DL) method to predict PD-L1 status directly from raw IHC image data, without explicit intermediary steps such as cell detection or pigment quantification. We trained the weakly supervised model on PD-L1-stained slides from the non-small cell lung cancer (NSCLC)-Memorial Sloan Kettering (MSK) cohort (N = 233) and validated it on the pan-cancer-Vall d'Hebron Institute of Oncology (VHIO) cohort (N = 108). We also investigated the performance of the model to predict response to immune checkpoint inhibitors (ICI) in terms of progression-free survival. In the pan-cancer-VHIO cohort, the performance was compared with tumor proportion score (TPS) and combined positive score (CPS). The DL model showed good performance in predicting PD-L1 expression (TPS ≥ 1%) in both NSCLC-MSK and pan-cancer-VHIO cohort (AUC 0.88 ± 0.06 and 0.80 ± 0.03, respectively). The predicted PD-L1 status showed an improved association with response to ICIs [HR: 1.5 (95% confidence interval: 1-2.3), P = 0.049] compared with TPS [HR: 1.4 (0.96-2.2), P = 0.082] and CPS [HR: 1.2 (0.79-1.9), P = 0.386]. Notably, our explainability analysis showed that the model does not just look at the amount of brown pigment in the IHC slides, but also considers morphologic factors such as lymphocyte conglomerates. Overall, end-to-end weakly supervised DL shows potential for improving patient stratification for cancer immunotherapy by analyzing PD-L1 IHC, holistically integrating morphology and PD-L1 staining intensity. SIGNIFICANCE: The weakly supervised DL model to predict PD-L1 status from raw IHC data, integrating tumor staining intensity and morphology, enables enhanced patient stratification in cancer immunotherapy compared with traditional pathologist assessment.

Platelet Analysis in the Thrombus Plus Serum BNP for Detecting Clot-Related Atrial Fibrillation. Results From the ITACAT Multicentric Registry.

Occult atrial fibrillation (AF) is a common cause of cryptogenic stroke. This study aimed to investigate the utility of surrogate markers within the clot (clot markers), in combination with serum biomarkers, to identify AF-associated clots in patients who underwent mechanical thrombectomy. Each retrieved thrombus was analyzed to identify fibrin, red blood cells, platelets - CD61 staining (PLT) and T-CD4 lymphocyte/macrophage/monocyte (CD4) profile. Serum biomarkers such as D-dimer, lipoprotein (A), and brain natriuretic peptide (BNP) were also assessed in the acute phase of the stroke. Patients with stroke-related AF and large artery atherosclerosis (LAA) stroke were compared by matched case-control design to identify markers associated with AF clot profile. The predictive abilities of clot markers and serum biomarkers to detect AF clot were tested in patients with cryptogenic stroke. In patients with AF clot, the PLT percentage was higher (66.64% vs. 55.43%, OR = 1.03); CD4 percentage was lower (3.84% vs. 7.95%, OR = 0.95); and BNP marker was higher (2114 pg/ml vs. 276 pg/ml, OR = 1.04) compared to LAA clot. PLT was independently associated to AF-clot (OR, 1.04) but demonstrated moderate ability to identify AF-clot cases (C-test 0.668, p = 0.018). The combination of PLT with BNP significantly improved AF-clot prediction (C-test 0.847, p < 0.001). The clot composition of patients with cryptogenic stroke and AF detection showed four-fold higher PLT and BNP pattern of risk than patients with cryptogenic stroke without AF detection (38.5% vs. 8.7%) (OR = 1.40). Integrating intra-thrombus platelet with serum BNP offers a promising approach for detecting AF-associated clots in patients with cryptogenic stroke.

Wall enhancement as a biomarker of intracranial aneurysm instability: a histo-radiological study.

BACKGROUND: The aim of this is to explore the histological basis of vessel wall enhancement (WE) on magnetic resonance imaging (MRI), which is a strong radiological biomarker of aneurysmal prone to rupture compared to other classical risk predictors (e.g., PHASES score, size, morphology). METHODS: A prospective observational study was performed including all consecutive patients presenting with a saccular intracranial aneurysm at Vall d'Hebron University Hospital between October 2017 and May 2019. The patients underwent high-resolution 3 T MRI, and their aneurysms were classified into asymptomatic, symptomatic, and ruptured. A histological and immunohistochemical study was performed in a subgroup of patients (n = 20, of which 15 presented with WE). Multiple regression analyses were performed to identify predictors of rupture and aneurysm symptoms. RESULTS: A total of 132 patients were enrolled in the study. WE was present in 36.5% of aneurysms: 22.9% asymptomatic, 76.9% symptomatic, and 100% ruptured. Immunohistochemical markers associated with WE were CD3 T cell receptor (p = 0.05) and CD45 leukocyte common antigen (p = 0.05). Moreover, WE is an independent predictor of symptomatic and ruptured aneurysms (p < 0.001). CONCLUSIONS: Aneurysms with WE present multiple histopathological changes that may contribute to wall disruption and represent the pathophysiological basis of radiological WE. Moreover, WE is an independent diagnostic predictor of aneurysm symptoms and rupture.

Hybrid neurofibroma/schwannoma of the orbit / Tumor híbrido neurofibroma/schwannoma de la órbita

Hybrid neurofibroma/schwannoma is a rare variant of hybrid peripheral nerve sheath tumours (HPNST). A Medline search up to December 2021 identified only six cases of this tumour in the orbit. We report the case of a 78-year-old man who presented with left exophthalmos. Computed tomography showed a left intraconal orbital mass. The clinico-radiological diagnosis was consistent with an intraconal cavernous angioma. Orbitotomy was performed, obtaining an 18×16×11mm mass. Two different morphologies were seen microscopically, diagnostic of hybrid neurofibroma/schwannoma. HPNSTs of the orbit are uncommon and most reported cases showed a hybrid neurofibroma/schwannoma morphology. Hybrid neurofibroma/schwannomas have been associated with neurofibromatosis and schwannomatosis. Local recurrences have been reported. The correct identification of these tumours is important due to their potential use as a syndromic marker.(AU)

El tumor híbrido neurofibroma/schwannoma es una lesión rara incluida dentro de tumores híbridos de la vaina del nervio periférico. Mediante revisión bibliográfica en Medline hasta diciembre de 2021 se identificó solo seis casos de este tumor en la órbita. Presentamos el caso de un varón de 78 años que consultó por exoftalmos izquierdo. La tomografía computarizada mostró una masa orbitaria intraconal izquierda. El diagnóstico clínico-radiológico fue compatible con angioma cavernoso intraconal. Se realizó una orbitotomía, obteniendo una masa de 18×16×11mm. Microscópicamente, el tumor mostró dos morfologías diferentes compatibles con tumor híbrido neurofibroma/schwannoma. Los tumores híbridos de la vaina del nervio periférico de la órbita son poco comunes. La mayoría de los casos informados muestran una morfología híbrida de neurofibroma/schwannoma. El tumor híbrido neurofibroma/schwannoma se ha asociado con neurofibromatosis y schwannomatosis. Se han reportado recurrencias locales. La correcta identificación de estos tumores es relevante debido a su potencial uso como marcador sindrómico.(AU)

Granulocytes-Rich Thrombi in Cerebral Large Vessel Occlusion Are Associated with Increased Stiffness and Poorer Revascularization Outcomes.

We aim to identify a profile of intracranial thrombus resistant to recanalization by mechanical thrombectomy (MT) in acute stroke treatment. The first extracted clot of each MT was analyzed by flow cytometry obtaining the composition of the main leukocyte populations: granulocytes, monocytes, and lymphocytes. Demographics, reperfusion treatment, and grade of recanalization were registered. MT failure (MTF) was defined as final thrombolysis in cerebral infarction score IIa or lower and/or need of permanent intracranial stenting as a rescue therapy. To explore the relationship between stiffness of intracranial clots and cellular composition, unconfined compression tests were performed in other cohorts of cases. Thrombi obtained in 225 patients were analyzed. MTF were observed in 30 cases (13%). MTF was associated with atherosclerosis etiology (33.3% vs. 15.9%; p = 0.021) and higher number of passes (3 vs. 2; p < 0.001). Clot analysis of MTF showed higher percentage of granulocytes [82.46 vs. 68.90% p < 0.001] and lower percentage of monocytes [9.18% vs.17.34%, p < 0.001] in comparison to successful MT cases. The proportion of clot granulocytes (aOR 1.07; 95% CI 1.01-1.14) remained an independent marker of MTF. Among thirty-eight clots mechanically tested, there was a positive correlation between granulocyte proportion and thrombi stiffness (Pearson's r = 0.35, p = 0.032), with a median clot stiffness of 30.2 (IQR, 18.9-42.7) kPa. Granulocytes-rich thrombi are harder to capture by mechanical thrombectomy due to increased stiffness, so a proportion of intracranial granulocytes might be useful to guide personalized endovascular procedures in acute stroke treatment.

Hybrid neurofibroma/schwannoma of the orbit.

Hybrid neurofibroma/schwannoma is a rare variant of hybrid peripheral nerve sheath tumours (HPNST). A Medline search up to December 2021 identified only six cases of this tumour in the orbit. We report the case of a 78-year-old man who presented with left exophthalmos. Computed tomography showed a left intraconal orbital mass. The clinico-radiological diagnosis was consistent with an intraconal cavernous angioma. Orbitotomy was performed, obtaining an 18×16×11mm mass. Two different morphologies were seen microscopically, diagnostic of hybrid neurofibroma/schwannoma. HPNSTs of the orbit are uncommon and most reported cases showed a hybrid neurofibroma/schwannoma morphology. Hybrid neurofibroma/schwannomas have been associated with neurofibromatosis and schwannomatosis. Local recurrences have been reported. The correct identification of these tumours is important due to their potential use as a syndromic marker.

Integrating digital pathology with transcriptomic and epigenomic tools for predicting metastatic uterine tumor aggressiveness.

The incidence of new cancer cases is expected to increase significantly in the future, posing a worldwide problem. In this regard, precision oncology and its diagnostic tools are essential for developing personalized cancer treatments. Digital pathology (DP) is a particularly key strategy to study the interactions of tumor cells and the tumor microenvironment (TME), which play a crucial role in tumor initiation, progression and metastasis. The purpose of this study was to integrate data on the digital patterns of reticulin fiber scaffolding and the immune cell infiltrate, transcriptomic and epigenetic profiles in aggressive uterine adenocarcinoma (uADC), uterine leiomyosarcoma (uLMS) and their respective lung metastases, with the aim of obtaining key TME biomarkers that can help improve metastatic prediction and shed light on potential therapeutic targets. Automatized algorithms were used to analyze reticulin fiber architecture and immune infiltration in colocalized regions of interest (ROIs) of 133 invasive tumor front (ITF), 89 tumor niches and 70 target tissues in a total of six paired samples of uADC and nine of uLMS. Microdissected tissue from the ITF was employed for transcriptomic and epigenetic studies in primary and metastatic tumors. Reticulin fiber scaffolding was characterized by a large and loose reticular fiber network in uADC, while dense bundles were found in uLMS. Notably, more similarities between reticulin fibers were observed in paired uLMS then paired uADCs. Transcriptomic and multiplex immunofluorescence-based immune profiling showed a higher abundance of T and B cells in primary tumor and in metastatic uADC than uLMS. Moreover, the epigenetic signature of paired samples in uADCs showed more differences than paired samples in uLMS. Some epigenetic variation was also found between the ITF of metastatic uADC and uLMS. Altogether, our data suggest a correlation between morphological and molecular changes at the ITF and the degree of aggressiveness. The use of DP tools for characterizing reticulin scaffolding and immune cell infiltration at the ITF in paired samples together with information provided by omics analyses in a large cohort will hopefully help validate novel biomarkers of tumor aggressiveness, develop new drugs and improve patient quality of life in a much more efficient way.

Clearance of ctDNA in triple-negative and HER2-positive breast cancer patients during neoadjuvant treatment is correlated with pathologic complete response.

Background: Although the standard of care is to perform surgery of primary breast cancer (BC) after neoadjuvant chemotherapy (NAC), for certain patients achieving clinical complete response (cCR) and pathologic complete response (pCR), omission of surgical treatment may be an option. Levels of circulating tumor DNA (ctDNA) during and after therapy could identify patients achieving minimal residual disease. In this study, we evaluated whether ctDNA clearance during NAC could be a correlate to effective response in human epidermal growth factor receptor 2 positive (HER2+) and triple-negative (TN) BC patients. Methods: A prospective study was conducted to identify patient-specific PIK3CA and TP53 mutations in tissue using next-generation sequencing, which could then be used to track the presence/absence of mutations prior to, during, and following NAC using Sysmex SafeSEQ technology. All patients underwent a surgical excision after NAC, and pCR was assessed. Results: A total of 29 TN and HER2+ BC patients were examined and 20 that carried mutations in the PIK3CA and/or TP53 genes were recruited. Overall, 19 of these 20 patients harbored at least one tumor-specific mutation in their plasma at baseline. After NAC, 15 patients (75.0%) achieved pCR according to the histopathologic evaluation of the surgical specimen, and 15 patients (75.0%) had a cCR; 18 of 20 patients (90.0%) had concordant pCR and cCR. The status of 'no mutation detected' (NMD) following NAC in cCR patients correctly identified the pCR in 14 of 15 patients (93.33%), as well as correctly ruled out pCR in three patients, with an accuracy of 89.47%. During the 12-month follow-up after surgery, 40 plasma samples collected from 15 patients all showed no detectable ctDNA (NMD), and no patient recurred. Conclusion: These findings prompt further research of the value of ctDNA for non-invasive prediction of clinical/pathological response, raising the possibility of sparing surgery following NAC in selected BC patients.

Myosin Vb as a tumor suppressor gene in intestinal cancer.

Colorectal cancer causes >900,000 deaths every year and a deeper understanding of the molecular mechanisms underlying this disease will contribute to improve its clinical management and survival. Myosin Vb (MYO5B) regulates intracellular vesicle trafficking, and inactivation of this myosin disrupts the polarization and differentiation of intestinal epithelial cells causing microvillous inclusion disease (MVID), a rare congenital disorder characterized by intractable life-threatening diarrhea. Here, we show that the loss Myosin Vb interfered with the differentiation/polarization of colorectal cancer cells. Although modulation of Myosin Vb expression did not affect the proliferation of colon cancer cells, MYO5B inactivation increased their migration, invasion, and metastatic potential. Moreover, Myo5b inactivation in an intestine-specific knockout mouse model caused a >15-fold increase in the number of azoxymethane-initiated small intestinal tumors. Consistently, reduced expression of Myosin Vb in a cohort of 155 primary colorectal tumors was associated with shorter patient survival. In conclusion, we show here that loss of Myosin Vb reduces polarization/differentiation of colon cancer cells while enhancing their metastatic potential, demonstrating a tumor suppressor function for this myosin. Moreover, reduced expression of Myosin Vb in primary tumors identifies a subset of poor prognosis colorectal cancer patients that could benefit from more aggressive therapeutic regimens.

pTINCR microprotein promotes epithelial differentiation and suppresses tumor growth through CDC42 SUMOylation and activation.

The human transcriptome contains thousands of small open reading frames (sORFs) that encode microproteins whose functions remain largely unexplored. Here, we show that TINCR lncRNA encodes pTINCR, an evolutionary conserved ubiquitin-like protein (UBL) expressed in many epithelia and upregulated upon differentiation and under cellular stress. By gain- and loss-of-function studies, we demonstrate that pTINCR is a key inducer of epithelial differentiation in vitro and in vivo. Interestingly, low expression of TINCR associates with worse prognosis in several epithelial cancers, and pTINCR overexpression reduces malignancy in patient-derived xenografts. At the molecular level, pTINCR binds to SUMO through its SUMO interacting motif (SIM) and to CDC42, a Rho-GTPase critical for actin cytoskeleton remodeling and epithelial differentiation. Moreover, pTINCR increases CDC42 SUMOylation and promotes its activation, triggering a pro-differentiation cascade. Our findings suggest that the microproteome is a source of new regulators of cell identity relevant for cancer.

[Twin gestation with complete hydatidiform mole and a coexisting live fetus: A case report and review of the literature]. / Embarazo gemelar con mola hidatiforme completa y feto vivo asociado: reporte de un caso y revisión bibliográfica.

Twin pregnancies with complete hydatidiform mole and coexisting live fetus are very rare, with only about 300 reported cases. This type of pregnancy is considered a high obstetric risk due to the possibility of severe maternal-fetal complications. Although the clinical and ultrasound findings can be highly suggestive of this type of pregnancy, the definitive diagnosis is usually reached by histopathological examination. The differential diagnosis usually includes partial hydatidiform mole and hydropic pregnancies, which can present similar findings in specimens from the first trimester of pregnancy and thus it is important to interpret correctly the differentiating features. The use of immunohistochemistry for p57 can prove very useful, although some cases show an aberrant expression. We present a case of a twin pregnancy with complete hydatidiform mole associated with a live fetus, with magnetic resonance imaging and ultrasound for radiopathological correlation. We discuss the differential diagnosis and the utility of p57 immunohistochemistry.

ERK5 Is a Major Determinant of Chemical Sarcomagenesis: Implications in Human Pathology.

Sarcomas are a heterogeneous group of tumors in which the role of ERK5 is poorly studied. To clarify the role of this MAPK in sarcomatous pathology, we used a murine 3-methyl-cholanthrene (3MC)-induced sarcoma model. Our data show that 3MC induces pleomorphic sarcomas with muscle differentiation, showing an increased expression of ERK5. Indeed, this upregulation was also observed in human sarcomas of muscular origin, such as leiomyosarcoma or rhabdomyosarcoma. Moreover, in cell lines derived from these 3MC-induced tumors, abrogation of Mapk7 expression by using specific shRNAs decreased in vitro growth and colony-forming capacity and led to a marked loss of tumor growth in vivo. In fact, transcriptomic profiling in ERK5 abrogated cell lines by RNAseq showed a deregulated gene expression pattern for key biological processes such as angiogenesis, migration, motility, etc., correlating with a better prognostic in human pathology. Finally, among the various differentially expressed genes, Klf2 is a key mediator of the biological effects of ERK5 as indicated by its specific interference, demonstrating that the ERK5-KLF2 axis is an important determinant of sarcoma biology that should be further studied in human pathology.

[Lipoblastoma-like tumor of the vulva: A case report and review of the literature]. / Tumor vulvar similar a lipoblastoma: descripción de un nuevo caso y revisión de la literatura.

Lipoblastoma-like tumor of the vulva (LBLTV) was first described as a benign mesenchymal neoplasia; it was not recognized as a separate diagnosis in the 2013 WHO classification of soft-tissue tumors. To date, only 19 cases have been reported. LBLTV differential diagnosis includes other tumors of the vulvoperineal region and tumors with adipocytic differentiation, most of which are benign and thus a misdiagnosis has few clinical consequences. However, LBLTV may also mimic some aggressive lipomatous neoplasms. We describe a case of LBLTV in a 28 year-old woman and review the literature.

Overcoming Paradoxical Kinase Priming by a Novel MNK1 Inhibitor.

Targeting the kinases MNK1 and MNK2 has emerged as a valuable strategy in oncology. However, most of the advanced inhibitors are acting in an adenosine triphosphate (ATP)-competitive mode, precluding the evaluation of different binding modes in preclinical settings. Using rational design, we identified and validated the 4,6-diaryl-pyrazolo[3,4-b]pyridin-3-amine scaffold as the core for MNK inhibitors. Signaling pathway analysis confirmed a direct effect of the hit compound EB1 on MNKs, and in line with the reported function of these kinases, EB1 only affects the growth of tumor but not normal cells. Molecular modeling revealed the binding of EB1 to the inactive conformation of MNK1 and the interaction with the specific DFD motif. This novel mode of action appears to be superior to the ATP-competitive inhibitors, which render the protein in a pseudo-active state. Overcoming this paradoxical activation of MNKs by EB1 represents therefore a promising starting point for the development of a novel generation of MNK inhibitors.

DigiPatICS: Digital Pathology Transformation of the Catalan Health Institute Network of 8 Hospitals-Planification, Implementation, and Preliminary Results.

Complete digital pathology transformation for primary histopathological diagnosis is a challenging yet rewarding endeavor. Its advantages are clear with more efficient workflows, but there are many technical and functional difficulties to be faced. The Catalan Health Institute (ICS) has started its DigiPatICS project, aiming to deploy digital pathology in an integrative, holistic, and comprehensive way within a network of 8 hospitals, over 168 pathologists, and over 1 million slides each year. We describe the bidding process and the careful planning that was required, followed by swift implementation in stages. The purpose of the DigiPatICS project is to increase patient safety and quality of care, improving diagnosis and the efficiency of processes in the pathological anatomy departments of the ICS through process improvement, digital pathology, and artificial intelligence tools.

La necesidad de la coordinación técnica en los servicios de Anatomía Patológica. Documento de posicionamiento de la Sociedad Española de Anatomía Patológica / The Spanish Society of Pathology's policy document concerning the necessity for technical coordination in Pathology departments

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Tumor vulvar similar a lipoblastoma: descripción de un nuevo caso y revisión de la literatura / Lipoblastoma-like tumor of the vulva: A case report and review of the literature

El tumor vulvar similar a lipoblastoma (LBLTV) fue descrito inicialmente como una neoplasia mesenquimal benigna. Desde entonces, se han reportado únicamente 19 casos. Además, esta entidad no ha sido reconocida aún como diagnóstico separado en la clasificación de la OMS (2013) de los tumores de tejido blando. El diagnóstico diferencial de LBLTV incluye otros tumores de la región vulvoperineal, así como tumores con diferenciación adipocítica, la mayoría de ellos benignos. Por tanto, un diagnóstico erróneo aporta pocas consecuencias clínicas. Sin embargo, LBLTV puede imitar también algunas neoplasias lipomatosas agresivas. Describimos aquí un nuevo caso de LBLTV en una mujer de 28 años, así como una revisión de la literatura.(AU)

Lipoblastoma-like tumor of the vulva (LBLTV) was first described as a benign mesenchymal neoplasia; it was not recognized as a separate diagnosis in the 2013 WHO classification of soft-tissue tumors. To date, only 19 cases have been reported. LBLTV differential diagnosis includes other tumors of the vulvoperineal region and tumors with adipocytic differentiation, most of which are benign and thus a misdiagnosis has few clinical consequences. However, LBLTV may also mimic some aggressive lipomatous neoplasms. We describe a case of LBLTV in a 28 year-old woman and review the literature.(AU)