Ultrasound as a Valuable Imaging Modality in Sclerosing Lymphocytic Lobulitis: Imaging Features Based on a Retrospective Cohort Analysis of 51 Cases.

PURPOSE: Sclerosing lymphocytic lobulitis (SLL) is a rare benign breast condition usually associated with diabetes mellitus and whose imaging features have been assessed in few studies, limiting the adoption of diagnostic guidelines. We aimed to identify the main morphological features associated with SLL on imaging examinations (mainly ultrasound and mammography) and to retrospectively evaluate the role that each method played in the diagnostic workup (detection and indication for biopsy). METHODS: A retrospective study was conducted in a high-volume single center, encompassing 51 consecutive patients (100% female; 26-78 y; 43.7 ± 15.5 y) with histopathologically proven SLL (59 lesions; 0.5-6.1 cm). RESULTS: Most lesions (31/59; 53%) were found in asymptomatic individuals. Ultrasound detected 91.1% (51 out of 56 lesions assessed by this modality), of which 94.1% were non-circumscribed masses (BI-RADS® 4). Mammography detected 41.6% (15 out of 36 lesions assessed by this modality), with a predominance (80%) of non-calcified ones (masses, asymmetries and distortion). Two-year follow-up was achieved in 29 lesions (49%), showing complete remission (45%) or stability (41%) in most cases. CONCLUSIONS: Most lesions in this retrospective sample have been detected by means of ultrasound and had their need for biopsy indicated by this modality. Female diabetic patients younger than 40 years presenting with a palpable lesion and a non-circumscribed mass on ultrasound could be submitted to core biopsy; histopathologic findings suggestive of SLL should be considered concordant in this scenario, with subsequent conservative treatment.

Cavernous Hemangioma Between the Elastomer and Fibrous Capsule of a Breast Implant.

Hemangiomas are described in many locations, but breast hemangioma (BH) is rare, accounting for only 0.4% of all breast tumors. These tumors are difficult to diagnose preoperatively using conventional imaging modalities because they lack pathognomonic characteristics. Mammographic and sonographic appearances of BH were described in just a few case reports, and breast implant-related hemangiomas are even rarer. We report a case of the tumor arising in an atypical location-between the elastomer and fibrous capsule of a breast implant.Level of Evidence V This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Prognostication of vulvar cancer based on p14ARF status: molecular assessment of transcript and protein.

PURPOSE: This study was designed to determine the prognostic role of p14ARF in vulvar squamous cell carcinoma (VSCC). METHODS: Immunohistochemistry for p14ARF and p53 and fluorescent in situ hybridization (FISH) for TP53 were performed in 139 cases of VSCC. Human papillomavirus (HPV) genotyping by hybridization was employed in 100 cases. qRT-PCR for p14ARF and p53 transcript assessment was performed in 16 cases. All results were correlated with clinicopathological variables. RESULTS: Immunohistochemistry analysis showed p14ARF and p53 positivity in 16.4% and 53% cases respectively. Positive p14ARF expression was significantly associated with the following variables: shorter cancer-specific survival (P=0.04) and shorter disease-free survival (P=0.02), presence of perineural invasion (P=0.037), vascular invasion (P=0.047), and node metastasis (P=0.031). Also, p14ARF-positive HPV-negative cases had the shortest cancer-specific survival (P=0.03) and disease-free survival (P=0.04). HPV infection was detected in 32.8% of the cases; HPV16 was the most prevalent type. Viral infection was more common in poorly differentiated tumors (P=0.032). qRT-PCR demonstrated that CDKN2A (p14ARF) had higher expression in tumor samples compared with paired noncancerous samples (P<0.001). The opposite relationship was seen in TP53 expression evaluation (P<0.001). FISH demonstrated 4 cases with deleted TP53 (6.3%). CONCLUSIONS: p14ARF represents an important marker of poor prognosis in VSCC. p53 and HPV infection did not show any prognostic importance. Further clinical trials concerning p14ARF positivity may result in important contributions due to its relationship with poor outcome. Mainly due to the relationship of p14ARF with lymph node metastasis, the immunohistochemistry evaluation of this marker may help to identify a subset of patients more suitable to less radical procedures.

Cell cycle suppressor proteins are not related to HPV status or clinical outcome in patients with vulvar carcinoma.

Interactions between the cyclin-dependent kinase inhibitors (CDKI) and human papillomavirus (HPV) infection in the pathogenesis of vulvar carcinoma are still incomplete. This study aimed to evaluate the prognostic relevance of these proteins in vulvar cancer. One hundred and thirty-nine patient specimens assembled in a tissue microarray were evaluated for p16, p21, p27, and pRb by immunohistochemistry. HPV status was assessed by a linear array HPV genotyping test. In 16 cases with available frozen tumor, quantitative real-time reverse transcriptase-polymerase chain reaction for CDKN2A(p16), CDKN1A, and Rb was performed. Protein expression was considered positive in 40 patients for p16, 35 for p21, 28 for p27, and 19 for pRb. HPV was positive in 43 of the 105 evaluable cases. Expression of CDKIs and pRb, with the exception of p16, seem to be linked to the early phases of vulvar carcinogenesis. Although p16 and p21 protein expression was associated with early stages of disease, no prognostic significance was found when analyzing CDKI proteins or detecting HPV status, limiting their clinical usage. No association was observed between expression of CDKI proteins and HPV status, suggesting that in spite of this association found in cervical cancer, this seems not to be valid for vulvar carcinoma.

Role of Fos-related antigen 1 in the progression and prognosis of ductal breast carcinoma.

AIMS: Fos-related antigen 1 (Fra-1) is a member of the activator protein 1 (AP-1) transcription factor family. Our objective was to evaluate the role of Fra-1 expression in breast carcinoma progression and prognosis. METHODS AND RESULTS: Fra-1 expression was investigated by immunohistochemistry in two tissue microarrays containing, respectively, 85 ductal carcinoma in situ (DCIS) and 771 invasive ductal carcinoma (IDC) samples. Staining was observed in the nucleus and cytoplasm of the carcinomas, but only nuclear staining was considered to be positive. Fibroblasts associated with IDC were also Fra-1-positive. The frequency of Fra-1 positivity in IDC (22.8%) was lower than that in DCIS (42.2%). No association was found between Fra-1 and clinico-pathological variables in DCIS. In IDC, Fra-1 expression correlated with aggressive phenotype markers, including: high grade, oestrogen receptor negativity and human epidermal growth factor receptor 2 (HER-2) positivity (P=0.001, 0.015 and 0.004, respectively), and marginally with the presence of metastasis (P=0.07). Fra-1 was more frequently positive in basal-like (34%) and in HER-2-positive (38.5%) subtypes than in luminal subtypes. Fra-1 presence did not correlate with survival. CONCLUSIONS: A high frequency of Fra-1 in DCIS tumours may be associated with early events in breast carcinogenesis. Although Fra-1 expression correlated with features of a more aggressive phenotype in IDC, no relationship with overall survival was found.

[Basal-like breast cancers: clinicopathological features and outcome]. / Carcinomas mamários de tipo basal: perfil clínico-patológico e evolutivo.

OBJECTIVE: The aim of our study was to investigate basal phenotype in a series of triple-negative (estrogen and progesterone receptors-negative and HER2-negative) invasive mammary carcinomas. METHODS: We selected 140 previously tested triple-negative tumors. Clinical, histopathological and survival data were obtained. A tissue microarray containing 2 cylinders from each tumor was constructed and immunohistochemistry for estrogen receptor (ER), progesterone receptor (PR), HER2, cytokeratins (CK) 5 and 14, EGFR, p63, and p53 was performed. We considered basal like-cancers (BLC) those tumors that were ER/PR/HER2-negative and CK5-positive. RESULTS: We found 105 cases of BLC from 140 triple-negative tumors (frequency=75.0%). The mean age at diagnosis was 54.8 years-old and 34.3% were premenopausal women. The majority of tumors were high grade (83.7%) and of ductal/no-special-type (80.8%). Triple-negative tumors showed immunoreactivity for CK5 (75.0%), CK14 (29.0%), EGFR (28.6%), p63 (28.6%), and p53 (67.1%). Tumor size larger than 5cm was observed in 41 cases (39.0%) and axillary metastases were detected in 61 patients (59.2%). Follow-up was recorded for 89 patients (mean=51 months): 45 patients (50.5%) with no evidence of disease; 6 patients (6.7%) were alive with disease; and 38 patients (42.6%) died of the disease. Relapse was detected in 42 women (47.1%), lungs, brain, and bones being the most common sites of metastasis. The mean overall survival was 36 months and the mean disease-free interval was 28 months. CONCLUSION: Our findings confirmed that BLC are poor prognosis and highly-frequent carcinomas among triple-negative tumors, similar to data previously reported in North American and European patients.

Carcinomas mamários de tipo basal: perfil clínico-patológico e evolutivo / Basal-like breast cancers: clinicopathological features and outcome

OBJETIVO: Investigar a frequência de carcinomas mamários de fenótipo basal em uma série de tumores triplo-negativos (TTN), definidos pela negatividade para receptores de estrógeno (RE), de progesterona (RP) e HER2. MÉTODOS: Selecionamos 140 TTN, obtendo-se características clínico-patológicas e sobrevida. Microarranjo de tecido (2 cilindros de cada tumor) foi construído e submetido à imunoistoquímica para RE, RP, HER2, citoqueratinas (Cks) 5 e 14, EGFR, p63 e p53. Consideramos carcinomas de fenótipo basal os tumores negativos para RE, RP e HER2, e positivos para CK5. RESULTADOS: Encontramos 105 carcinomas de fenótipo basal entre 140 TTN (frequência=75 por cento). A idade média das pacientes foi de 54,8 anos, sendo que 34,3 por cento estavam na pré-menopausa. A maioria dos tumores foi classificada como carcinoma ductal invasor de alto grau. Os TTN exibiram positividade para CK5 (75,0 por cento), CK14 (29 por cento), EGFR (36,4 por cento), p63 (28,6 por cento) e p53 (67,1 por cento). Estadiamento avançado da doença foi observado em 52 pacientes (50 por cento), com diâmetro tumoral maior que 5 cm em 41 casos (39 por cento) e metástases axilares em 61 casos (59,2 por cento). Seguimento clínico foi obtido em 89 pacientes (média=51 meses). Destas, 45 pacientes (50,5 por cento) evoluíram sem doença; 6 (6,7 por cento) estavam vivas com doença e 38 (42,6 por cento) morreram pelo câncer. Recidiva sistêmica ocorreu em 42 pacientes (47,1 por cento), sendo pulmões, cérebro e ossos os principais sítios de metástases. As médias das sobrevidas global e livre de doença foram de 36 e 28 meses, respectivamente. CONCLUSÕES: Nosso estudo confirma comportamento clínico agressivo e elevada frequência dos carcinomas de fenótipo basal entre os TTN, semelhante ao descrito em casuísticas norte-americanas e europeias.

OBJECTIVE: The aim of our study was to investigate basal phenotype in a series of triple-negative (estrogen and progesterone receptors-negative and HER2-negative) invasive mammary carcinomas. METHODS: We selected 140 previously tested triple-negative tumors. Clinical, histopathological and survival data were obtained. A tissue microarray containing 2 cylinders from each tumor was constructed and immunohistochemistry for estrogen receptor (ER), progesterone receptor (PR), HER2, cytokeratins (CK) 5 and 14, EGFR, p63, and p53 was performed. We considered basal like-cancers (BLC) those tumors that were ER/PR/HER2-negative and CK5-positive. RESULTS: We found 105 cases of BLC from 140 triple-negative tumors (frequency=75.0 percent). The mean age at diagnosis was 54.8 years-old and 34.3 percent were premenopausal women. The majority of tumors were high grade (83.7 percent) and of ductal/no-special-type (80.8 percent). Triple-negative tumors showed immunoreactivity for CK5 (75.0 percent), CK14 (29.0 percent), EGFR (28.6 percent), p63 (28.6 percent), and p53 (67.1 percent). Tumor size larger than 5cm was observed in 41 cases (39.0 percent) and axillary metastases were detected in 61 patients (59.2 percent). Follow-up was recorded for 89 patients (mean=51 months): 45 patients (50.5 percent) with no evidence of disease; 6 patients (6.7 percent) were alive with disease; and 38 patients (42.6 percent) died of the disease. Relapse was detected in 42 women (47.1 percent), lungs, brain, and bones being the most common sites of metastasis. The mean overall survival was 36 months and the mean disease-free interval was 28 months. CONCLUSION: Our findings confirmed that BLC are poor prognosis and highly-frequent carcinomas among triple-negative tumors, similar to data previously reported in North American and European patients.

Perfil de citoceratinas e sua relação com diferenciação, e fatores clínico-morfológicos em carcinomas ductais SOE de mama estudados em “array de tecido” (tissue microarray – TMA) / Cytokeratin profile: relation with differentiation, clinical and morphological features in invasive ductal carcinomas of the breast using tissue microarrays

Com o desenvolvimento de novas técnicas de avaliação dos perfis de expressão gênica (PEG) foram identificados subgrupos de risco diferenciado de carcinomas mamários. No entanto, as diferenças nos PEG não se traduzem em características morfológicas que possam ser prontamente identificadas no exame anatomopatológico rotineiro. ... A maioria dos estudos da literatura tem avaliado o perfil de expressão das CKs em grupos heterogêneos de tumores mamários diluindo, assim, o significado mais preciso dos resultados. Por este motivo, o objetivo principal do presente trabalho foi verificar numa amostra exclusiva de 1.167 casos de carcinomas ductais invasivos (CDI), com acompanhamento clínico médio de 62 meses, a associação da revisão padronizada das características clínico-morfológicas e dos perfis de expressão IIQ de 15 marcadores prognósticos e preditivos, otimizando as reações através da técnica de TMA. ... RESULTADOS: No total destes 1.167 casos de CDI, observamos significância estatística (P < 0,05) de diversas variáveis clínicas e morfológicas para a sobrevida global em 5 anos nas análises univariadas dos casos de ambos os grupos (índice mitótico, graus histológico, nuclear e extensão da necrose). No grupo de doença avançada, houve significância da presença de componente in situ associado ao invasivo, do status nodal e da intensidade do infiltrado inflamatório peritumoral. ... CONCLUSÃO: A revisão padronizada das variáveis clínico-morfológicas fornece importantes subsídios para a decisão da melhor conduta terapêutica nos casos de CDI. Verificamos que o subgrupo IIQ basalóide apresenta a pior evolução clínica nos grupos da amostra total e doença avançada, com relevância prognóstica (P < 0,05). A análise IIQ com as CKs basais complementa os critérios de decisão de conduta terapêutica e a associação de novos marcadores poderá adicionar informações relevantes aos fatores preditivos e prognósticos já estabelecidos na prática oncológica.

Through development of new techniques of gene expression profiling (GEp) diverse risk subgroups of breast carcinomas were identified. However, the differences within GEP do not convert into readily identiflable morphological characteristics in routine histological examination. ln cases with the same clinical stage and similar histological graduation it may be difficult to reach optimal therapeutic decisions. Even in case of early diagnosis, many cases have unfavorable clinical outcome. lmmunohistochemical stains (lHC) with biomarkers based on GEP findings showed that the most relevant groups are the hormone receptor (HR) expressing, the HER2 overexpressing and the basal-like carcinomas. This later group is typically HR - and HER2 - (ie not amplified) and shows expression of one or more basal cytokeratins (CKs) of the mammary ductal epithelium (CKs 5,6; 14 and 17). Most studies have been analyzing the CK profile in heterogeneous groups of mammary tumors, thus, diluting a more precise significance of the results. Before this background, the main objective of this study was to verify in a group of 1.167 cases of ductal invasive carcinomas (lDC) exclusively, with medium clinical follow up of 62 months, the association of standardized revision of the clinical and morphological characteristics and the IHC profile of 15 prognostic and predictive markers, optimizing the technical reactions applying the tissue microarray technique. The markers utilized were CK 5,6; 8; 13; 14; 17; 18; HR (estrogen and progesterone), HER2, EGFR; p53; p63; Ki-67; psoriasin and ezrin. The patients were divided in two groups, according to the clinical staging (CS): localized disease (CS I and ll) and advanced disease (CS lll and lV). RESULTS: The five year overall survival analyses of these 1.167 IDC cases showed statistical signiflcant results (P < 0,05) of some clinical and morphological variables for both groups of patients (mitotic index, histological and nuclear grades, necrosis extension). Within the advanced disease group significance of the rn srtu associated with the invasive component, the nodal status and the intensity of the inflammatory peritumoral infiltrate was observed. Regarding the IHC profiles, the HR expressing, the HER2 overexpressing and the basal-like were significant. Ezrin showed signiflcance on the univadable analysis for the advanced disease group (p = 0,023). coNCLUSIoN: The standardized revision of the clinical and morphological variables provides important information for the clinical decision making in IDC patients. We verified that the IHC basal-like subgroup shows the worst clinical outcome in the whole group (clinical stages I - lV) of cases and in the group of advanced disease (clinical stages lll and lV) of this study (P < 0,05). ln the group of localized disease, the subgroup HER2-positive had the worst prognosis. The IHC analysis with the basal cKs provides important aditional inputs for the clinical decision making. The association of new markers may add relevant information to the established predictive and prognostic factors of the clinical oncology practice (AU)