Breast hamartoma: reassessment of an under-recognised breast lesion.

AIMS: Breast hamartomas are an under-recognised lesion because they lack a distinctive microscopic appearance. Microscopic diagnosis can often conclude 'no significant lesion' or 'normal breast tissue', leading to repeated biopsies and diagnostic delay. We describe the histological, immunohistochemical and radiological features of breast hamartomas with the aim of identifying specific signs to facilitate their diagnosis and to differentiate them from normal breast and fibroepithelial lesions. METHODS AND RESULTS: Forty-seven breast hamartomas were reassessed (histological diagnosis and imaging features). An immunohistochemical study [oestrogen receptor (ER), progesterone receptor (PR), CD34, high-mobility group A2 (HMGA2)] was performed. On breast imaging, hamartomas most often presented as probably benign solid masses with circumscribed margins and variable densities. Histologically, breast hamartomas resembled normal breast, although their stromal component was predominant, separating randomly scattered epithelial elements with areas of pure collagenous stroma. Pseudoangiomatous stromal hyperplasia (PASH) was present in 93.6% of cases and CD34 antibody highlighted intralobular, perilobular and interlobular distribution of CD34-positive fibroblasts. By comparison, CD34 was mainly expressed in the intralobular normal breast tissue stroma. Hamartoma stromal cells expressed HMGA2, ER and PR in 79%, 66% and 76.3% of our cases, respectively, compared to 7.7%, 23% and 19% in normal breast tissue, respectively (P < 0.0001; P = 0.0005; P < 0.0001). CONCLUSIONS: After ascertaining that core needle biopsy is effectively intralesional, breast hamartomas can be diagnosed with confidence by taking into account the presence of stromal changes, PASH, interlobular distribution of CD34-positive fibroblasts, HMGA2 and hormonal receptor stromal expression.

Residual cancer burden index and tumor-infiltrating lymphocyte subtypes in triple-negative breast cancer after neoadjuvant chemotherapy.

PURPOSE: There is a need to refine the prognosis of triple-negative breast cancer (TNBC) patients after neoadjuvant chemotherapy (NAC) and to study the influence of the tumor microenvironment. We evaluated the prognostic value of pathological and immune markers in TNBC with residual disease (RD) after NAC. METHODS: In a series of 186 TNBC patients treated by NAC, we assessed the prognostic value of the Residual Cancer Burden (RCB) index. In 109 patients with RD, we studied the impact of clinicopathological features and tumor immune response in the residual tumor on overall survival (OS) and distant recurrence-free interval (DRFI). RESULTS: In the whole group, the OS and DRFI, at 3 years, were statistically different between the different classes of RCB (P = 0.0004 and P < 0.0001, respectively). In univariate analysis of the RD group, low RCB index and high ratios of stromal tumor-infiltrating lymphocytes (TILs), CD3 + TILs, CD4 + TILs, CD8 + TILs, and IDO1-positive cells were significant favorable prognostic factors for DRFI at 3 years. In the final multivariate model, CD4 + TILs and RCB index showed a statistically independent prognostic significance for DRFI [Hazard Ratio (HR) 2.88 (95%CI 1.34-6.17), P = 0.007 and HR 12.04 (95%CI 2.78-52.23, P < 0.0001), respectively]. The CD4 + TIL levels influenced survival in the different RCB classes with a significant effect observed in RCB-II and RCB-III classes (P = 0.05 and P = 0.05, respectively). CONCLUSIONS: These results suggest that the combination of pathological (RCB index) and tumor micro-environmental features (CD4 + TILs) help refining the prognosis of TNBC patients with RD following NAC.

GREB1-CTNNB1 fusion transcript detected by RNA-sequencing in a uterine tumor resembling ovarian sex cord tumor (UTROSCT): A novel CTNNB1 rearrangement.

Mutations of CTNNB1 have been implicated in tumorigenesis in many organs. However, tumors harboring a CTNNB1 translocation are extremely rare and this translocation has never been reported in a uterine mesenchymal neoplasm. We report a novel translocation t(2;3)(p25;p22) involving the GREB1 (intron 8) and CTNNB1 (exon 3) in a uterine tumor resembling ovarian sex cord tumor (UTROSCT), which exhibited extrauterine metastasis. The translocation detected by RNA-sequencing was validated by RT-PCR, and resulted in nuclear expression of ß-catenin. Juxtapositioning with GREB1, which is overexpressed in response to estrogens, resulted in overexpression of a truncated and hypophosphorylated nuclear ß-catenin in the primary and recurrent tumors. This accumulation of nuclear ß-catenin results in a constitutive activation of the Wnt/ß-catenin signaling pathway with a major oncogenic effect. The CTNNB1 gene fusion, promoted by an estrogen-responsive gene (GREB1), could be a potential driver of tumorigenesis in this case and a therapeutic target with adapted inhibitors. RT-PCR and immunohistochemistry performed on 11 additional UTROSCTs showed no CTNNB1 fusion transcript or nuclear ß-catenin immunoreactivity.

Primary cutaneous follicle center lymphoma with Hodgkin and Reed-Sternberg-like cells: a new histopathologic variant.

Primary cutaneous follicle center lymphoma (PCFCL) is the most frequent cutaneous B-cell lymphoma. A 62-year-old man presented with a solitary indolent subcutaneous nodule for 3 years duration, without other abnormalities. Histological examination showed lymphoproliferation with a nodular growth pattern characterized by fibrous collagen bands surrounding nodules. The nodules were composed of medium-sized centrocytes admixed with many large multilobulated and lacunar cells without eosinophils or granulomatous aspect. Hodgkin-like cells were CD30+, CD15+, PAX5+, OCT2+, BOB1+, MUM1+, Ki67+, Bcl6+ and focally CD20+ and EMA-, CD79a-, Bcl2- and CD10-. The medium-sized cells were CD20+, CD79a+, Bcl2+, Bcl6+ and CD10+, enmeshed in a network of CD21-positive follicular dendritic cells. Epstein-Barr virus detection was negative. Interphase fluorescence in situ hybridization showed the absence of BCL2 or BCL6 rearrangement. In such a case, the presence of Hodgkin-like cells intermixed with the tumor population may result in a pitfall diagnosis of classical Hodgkin lymphoma (CHL). Differential diagnoses to be ruled out are secondary or primary skin localization of rather CHL, or systemic follicular lymphoma. Several clinical, radiological, histological, immunohistochemical and molecular arguments indicated the diagnosis of PCFCL. To our knowledge, this is the first report of PCFCL with Hodgkin-like cells.

From palliative to curative intent: PET/CT findings in the light of breast cancer intrinsic subgroup.

PURPOSE: Among breast cancer subgroups, Luminal A is the subgroup with the best prognosis. We report the case of a young woman presenting with a localized luminal A breast cancer with a suspicious liver lesion on initial positron emission tomography (PET)/computed tomography (CT) scan staging. CASE DESCRIPTION: A 31-year-old woman presented with localized breast cancer accessible to curative treatment. However, PET/CT staging revealed an increase of focal activity in the liver, suspicious of a secondary malignant localization, changing the care towards palliative intent. Discrepancy between breast cancer luminal A subtype and the liver lesion led to further investigations (contrast ultrasound, magnetic resonance imaging, and biopsy), excluding a malignant process, and were in favor of toxic hepatitis, probably secondary to herbal tea consumption. CONCLUSIONS: Questioning PET/CT findings in light of the cancer subtype enabled us to rectify the diagnosis and allow this patient to be treated with curative intent.

A single-center study on total mastectomy versus skin-sparing mastectomy in case of pure ductal carcinoma in situ of the breast.

INTRODUCTION: Ductal carcinoma in situ (DCIS) accounts for 15% of all breast cancers and generally, the prognosis is good if treated optimally. The standard treatment includes breast conservative surgery along with adjuvant radiotherapy. Skin-sparing mastectomy (SSM) preserves the breast skin envelope but its oncological safety poses a few concerns. Moreover, no DCIS-specific studies have compared the local recurrence (LR) rate following total mastectomy (TM) or SSM. We evaluated the LR rate in DCIS patients who underwent either TM or SSM. METHODS: This is a retrospective study on women who underwent mastectomy with or without immediate breast reconstruction or secondary reconstruction for pure DCIS of the breast. All patients treated at Institut Bergonié by mastectomy for DCIS from January 1990 to December 2010 were included. LR and overall survival (OS) rates were estimated. RESULTS: The study population included 399 patients who were categorized into two groups, 207 in the TM group and 192 in the SSM group. At 10 years of follow-up, the LR rate was 0.97% in the TM group and 1.04% in the SSM group (p = NS). The OS of the entire population was 94.7% [95% CI; 91.6-96.7], 92.8% [95% CI, 87.9-95.8] for the TM group and 96.8% [95% CI, 91.6-98.8] for the SSM group. CONCLUSIONS: In our study, the LR rate following mastectomy is low, regardless of the surgical technique used, with an excellent OS at 10 years.

Pulmonary carcinosarcoma with heterologous component: report of two cases with literature review.

Carcinosarcoma is an uncommon malignant biphasic tumor that accounts for less than 1% of all lung cancers. It is defined by coexisting histologic elements of carcinomatous and sarcomatous components. We report two cases of carcinosarcoma in a 68-year-old patient and a 78-year-old patient explored for lung masses. Macroscopically, the resected tumors were 7 and 10 cm in diameter. Histologically, they consisted in adenosquamous carcinoma with osteosarcoma in one case and adenocarcinoma with chondrosarcoma in the other case.

A rare and particular form of goiter to recognize.

Dyshormonogenetic goiter is a rare cause of congenital hypothyroidism occurring due to a lack of enzymes necessary for the synthesis of thyroid hormones. It is morphologically characterized by architectural and cellular pleomorphism that may mimic thyroid malignancy and cause difficulties in differential diagnosis. We report a new case occurring in a 37-year-old male with history of hypothyroidism since the age of 6 years treated by L-thyroxin. He developed a progressively slow growing multinodular goiter and consulted for recent dyspnea. Computed tomography scan showed a multinodular plunging goiter with compression of the trachea and vessels in the left side. A total thyroidectomy was performed. Gross examination revealed an enlarged and multinodular thyroid gland, presenting hemorrhagic changes in the larger nodules. Histologically, the features were consistent with dyshormonogenetic goiter. The literature on the histopathology of dyshormonogenetic goiter is reviewed and clues to avoid inappropriate overdiagnosis of malignancy are given.