Inflammatory breast carcinoma and locally advanced breast carcinoma: characterisation with MR imaging.

PURPOSE: This study was done to identify the typical magnetic resonance (MR) imaging findings of inflammatory breast carcinoma (IBC) in comparison with noninflammatory locally advanced breast carcinoma (LABC). MATERIALS AND METHODS: MR images of 30 patients with IBC (T4d) were compared with those of a cohort of 30 patients with LABC (T3/T4a-c). The age distribution was approximately equal in the two groups. MR images were assessed for the following features: skin thickening (>4 mm), skin oedema, architectural distortion, enhancement pattern (mass-like/non-mass-like), time-signal intensity curve (continuous-persistent type/wash-out type), skin enhancement. Fisher's exact text was used to compare MR imaging appearances of IBC and LABC (significant p value <0.05). RESULTS: Skin involvement and enhancement pattern differed between groups: skin thickening was present in 16/30 IBC (53%) vs 8/30 LABC cases (27%, p=0.06), skin oedema was present in 26/30 IBC (87%) vs 8/30 LABC (27%, p < 0.0001), and skin enhancement in 10/30 IBC (33%) vs 2/30 LABC (7%, p=0.02); non-mass-like enhancement was present in 22/30 IBC (73%) vs 12/30 LABC (40%, p=0.02). CONCLUSIONS: IBC is a distinct clinical and pathological entity resulting in typical MR imaging features. Skin changes (thickening, oedema, enhancement) related to neoplastic involvement of the dermal lymphatics are suggestive of IBC and should prompt a skin biopsy to confirm or rule out the diagnosis.

Wnt (canonical and non canonical) pathways in breast carcinoma with extensive vascular invasion and inflammatory breast carcinoma.

BACKGROUND: Breast carcinoma with extensive peritumoral vascular invasion (ePVI-BC) is a cancer with massive vascular invasion (>10) detected in more than one slide. This neoplasm shows clinic-pathological affinity with inflammatory breast carcinoma (IBC). In this paper we evaluate their biological relationship through the study of surrogate markers (ß-catenin and NFAT5) of Canonical (cWnt) and non-canonical (nWnt) Wnt pathways activation. METHODS: By immunoistochemistry, we investigate ß-catenin and NFAT5 in 39 IBC, 74 ePVI-BC and 84 control cases (CG-BC). RESULTS: cWnt was activated in 100 % of ePVI-BC, in 64 % of IBC and 10 % of CG-BC. nWnt was activated in 20 % of ePVI-BC, 50 % of IBC and 1% of CG-BC. The prognosis of carcinomas with nWnt activated was poor similar to IBC. The statistical analysis evidences as both the pathways are synergistic in malignant progression and survival time. ß-catenin show an important association with prognostic factors and NFAT5 shows a relevant prognostic role on OS (p = 1.5*10-6) and DFS (P = 1,2*10-4). nWnt is associated with a worse prognosis independently of cWnt. cWnt is associated with adverse prognosis (DFS p = 0.0469; OS p = 0.004891) but its prognostic role is indifferent in carcinoma with nWnt activated. CONCLUSIONS: Canonical Wnt pathway is involved in malignant progression with dominant role for vascular invasion whereas non canonical Wnt pathway plays an important role on survival time including the capacity to identify carcinomas with IBC-like prognosis. Furthermore ePVI may represent a "prodromal form of IBC" as demonstrated by its clinicopathological and biological similarity with IBC.

B3 breast lesions determined by vacuum-assisted biopsy: how to reduce the frequency of benign excision biopsies.

PURPOSE: The aim of this study was to identify parameters allowing differentiation among the diverse group of B3 lesion at stereotactic vacuum-assisted biopsy (VAB) to identify patients with a low risk of cancer and who can therefore be referred for follow-up rather than surgery and thus reduce the number of unnecessary surgical procedures. MATERIALS AND METHODS: Among 608 VAB procedures performed for nonpalpable ultrasound (US)-occult mammographic abnormality, 102 cases of B3 were included in this study. Mammographic lesion type, lesion size, Breast Imaging Reporting and Data System (BIRADS) category, number of specimens per lesion and presence of atypia were retrospectively analysed. Results were compared with histological findings at surgery (53 cases) or mammographic findings during follow-up (49 cases). Statistical analysis was performed with univariate analysis (chi-square test), and statistical significance was set at p<0.05. RESULTS: The majority of cases were depicted as isolated microcalcifications (82.3%), were smaller than 10 mm (80.4%), had a low level of radiological suspicion (64.7%) and had 11 or more cores sampled (94.1%). Atypia at VAB was reported in 60 of 102 cases (58.8%). Carcinoma was found at excision in 5/60 (8%) B3 lesions with atypia and in no B3 lesions without atypia (p=0.146). Cancer at surgery was more frequent among cases of isolated microcalcifications (p=0.645), cases with high radiological suspicion (p=0.040) and those with a smaller number of cores sampled (borderline significant p=0.064). CONCLUSIONS: On the basis of our experience, the presence or absence of atypia in our series proved to be the reliable criterion to prompt or avoid surgery in cases with a VAB finding of B3 lesion. This criterion may therefore be adopted in practice to more accurately select patients for surgery.

Fischer's score criteria correlating with histopathological prognostic factors in invasive breast cancer.

PURPOSE: This study aimed to evaluate whether the Fischer score criteria on contrast-enhanced magnetic resonance (CE-MR) imaging could correlate with histopathological prognostic factors in invasive breast cancer. MATERIALS AND METHODS: Seventy-two women with histologically proven invasive breast cancer underwent preoperative CE-MR imaging. Images were assessed for the following parameters, according to the scoring system described by Fischer in 1999: tumour shape, margins, internal enhancement, signal intensity increase, signal intensity course and overall Fischer score. Evaluated histopathological prognostic factors included histological type, associated extensive intraductal component, diameter, lymph node metastasis, tumour grade, and oestrogen receptor (ER), progesterone receptor (PgR), Ki67 proliferation, oncogene c-erbB-2 (HER2/neu) expression. Fisher's exact test was used to correlate the CE-MR imaging parameters and histopathological findings (with significance set a p < 0.05). RESULTS: Fischer's score was 0-4 in 14/72 (19%) cases, >4 in 58/72 (81%) and 3 in 5/72 (7%; false negative), with a sensitivity of 93%. A significant correlation (p=0.02) was found between stellate-dendritic shape and the presence of an associated extensive intraductal component (EIC), which was found in 78% of stellate tumours vs. 49% of round-oval tumours. A significant correlation (p=0.039) was found between Ki67 expression and signal intensity course (Ki67 overexpression was present in 81% of tumours with washout course vs. 21% with plateau course). CONCLUSIONS: The CE-MR imaging findings that correlate with prognostic factors are shape and signal intensity curve. Fischer's multifactorial analysis was helpful in the interpretation of CE-MR images, showing a sensitivity of 93% for invasive breast cancer.

CROCC-mutated rhabdoid colorectal carcinoma showing in intercellular spaces lamellipodia and cellular projections revealed by electron microscopy.

BACKGROUND: Rhabdoid colorectal carcinoma (RC) is a rare lesion localized to the proximal colon of patients with a mean age at diagnosis of around 70 years. This tumor shows an aggressive behavior with an overall survival period shorter than 12 months. The diagnostic hallmark is the presence of rhabdoid cells. Alterations in chromatin remodeling (SMARCB1) and in the centrosome structure (CROCC) are reported in RC usually BRAFmut and MSI-H. RKO intestinal neoplastic cells culture (BRAFmut, SMARCB1wt, MSI-H) with CROCC knockdown exhibit rhabdoid features and develop prominent projections from the edge of the cell. METHODS: Here, we investigated two cases of CROCCmutSMARCB1wt RC by scanning and transmission electron microscopy (SEM, TEM). RESULTS: TEM confirmed the diagnostic presence of intermediate cytoplasmic filaments and nucleolar margination. SEM showed cellular protrusions (lamellipodia) in the intercellular spaces not evident at light microscopy. CONCLUSIONS: These protrusions CROCC-related might represent the pathogenetic mechanism underlying the rhabdoid aggressive behavior, independently of tumor staging. To our knowledge, the SEM technique was applied in the study of this neoplasm for the first time.

The importance of immunohistochemistry in the differential diagnosis of molar disease.

The differential diagnosis among complete moles, partial moles and hydatidiform abortions may be challenging during routine diagnostic activity. These entities share the histological aspect of enlarged villi, but here we summarize also some peculiar features of all of them. If histology does not clarify this distinction, the immunohistochemistry is the most important tool for pathologists to complete such diagnosis. The correct management of immunohistochemistry and of further possible analysis is also reviewed. Lastly, the most important antibodies, starting from p57, are presented.

Pathological complete response in a patient affected by multiple synchronous, breast and lung primary malignancies: a case report and review of the literature.

A pathological complete response in a patient affected by multiple synchronous, breast and lung primary malignancies is reported. A 63-year-old woman presented with an invasive ductal carcinoma of the breast and a lung adenocarcinoma. After multidisciplinary discussion, the patient underwent pulmonary left lower lobectomy followed by radio-chemotherapy with cisplatin and vinorelbine and started hormone therapy with letrozole. Ten months later, a left mastectomy with axillary lymph nodes dissection was performed. Histologically, a pathological complete response (pCR) was documented. With a review of the Literature, we discuss the issue of multiple primary malignancies, with its diagnostic and therapeutic implications. In cases of multiple synchronous malignancies it has been highlighted the importance of the choice of the best therapeutic approach for both the malignancies, reducing collateral individual effects.

bcl-2 but not p53 expression is associated with resistance to chemotherapy in advanced breast cancer.

Programmed cell death is an important determinant of the response to chemotherapy. Among the factors controlling this process, a significant role is played by bcl-2 and p53, the expression of which, together with estrogen receptor content and tumor proliferative activity, was investigated by means of immunohistochemistry in 55 advanced breast cancer patients (median age, 60 years; range, 25-71 years). Analysis of bcl-2 expression identified two groups of patients with a significant difference in response rate. A total of 17 patients (31%) responded to chemotherapy (5 had a complete response and 12 had a partial response): 14 of 32 (44%) bcl-2-negative patients (< 40% stained cells) and only 3 of 23 (13%) bcl-2-positive patients (> or = 40% of stained cells; P = 0.019 by Fisher's exact test). The two groups were well balanced in terms of age, performance status, disease-free survival, menopausal status, and type of chemotherapy. bcl-2-negative tumors showed a tendency toward a higher p53 expression and proliferation rate, whereas an excess of bone as the dominant disease site was evident among the bcl-2-positive ones. However, the only variable to result significantly different between the two groups was estrogen receptor expression (P = 0.004). A multivariate logistic regression model showed that bcl-2 maintained its power of discriminating two groups with a different probability of responding to chemotherapy, although the greatest contribution was given by dominant disease site and type of chemotherapy. In conclusion, the results of this study suggest a possible role for bcl-2 in predicting resistance to chemotherapy.

Apparent renal cell carcinomas in tuberous sclerosis are heterogeneous: the identification of malignant epithelioid angiomyolipoma.

Renal epithelial tumors (carcinoma and oncocytoma) have been reported with higher a frequency than expected in patients with the tuberous sclerosis complex. However, the recent identification of a monotypic, epithelioid variant of angiomyolipoma, closely simulating renal cell carcinoma, has cast doubt on the real frequency of carcinoma. Immunohistochemical analysis with a panel of antibodies, including melanogenesis marker HMB45, can discriminate between carcinoma and carcinoma-like angiomyolipoma. We studied five tumors previously reported as carcinoma and found that only one of them showed an immunohistochemical phenotype indicative of an epithelial tumor (Ker+, HMB45-). Three tumors exhibited a phenotype compatible with the monotypic epithelioid variant of angiomyolipoma (HMB45+, Ker-), and two of the three patients died of metastatic disease. The last patient had unusual clinical features, and the tumor was positive both for HMB45 and keratin. It is concluded that (1) renal cell carcinoma is less common in tuberous sclerosis complex than previously believed, (2) some cases called renal cell carcinoma probably represent a monotypic, epithelioid variant of angiomyolipoma, and (3) epithelioid angiomyolipoma is a potentially malignant tumor with invasion and metastases. These findings indicate that all reported renal carcinomas in tuberous sclerosis complex, therefore, must be reevaluated.

Renal angiomyolipoma with epithelioid sarcomatous transformation and metastases: demonstration of the same genetic defects in the primary and metastatic lesions.

Angiomyolipoma (AML) is a benign neoplasm that occurs either sporadically or in patients with tuberous sclerosis complex (TSC) and shows frequent allelic losses at chromosome arm 16p. It has been suggested recently that the melanogenesis marker-positive perivascular epithelioid cell (PEC) has been found consistently in AML. The authors report a 50-year-old woman without evidence of TSC affected by classic renal AML containing an area composed of atypical epithelioid cells with the same morphoimmunophenotypic characters of PEC. After 7 years from surgical removal of the lesion, the patient developed a local recurrence and successive lung and abdominal metastases that showed morphologic and immunohistochemical features overlapping those of the epithelioid area of the previously removed AML. Genetic analysis showed that the classic AML and its epithelioid area as well as the pulmonary and abdominal metastases shared the same allelic loss on chromosome arm 16p. Based on these findings, the authors view this case as evidence of a malignant transformation of a classic AML with morphologic, immunophenotypic, and genetic demonstration of its clonal origin.

Breast carcinoma with positive results for melanoma marker (HMB-45). HMB-45 immunoreactivity in normal and neoplastic breast.

HMB-45 (melanocytic cell-specific monoclonal antibody) immunoreactivity has been detected by the immunoperoxidase technique in the cytoplasm of 2 of 100 breast carcinomas. In addition, normal breast lobules and ducts were occasionally found to have positive results in 6 of 100 cases. These findings indicate the need to exercise caution in the interpretation of HMB-45 immunoreactivity for immunohistochemical characterization of neoplasms.

A method for detection of human papillomavirus DNA in stored slides of stained cervical smears.

A simple method was developed for extraction of DNA from stored slides of Papanicolaou stained cervical smears. HPV type 16 DNA was detected by DNA hybridization in 7/10 samples from known HPV-16 positive patients, whereas the 10 samples from negative patients were also negative with our assay. Using our method for obtaining data from stained cervical smears, it will be possible to design and perform historical cohort studies on stored material.

Immunocytochemical detection of cell proliferation-related antigens in cytologic smears of human malignant neoplasms using PC10, reactive with proliferating cell nuclear antigen, and Ki-67. A comparative study.

Cytospins of the MCF-7 cell line and 93 consecutive smears of human malignant neoplasms were immunochemically evaluated for the expression of proliferating cell nuclear antigen (PCNA) and Ki-67-related antigen. Results expressed as the labeling index (LI) were compared with histologic sections. The PCNA LI and Ki-67 LI were lower in cytologic smears than in histologic sections, though the differences were not statistically significant. A positive linear relationship was found between these markers in both cytologic and histologic samples. The PCNA LI was generally lower than the Ki-67 LI, but in seven malignant neoplasms, PCNA LI was greater than the corresponding values of the KI-67 LI. We conclude that cell proliferation can be reliably evaluated on cytologic preparations; PCNA may behave as a Ki-67-like reagent in some tumors, and PCNA may sometimes overestimate the cell growth fraction assessed by Ki-67 immunoreactivity.

Methodological aspects of the immunostaining of proliferating cell nuclear antigen (PCNA) in cytospin preparations of MCF-7 cell line.

Cytospins of a human breast cancer cell line (MCF-7) were studied for the expression of PCNA, a cell cycle-related protein, using a variety of fixation and immunostaining procedures. The best fixative for PCNA was found to be buffered formaldehyde solution at 4 degrees C followed by methanol at 20 degrees C, whereas alcoholic fixatives decreased greatly the PCNA immunoreactivity. Air-drying procedures of cytospins prior to and after fixation greatly undermined the PCNA immunostaining. A modified immunoperoxidase method provided a stronger staining of the PCNA-reactive cells than the alkaline phosphatase anti-alkaline phosphatase (APAAP) technique. PCNA immunoreactivity could be maintained up to 2 mo, putting slides in methanol at -20 degrees C. In conclusion, our report indicates that PCNA is a labile antigen, which may critically be affected by temperature and air-drying procedures.

Expression of proliferating cell nuclear antigen, Ki-67 antigen, estrogen receptor protein, and tumor suppressor p53 gene in cytologic samples of breast cancer: an immunochemical study with clinical, pathobiological, and histologic correlations.

Sixty-six unselected breast cancers were analyzed in cytologic smears and histologic sections for the expression of Ki-67, proliferating cell nuclear antigen (PCNA), estrogen receptor protein (ERP), and p53 protein using a standard immunochemical method. The results, expressed as both positive cases and labelling index (LI), were compared with clinical and pathobiological variables. Ki-67 and PCNA immunostaining was seen in all cases, whereas ERP was detectable in 46/63 cases and p53 protein in 20/66 cases. The expression of these markers was generally lower in cytology than in histology, though the differences were not statistically significant. PCNA-LI and Ki-67-LI were closely correlated (P < 0.001), the mean PCNA:Ki-67 ratio being 0.92 +/- 0.57. Occasional discrepancies, however, were found. PCNA and Ki-67 expression was associated with an increase in histologic grade and a decrease in ERP content of tumors, whereas p53 was statistically associated with no clinical or pathobiological variables. The data suggest that proliferative activity and oncogene overexpression may be reliably evaluated in breast cancer by FNA cytology, though PCNA is not a suitable indicator for cell proliferation. The results do not resolve the issue as to whether immunostaining for p53 protein constitutes a dedifferentiation product of the tumor, or is a fundamental aspect of the malignant progression. Survival studies in a larger series of tumors are thus needed to elucidate this point.

[Our experience in treating vulvar lichen sclerosus]. / La nostra esperienza nel trattamento del lichen sclerosus vulvare.

METHODS: The authors looking for a better treatment of vulvar lichen sclerosus, treated 10 patients by topical application of clobetasol propionate (twice a day for 45 days and once a day for additional 45 days). Before and after therapy changes of subjective symptoms were studied with Vaona algometer as well as the histological modifications found in the biopsies of lesions like atrophy, hyperkeratosis, inflammatory infiltration, sclerosis, hyalinization and edema. RESULTS: The results seem to confirm the good improvement of subjective symptoms for the itching and also for burning. The histological results were encouraging, in fact we noticed a marked reduction of inflammatory infiltration and an improvement of atrophy, hyperkeratosis, hyalinization and edema. CONCLUSIONS: The clinical and histological results seem to confirm the therapeutic effect of the use of clobetasol propionate for the treatment of vulvar lichen sclerosus.

[A case of brown tumor of the vomer]. / Osservazione di un caso di tumore bruno del vomere.

A case of brown-tumor of the vomer in a 21-year-old woman is described. The term giant cell lesions encompasses a variety of conditions. Three distinct entities are found in the facial area i.e. giant cell reparative granuloma, true giant cell tumor and brown-tumor. After having described the clinical, radiological and histopathological characteristics of the lesion, emphasis is placed on the importance of clinical, anamnestic, laboratory, radiological and histological findings in accurately differentiating the various types of giant cell lesions of the facial skeleton.