Cutaneous metastasis of rectal adenocarcinoma: a case report and literature review.

According to the latest data provided by Globocan 2020, the incidence of colorectal cancer ranks third, after lung cancer and breast cancer, becoming a more and more important global health issue. Of the cases diagnosed with colorectal cancer, more than 25% are diagnosed in the metastatic stage, with the presence of secondary tumors more frequently in the liver, lung and bone. Skin metastases from colorectal cancer are still rare today (< 4%). We want to present a rare, unique case in our department of a 74-year-old patient diagnosed 9 years ago with a malignant rectal tumor who, after a disease-free period of approximately 8 years and a half, developed multiple skin metastases of rectal adenocarcinoma.

Sirenomelia with associated systemic anomalies - an autopsy report in a full term neonate.

The mermaid syndrome, also known as sirenomelia, is considered an extremely rare congenital developmental disorder characterized by anomalies of the lower spine and lower limbs. Affected babies are born with partial or total leg fusion. Sirenomelia is thought to affect one in every 60,000 to 100,000 infants. We report a case of sirenomelia occurring in a 28-year-old multiparous woman, a heavy smoker with gestational diabetes. In the other 5 pregnancies, however, she gave birth to normal babies. The post mortem examination completed the diagnosis, revealing also multiple malformations of several systems: respiratory, gastro-intestinal, genito-urinary and cardiovascular. In our full term neonate case with grade VI sirenomelia, the presence of a single umbilical artery plus the abdominal aorta with an aberrant trajectory that ends in the umbilical cord differentiates this condition from caudal regression syndrome and also explains the under-development of pelvic organs (secondary to vascular steal phenomena).

FIGO 2018 stage IB endocervical adenocarcinomas: an international study of outcomes informed by prognostic biomarkers.

OBJECTIVE: Prognostic factors for endocervical adernocarcinomas are well known, but little is known about prognostic biomarkers influencing outcome for the newly defined International Federation of Gynecology and Obstetrics (FIGO) 2018 IB sub-stages. The aim of this study was to identify prognostic biomarkers influencing recurrence-free and overall survival for FIGO 2018 stage IB cervical adenocarcinoma sub-types. We sought to identify these factors using a large international multi-institutional series of cases. METHODS: Stage IB endocervical adenocarcinomas were retrospectively collected from nine international institutions; full slide sets (n=464) were used to assign prognostic biomarkers. Inclusion criteria were the following: FIGO stage IB endocervical adenocarcinomas with follow-up in which all paraffin blocks/glass slides were available for review and/or additional studies and the patient was surgically treated from 1985 to 2019. The types of specimens included in the study were conizations, trachelectomies, and simple/radical hysterectomies with or without lymph node samples. We excluded in situ carcinomas, squamous cell carcinomas, adenosquamous carcinomas, tumors with a neuroendocrine component, carcinosarcomas, and any tumor showing clinical, macroscopic, or microscopic features suggesting a lower uterine segment, uterine corpus, or an adnexal primary origin. Tumors treated with neoadjuvant chemotherapy and/or radiation therapy were also excluded, as well as biopsies and loop electrosurgical excision procedures. RESULTS: Of 464 cases, 225 (48%) were stage IB1, 177 (38%) were stage IB2, and 62 (13%) were stage IB3. Five-year and 10-year recurrence-free survivals were statistically different among stage IB sub-types (p=0.005). Silva pattern of invasion was significant for recurrence-free survival at 5 and 10 years (p=0.04); overall survival and recurrence-free survival were higher in human papillomavirus (HPV)-associated cases (p=0.007 and p=0.001, respectively) and in cases without lymphovascular invasion (p=0.004 and p=0.00001, respectively). Factors that significantly influenced recurrence-free survival were HPV-independent status (p=0.05; HR 2.31; 95% CI 1.02 to 5.46), presence of lymphovascular invasion (p=0.011; HR 3.50; 95% CI 1.33 to 9.19), and presence of lymph node metastasis (p=0.016; HR 2.66; 95% CI 1.20 to 5.90). CONCLUSION: HPV status and the presence of lymphovascular invasion are prognosticators in stage IB endocervical adenocarcinoma sub-types. These parameters should be included in future sub-staging modifications of FIGO stage IB endocervical adenocarcinomas and in treatment strategies.

Clinicopathologic Association and Prognostic Value of MELF Pattern in Invasive Endocervical Adenocarcinoma (ECA) as Classified by IECC.

Microcystic, elongated, and fragmented (MELF) pattern of myometrial invasion is correlated with lymphovascular invasion (LVI) and lymph node metastases in uterine endometrioid carcinoma but has not been described in endocervical adenocarcinoma (ECA). A total of 457 ECAs were collected, and clinical/morphologic parameters correlated with follow-up data. Potential associations between MELF pattern and age, human papillomavirus status, tumor size/grade, LVI, lymph node metastases, Silva pattern were analyzed. Statistical analyses of overall survival (OS), disease-free survival, progression-free survival (PFS) were conducted using Kaplan-Meier analysis, and compared using the Log-rank test. Of 292 ECAs analyzed, 94 (32.19%) showed MELF invasion pattern (MELF-positive). Significant statistical correlation was found between MELF-positive and tumor size (P=0.0017), LVI (P=0.007), Silva pattern (P=0.0005); age, human papillomavirus status, tumor grade, lymph node metastases did not correlate. Fifty-five of 292 patients recurred (18.83%): 18/94 (19.14%) MELF-positive, 37/198 (18.68%) MELF-negative. PFS in MELF-positive: 77.2% and 64.5% at 5 and 10 yr, respectively; PFS in MELF-negative: 82% and 68.5% at 5 and 10 yr, respectively. On multivariate analysis for PFS and other prognostic parameters, only LVI was statistically significant (P=0.001). OS in MELF-positive was 86% and 74.1% at 5 and 10 yr, respectively; OS in MELF-negative, was 89.7% and 86% at 5 and 10 yr, respectively. Median survival was worse in MELF-positive (199.8 mo) versus MELF-negative (226.1 mo); this was not statistically significant. On multivariate analysis for OS and other prognostic parameters, only tumor stage was statistically significant (P=0.002). In ECAs, MELF is not independently associated with survival. Pathologic characteristics of MELF-positive (size, LVI, Silva pattern) versus MELF-negative tumors differ significantly.

Differences in GATA3 expression among histological/molecular subtypes and grades in infiltrating breast carcinoma (IBC) are important in the diagnosis of metastatic breast carcinoma.

GATA-binding protein 3 (GATA3) is a sensitive and relatively specific marker in invasive breast carcinomas (IBC). The aim of the present study was to determine GATA3 expression among different histological and surrogate molecular breast carcinoma subtypes. Immunohistochemical staining of ER, PR, Ki67, HER2 and GATA3 was performed in a cohort of 84 consecutive cases of primary IBCs. The association of GATA3 expression with different histological subtypes, grades and surrogate intrinsic molecular subtypes was assessed. The overall positivity of GATA3 across various histological subtypes was 71.43% with no correlation with histological type (p = 0.849). Our study also confirmed that GATA3 exhibits a relatively high sensitivity for IBC (78.57%). GATA3 expression was positively correlated with low histological grades (G1/G2) vs. G3: p = 0.001) with most of G3 (57.89%) cases being negative and with luminal A (72.22%) and B (84.62%) subtypes (p = 0.00001) while most of the triple negative (87.5%) and HER2-overexpressed (66.67%) being negative. Caution must be payed however when dealing with an IBC metastasis of HER2-overexpressed or triple negative molecular subtypes or G3, since in these categories according to the present study, GATA3 is more frequently negative that previously reported and may be useless for diagnosis of tumor origin.

Analysis of Clinical-Pathological Data with Impact on Overall Survival in Male Breast Carcinoma: An International Multi-Institutional Study of 217 Cases.

Background: The aim of this study was to evaluate clinical-pathological parameters with impact on overall survival (OS) in male breast carcinoma (MBC). Methodology: We assessed OS at 5 years and at 10 years respectively, as well as OS according to age, tumor size, microscopic type, histological grade, axillary lymph node status, and molecular profile. Results:Two hundred seventeen cases, with a mean age of 62 (range: 18- 85), right breast involvement (52.53%), invasive carcinoma of no special type (86.63%), G2 histological grade (55.4%), T2 (54.41%), N+ (65.89%) and Luminal A molecular subtype (85.29%) were identified. ER, PR and AR were positive in 89.71%, 83.82% and 93.29% of cases, respectively. HER2 was overexpressed in 8.33% of cases and a high Ki67 proliferation index was present in 75% of cases. The 5-year OS was 67.2%, whereas 10-year OS was 48.5%; OS was 92.7% at 5 years and 73.8% at 10 years in axillary lymph node (LN) negative cases, while OS was 59.7% at 5 years and 41.3% at 10 years in axillary LN positive cases (p=0.003). Conclusions: Age at diagnosis ( 60 years), larger tumor size, presence of LN metastases and absence of oncological treatment are negative factors influencing prognosis, with only axillary LN status (p=0.005) and triple negative molecular profile (p=0.05) being statistically significant unfavorable independent prognostic parameters in a multivariate analysis.

Correlation between obesity and prognostic/predictive parameters with emphasis on the importance of lymph node metastases in patients with invasive breast carcinoma.

We aimed to evaluate whether obese women experience more advanced invasive breast carcinoma (IBC) with a higher number of involved lymph nodes, higher range of axillary lymph node ratio (LNR) and presence and size of extracapsular extension as it may have an impact on prognosis and management. 245 patients diagnosed with IBC were divided into normal weight (NW), overweight (OW) and obese (OB) groups. Patients were divided into high range of LNR (LNR over or equal to 0.2) and low LNR (LNR less than 0.2). The extracapsular extension dimensions were measured on the original slides of each case and grouped into ≤ 1 mm and > 1 mm. 84 patients (33.07%) were OW, 72 (29.38%) OB and 91 (37.14%) NW. 45.7% of cases had macrometastasis in the axillary lymph nodes. NW patients had significantly fewer metastatic lymph nodes (p = 0.05) than in the OW/OB groups. There was no statistically significant difference between BMI groups according to the LNR (p = 0.66). Out of 111 cases with macrometastasis, 58 cases (52.25%) had extracapsular extension (ECE) (11.7% NW, 24.32% OW and 16.22% OB). Significantly more OW patients presented extranodal invasion (p = 0.04). We found no statistically significant relationship between the extracapsular extension diameter and BMI groups (p = 0.1).

Review on Practical Approach in Multiple Breast Carcinomas: Does Each Focus Matter?

Breast carcinoma is the most frequent form of cancer encountered in women worldwide. In the routine practice, most of breast carcinomas are diagnosed as unifocal, however, a variable proportion is represented by multiple tumor foci. Since data regarding the incidence, definition, morphological and molecular profile, treatment and prognosis of multiple breast carcinomas are currently contradictory we are presenting a practical approach for pathologists dealing with such a lesion, which may display morphological and molecular heterogeneity among multiple foci with an impact on management and prognosis. Multiple tumor foci should be reported separately and taken into account when establishing the treatment.

The Impact on Survival of an Extensive Sex Cord-like Component in Mullerian Adenosarcomas: A Study Comprising 6 Cases.

Mullerian adenosarcomas are uncommon tumors of the female genital tract characterized by a synchronous proliferation of benign glands and sarcomatous stroma. In general, uterine Mullerian adenosarcomas are associated with a low risk of recurrence. The presence of "stromal overgrowth" (SO), historically defined by an estimate of the volume of sarcoma growing independently of epithelium, is associated with deep myometrial invasion, presence of heterologous elements, and poor outcomes. Very rarely, the stromal component can harbor foci resembling ovarian sex cord tumors (FROSCT). The aim of this study was to determine whether the presence of an extensive FROSCT component in Mullerian adenosarcomas has an impact on survival, akin to more typical types of SO. Six patients were included in this study. Age ranged from 39 to 71 yr. Five patients presented with uterine lesions (4 intracavitary, 1 isthmic), and 1 was located in the ovary. Tumors ranging in size from 2.5 to 19 cm were all diagnosed as Stage I. Morphologically, all had prominent FROSCT-like components that comprised 60% to 90% of tumor volume. Immunohistochemically, the FROSCT component was positive for CAM 5.2, vimentin, WT1, CD56, α-inhibin, calretinin, androgen and progesterone receptors, α-actin, and desmin. All patients are alive without disease at 26 to 102 mo. Compared with adenosarcomas with typical forms of SO, FROSCT overgrowth is low grade and not associated with recurrence or metastasis in this small series. Therefore, Mullerian adenosarcoma with extensive FROSCT should not be equated with SO.

Multifocal/multicentric breast carcinomas showing intertumoural heterogeneity: a comparison of histological tumour type and Nottingham histological grade of primary tumour and lymph node metastasis.

Our study aimed to compare the histological tumour type and Nottingham histological grade of invasive tumour foci in multifocal/multicentric breast carcinomas with those in corresponding axillary lymph node (LN) metastases. We reassessed slides from consecutive multiple breast carcinomas surgically treated with axillary LN dissection (2007-2012). 155 (19.23%) of 806 cases had multiple breast cancer, of which 115 (74.19%) cases had identical morphology. Of these, 85 (73.91%) cases had axillary LN metastases morphologically identical to the originating breast tumours. 32 of the 40 (80%) cases with different morphology had axillary LN metastases; in most heterogeneous cases with differences in grade (87.5%), the grade of metastases was identical to the grade of the tumour foci with the highest histological grade, and in 33.33% of cases the grade in LN was concordant with the grade of smaller foci. Among the 18 cases heterogeneous in histological type with axillary metastases, 33.33% presented heterogeneous histological types in LN, and 22.22% of them were only concordant with the histological type of the smaller tumour foci. The morphological aspects of axillary LN metastases correspond to the highest histological grade and/or histological tumour type with unfavourable prognosis, which does not necessarily appear in the largest tumour focus.

Genetic Profiling and Survival Outcomes in Romanian Colorectal Cancer Patients.

BACKGROUND: The increasing incidence of colorectal cancer is one of the most frequently addressed medical topics worldwide. It represents the third most commonly diagnosed cancer in both men and women globally, with significant implications for public health. Mortality for this type of malignancy remains high, second only to lung cancer. Given their clinical relevance, the identification and understanding of KRAS and BRAF mutations have become crucial components of personalized medicine approaches in colorectal cancer. Hence, our desire is to carry out a research that analyzes the impact of these mutations in terms of survival and mortality on patients diagnosed with colorectal cancer. METHODS: We conducted a retrospective study spanning from 2018 to 2022, which involved 118 patients diagnosed with colorectal cancer. The patients were selected from the databases of the Oradea County Emergency Clinical Hospital and Pelican Oradea Hospital. Genetic testing was performed at the "Resident Laboratory" clinic. Subsequently, patients were divided into two groups of equal size based on the presence or absence of mutations. RESULTS: The survival rate one year after the diagnosis of colorectal cancer is 84.74% (N=50/59) for the mutant group versus 67.96% (N=40/59) for the wild-type group. The survival rate at five years from the diagnosis of colorectal cancer is 25.93% (N=15/59) for patients with wild-type tumors compared to 33.54% (N=20/59) for patients with tumors with mutant status (p=0.483, HR=1.153, CI 95% 0.7661-1.735). The five-year survival rate, depending on the mutation present, highlights the fact that the average overall survival for those with the KRAS mutation is 38.6 months (CI 95% 35.22-41.97) and for those with the BRAF mutation is 8.3 months (CI 95% 5.42-11.17) (p=0.039). The mortality rate for mutant KRAS is 44.89% (N=22/50), while for those with mutant BRAF, it is 100% (N=6/6). CONCLUSIONS: We observed no statistically significant difference in overall survival rate and disease-free interval between the two studied groups, but the overall survival was better for those with mutations present (38.64 months versus 31.07 months for wild-type tumors). The mortality rate is higher among tumors with wild-type status (p=0.005), in the first year after the diagnosis of colorectal cancer. The BRAF mutation confers a much worse prognosis than the KRAS mutation, from both the survival analysis and the mortality rate.

mTOR Pathway Activation Assessed by Immunohistochemistry in Cervical Biopsies of HPV-associated Endocervical Adenocarcinomas (HPVA): Correlation With Silva Invasion Patterns.

The Silva pattern of invasion, recently introduced to stratify patients at risk for lymph node metastases in human papillomavirus-associated endocervical adenocarcinomas (HPVAs), can only be assessed in cone and loop electrosurgical excision procedure excisions with negative margins or in a hysterectomy specimen. Previous studies found associations between destructive stromal invasion patterns (Silva patterns B and C) and mutations in genes involved in the MEK/PI3K pathways that activate the mammalian target of rapamycin (mTOR) pathway. The primary aim of this study was to use cervical biopsies to determine whether markers of mTOR pathway activation associate with aggressive invasion patterns in matched excision specimens. The status of the markers in small biopsy specimens should allow us to predict the final and biologically relevant pattern of invasion in a resection specimen. Being able to predict the final pattern of invasion is important, since prediction as Silva A, for example, might encourage conservative clinical management. If the pattern in the resection specimen is B with lymphovascular invasion or C, further surgery can be performed 34 HPVA biopsies were evaluated for expression of pS6, pERK, and HIF1α. Immunohistochemical stains were scored semiquantitatively, ranging from 0 to 4+ with scores 2 to 4+ considered positive, and Silva pattern was determined in follow-up excisional specimens. Silva patterns recognized in excisional specimens were distributed as follows: pattern A (n=8), pattern B (n=4), and pattern C (n=22). Statistically significant associations were found comparing pS6 and pERK immunohistochemistry with Silva pattern (P=0.034 and 0.05, respectively). Of the 3 markers tested, pERK was the most powerful for distinguishing between pattern A and patterns B and C (P=0.026; odds ratio: 6.75, 95% confidence interval: 1.111-41.001). Although the negative predictive values were disappointing, the positive predictive values were encouraging: 90% for pERK, 88% for pS6 and 100% for HIF1α. mTOR pathway activation assessed by immunohistochemistry in cervical biopsies of HPVA correlate with Silva invasion patterns.

Invasive Stratified Mucinous Carcinoma (iSMC) of the Cervix Often Presents With High-risk Features That Are Determinants of Poor Outcome: An International Multicenter Study.

Invasive stratified mucinous carcinoma (iSMC) has been suggested to represent an aggressive subtype of endocervical adenocarcinoma. We sought to investigate the outcomes of iSMC and determine which clinical and pathologic parameters may influence the prognosis. Slides from 52 cases of iSMC were collected and classified as follows: pure iSMC (>90% of the entire tumor) and iSMC mixed with other human papillomavirus-associated adenocarcinoma components (miSMC) (>10%, but <90% of the entire tumor). Clinical and pathologic parameters were evaluated and compared with overall survival (OS) and recurrence-free survival (RFS). One third of patients with iSMC presented with lymph node metastases (LNM) and 25% developed local recurrences, whereas 4 (7.7%) developed distant recurrences. 29 cases (55.8%) were pure iSMC, whereas 23 cases (44.23%) were miSMC. OS was 74.7% in pure iSMC versus 85.2% in miSMC (P=0.287). RFS was 56.5% in pure iSMC and 72.9% in miSMC (P=0.185). At 5 years, OS in stage I was 88.9% versus stage II to IV 30% (P=0.004), whereas RFS in stage I was 73.9% versus stage II to IV 38.1% (P=0.02). OS was influenced by International Federation of Gynecology and Obstetrics (FIGO) stage (P=0.013), tumor size (P=0.02), LNM (P=0.015), and local recurrence (P=0.022), whereas RFS was influenced by FIGO stage (P=0.031), tumor size (P=0.001), local recurrence (P=0.009), LNM (P=0.008), and type of surgical treatment (P=0.044). iSMC is an aggressive cervical tumor biologically different from other human papillomavirus-associated adenocarcinomas due to the propensity for LNM, local/distant recurrence. FIGO stage, tumor size, LNM, and presence of local/pelvic recurrences are determinants of outcome in iSMCs.

Discordance Rate in Estrogen Receptor, Progesterone Receptor, HER2 Status, and Ki67 Index Between Primary Unifocal and Multiple Homogenous Breast Carcinomas and Synchronous Axillary Lymph Node Metastases Have an Impact on Therapeutic Decision.

BACKGROUND: We aimed to demonstrate that in breast carcinomas the tumor profile is not stable during the metastatic process, with impact on therapeutic decisions. MATERIALS AND METHODS: We analyzed the estrogen receptor (ER), progesterone receptor (PR), and HER2 status and Ki67 index in 41 primary unifocal (PU) and 37 primary multiple (PM) breast carcinomas with identical immunohistochemical profiles among multiple tumor foci and the matched axillary lymph node metastases. We defined as concordant cases in which the primary tumor (PU or PM) and lymph node metastases displayed identical positivity or negativity for ER, PR, HER2, Ki67 and as discordant cases in which there was a mismatch in at least 1 biological parameter among PU and PM tumor and lymph node metastases. Moreover, we defined as concordant cases in which the molecular profile (based on the immunohistochemical evaluation of ER, PR, HER2, and Ki67) was concordant among PU and PM tumors and lymph node metastases and mismatch cases as those in which the molecular profile of the primary tumor differs from one of the lymph node metastases in at least 1 lymph node. RESULTS: The positivity for the biological markers is not stable during the metastatic process. In this study the total rate of discordant cases was 92.7% in PU tumors and 75.7% in PM homogenous tumors (P=0.058, odds ratio=0.245, 95% confidence interval, 0.06-0.991). The total rate of shifted cases was 64.9% in PM tumors and 82.9% in PU tumors. The highest rate of shifting was encountered from Luminal B-like to Luminal A-like. In 11 out of 37 (29.7%) PM and in 17 out of 41 (41.5%) PU cases the subtype shifted to a poorer one with respect to prognosis. CONCLUSIONS: The patients in whom the primary tumor is hormone receptor and/or HER2 negative but is positive for these markers in the axillary lymph nodes could become eligible for hormonal treatment and/or trastuzumab treatment, which may significantly improve the patient's outcome.

Intratumoral Heterogeneity for Ki-67 Index in Invasive Breast Carcinoma: A Study on 131 Consecutive Cases.

INTRODUCTION: In addition to conventional histopathologic parameters, the assessment of proliferation is a major factor in treatment decision in breast carcinoma patients. The aim of this study was to assess whether Ki-67 heterogeneity in invasive breast carcinomas could have an impact over treatment decision. MATERIALS AND METHODS: Immunohistochemistry for Ki-67 was evaluated in resection specimens of 131 consecutive invasive breast carcinomas. Heterogeneity was defined as the presence of a low (<17%) and high (>35%) proliferative activity within the same tumor in the same histologic section. The rest of the cases were defined as homogenous. Clinical-pathologic features were also analyzed. RESULTS: A total of 107 (81.67%) of the cases were homogenous and 24 of 131 cases (18.32%) showed heterogeneity as defined above. Among these, 10 (41.6%) cases showed a gradient of increasing staining toward the tumor edge and 14 (58.4%) cases showed hot spots. In general, the proliferative activity varied from 1% to 90% in different areas of the tumor. A higher incidence of breast carcinoma was observed after menopause in both groups (83.33% in heterogeneous cases and 79.43% in homogeneous cases) (P=0.783). These groups were similar as far as the most frequent histologic types were concerned: no special type (95.83% vs. 56.07%) (P=0.0001). Tumor histologic grade, T and N stage were similar in both groups. We noted a higher proportion of stage N3 cases in the heterogeneous tumor group (54.16% vs. 34.57%) (P=0.14). Prognostic markers analysis in the heterogeneous cases revealed 100% positivity for hormone receptors (compared with 94.65%) and a much higher proportion of HER2-negative cases (87.5% vs. 73.83%) (P=0.19). CONCLUSION: As Ki-67 heterogeneity can be encountered in breast carcinomas and Ki-67 value could have an impact on clinical decisions, it is mandatory to evaluate the whole specimen and not only the core biopsy specimen and to correlate it with mitotic count.

Clinical implications of multifocality as a prognostic factor in breast carcinoma - a multivariate analysis study comprising 460 cases.

BACKGROUND: Multifocality is not listed among prognostic factors in international breast cancer guidelines. This study aims to analyze survival in multiple breast carcinomas (MFMC cc) compared to unifocal ones (UF cc), in order to assess the prognostic impact of multifocality. METHODS: The study included 460 breast carcinomas (2002-2006) with a median follow-up time of 104 months (74-134 months). We assessed mortality rates, overall survival at 5 years and 10 years in general, overall survival at 5 and 10 years in MFMC cc compared to UF cc, as well as median survival and survival rate according to age, T status and axillary lymph node status in MFMC cc compared to UF cc. We carried out a multivariate analysis in order to identify independent predictor factors for survival. RESULTS: 69/460 (15%) of cases were MFMC cc. Mortality rates were 56.5% in MFMC cc versus 45.1% (UF cc) (P = 0.08). 5-year overall survival was 55.9% in MFMC cc vs. 64.7% UF cc, and the 10-year overall survival was 34.9% MFMC cc vs. 52.7% UF cc (P = 0.27). Median survival in MFMC cc was 78 months (6.5 years), whereas in UF cc it was 126 months (10.5 years). However, in the multivariate analysis, survival was independently influenced only by tumor size and the presence of axillary lymph node metastases (P < 0.0001). CONCLUSION: Breast cancer multifocality is associated with higher general mortality rates, lower 5 and 10-year overall survival, yields a lower median survival, but it does not constitute an independent prognostic factor in multivariate analysis.

Morphologic and molecular subtype status of individual tumor foci in multiple breast carcinoma. A study of 155 cases with analysis of 463 tumor foci.

The aim of this study is to evaluate biomarker immunophenotypic heterogeneity between separate tumor foci of multiple breast carcinoma, its correlation with morphologic features and tumor grade, and its influence on the treatment. One hundred fifty-five invasive multiple breast carcinomas were retrospectively analyzed over a 6-year period (2007-2012), and the expression of estrogen (ER) and progesterone (PR) receptors, Ki-67 proliferative index, human epidermal growth factor receptor 2 expression, morphologic subtype, and tumor grading were analyzed in each tumor focus. We found mismatches in immunohistochemical features in 71 (53.78%) of 132 patients with similar histology and in 13 (56.52%) of 23 cases with different histology. When analyzing mismatches in ER and PR statuses together, in 4 (23.52%) of 17 cases, one of the tumor foci was ER or PR positive, whereas the index tumor did not express either marker. The most numerous mismatches (45 cases; 29.03%) concerned the proliferative index; in 14 cases (9.03%), the additional focus had a higher index than did the main focus, and in 9 of these cases, the additional focus displayed a histologic grade of 3. Mismatches in human epidermal growth factor receptor 2 status appeared in 25 (16.12%) cases. The histologic type of the additional foci was different from the index tumor in 23 (14.83%) cases. Assessment of all tumor foci would have determined 19 (12.25%) cases to receive different adjuvant treatments compared with what would have been indicated if only the biological status of the largest primary tumor was assessed. We strongly recommend assessing and reporting each tumor focus independently.

Case report: Papillary mesothelioma of the peritoneum with foamy cell lining.

A 34-year-old female, with a history of continued asbestos exposure, presented with a papillary peritoneal mesothelioma with a diffuse, prominent clear foamy cell change, with microvacuolation in its papillary lining, that expressed cytokeratins 7, 5/6 and calretinin as well as nuclear WT-1 and apical membrane staining for thrombomodulin, podoplanin D2-40 and HBME-1. In contrast, lining cells were CD68 negative. Foamy cell change has been reported in isolated cases as solid cords but not as a diffuse change in the mesothelial papillary lining. This phenomenon prompts differential diagnoses with abdominal and renal papillary clear cell tumours, which were discarded after a characteristic mesothelial immunophenotype was demonstrated. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/4679576081031834.

Morphological heterogeneity of the simultaneous ipsilateral invasive tumor foci in breast carcinoma: a retrospective study of 418 cases of carcinomas.

The aim of this paper was to assess whether the morphological appearance (i.e. histological tumor type and histological grade) of simultaneous invasive breast carcinoma foci is heterogeneous, since it is known that adjuvant therapy is established according to these parameters. Patients with simultaneous breast tumors in which only the features of the largest neoplastic focus are reported could thus be undertreated. A retrospective study of 418 cases of breast carcinomas was conducted over a 3-year period. The histological tumor types and histological grades of multifocal/multicentric carcinomas in each tumor focus were compared, and mismatches among foci were recorded. Ninety-one of the 418 cases reviewed had multiple carcinomas (21.77%). A comparison between multiple synchronous tumor foci revealed that their histological type was different in 12.08% of the cases. Mismatches among foci were also observed in 9.89% of the cases when evaluating the histological grade, and 5 out of 9 additional tumor foci with a different grade from the largest (index) tumor (55.55%) displayed a higher grade compared to the index tumor. Since the histological tumor type and histological grade of the individual foci may vary considerably within the same tumor and the additional foci may be of higher grade than the index tumor, we believe that reporting morphologic parameters with more unfavorable characteristics in addition to the parameters of the index tumor is imperative.