Prognostic Role of Tumoral PD-L1 and IDO1 Expression, and Intratumoral CD8+ and FoxP3+ Lymphocyte Infiltrates in 132 Primary Cutaneous Merkel Cell Carcinomas.

The association of immune markers and clinicopathologic features and patient outcome has not been extensively studied in Merkel cell carcinoma (MCC). We correlated tumoral PD-L1 and IDO1 expression, and intratumoral CD8+ and FoxP3+ lymphocytes count with clinicopathologic variables, Merkel cell polyomavirus (MCPyV) status, and patient outcomes in a series of 132 MCC. By univariate analyses, tumoral PD-L1 expression >1% and combined tumoral PD-L1 >1% and high intratumoral FoxP3+ lymphocyte count correlated with improved overall survival (OS) (p = 0.016, 0.0072), MCC-specific survival (MSS) (p = 0.019, 0.017), and progression-free survival (PFS) (p = 0.043, 0.004, respectively). High intratumoral CD8+ and FoxP3+ lymphocyte count correlated with longer MSS (p = 0.036) and improved PFS (p = 0.047), respectively. Ulceration correlated with worse OS and worse MSS. Age, male gender, and higher stage (3 and 4) significantly correlated with worse survival. MCPyV positivity correlated with immune response. By multivariate analyses, only ulceration and age remained as independent predictors of worse OS; gender and stage remained for shorter PFS. Tumoral PD-L1 expression and increased density of intratumoral CD8+ lymphocytes and FoxP+ lymphocytes may represent favorable prognosticators in a subset of MCCs. Tumoral PD-L1 expression correlated with intratumoral CD8+ and FoxP3+ lymphocytes, which is supportive of an adaptive immune response.

Systematic Review of Second Primary Oropharyngeal Cancers in Patients With p16+ Oropharyngeal Cancer.

OBJECTIVE: To systematically review the literature to determine the prevalence and clinical outcomes of second primary oropharyngeal squamous cell carcinoma (OPSCC). DATA SOURCES: Search strategies created with a medical librarian were implemented using multiple databases in October 2019. REVIEW METHODS: The population of interest included adults age >18 years with a p16+ or human papillomavirus-positive OPSCC. The outcome was a synchronous or metachronous second primary OPSCC. Inclusion and exclusion criteria were designed to capture all study designs. In total, 685 records were identified by the search strategy. Two reviewers independently performed the review, extracted data, and performed a quality assessment. Primary Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. A random-effects model was used for the meta-analysis. RESULTS: A total of 2470 patients with 35 second primary OPSCCs from 15 studies were identified. The pooled prevalence of second primary OPSCC was 1.4% (range, 0%-14.3%). In the random-effects model, the prevalence was estimated at 1.3% (95% CI, 0.7%-2.3%; P = .51, I2 = 52%). Of the 30 patients with treatment information, 26 (86.7%) received surgical treatment, while 4 (13.3%) underwent nonsurgical therapy. Of the 29 patients with available survival information, 22 (75.9%) had no evidence of disease at last follow-up, 5 (17.2%) ultimately died of disease, and 2 (6.9%) were alive with disease. CONCLUSION: Overall, the rate of second primary OPSCC in patients with an index p16+ OPSCC is low, and most patients are successfully treated. Insufficient evidence currently exists to recommend routine elective tonsillectomy during surgical treatment of p16+ OPSCC.

[Hepatic epithelioid angiomyolipoma/PEComa and focal nodular hyperplasia in a patient with a previous history of cutaneous melanoma]. / Angiomiolipoma epitelioide/PEComa hepático e hiperplasia nodular focal en una paciente con antecedentes de melanoma cutáneo.

Hepatic perivascular epithelioid cell tumors (PEComas) are uncommon mesenchymal neoplasms. PEComas concurrent with other hepatic lesions is a very rare occurrence, with only two previously reported cases. We report a primary hepatic PEComa associated with focal nodular hyperplasia in a patient with a previous history of cutaneous melanoma. Diagnostic imaging studies suggested a hepatic adenoma and the patient underwent a segmentectomy. The tumor was mainly composed of epithelioid cells, adipose tissue and smooth muscle fibers intermixed with blood vessels. The neoplastic cells were diffusely immunoreactive for HMB-45, Melan-A and smooth muscle actin, but not for Hepatocyte, S100, MITF or BRAF. Molecular studies were negative for BRAFV600 mutation. The final diagnosis was hepatic epithelioid angiomyolipoma/PEComa. The differential diagnosis of hepatic PEComa is discussed.

Intravascular Colonization of Kaposi Sarcoma: Expanding the Spectrum of Specific Infiltrates of B-Cell Chronic Lymphocytic Leukemia.

B-cell chronic lymphocytic leukemia (CLL), a low-grade malignancy consisting of CD5(+), CD23(+), and CD43(+) small B lymphocytes, is the most frequent leukemia in the western world. Patients with CLL may exhibit skin changes characterized by histopathologic evidence of infiltration by atypical B lymphocytes, also known as "specific cutaneous infiltrates of CLL"; in addition, CLL is known to be associated with an increased risk of second cancers, including Kaposi sarcoma (KS). The combination of KS and CLL within the same cutaneous biopsy specimen has only rarely been described. We report a peculiar case of KS occurring in a patient with CLL, in which histopathological evaluation of KS lesions revealed prominent accumulation of CLL lymphocytes within neoplastic vascular spaces. We believe that our findings represent a novel example of intravascular colonization of vascular neoplasms by neoplastic lymphoid cells, further expanding the evergrowing spectrum of specific cutaneous infiltrates of CLL.

Pancreatic cancer arising in the remnant pancreas is not always a relapse of the preceding primary.

This study aimed to understand the biology of pancreatic ductal adenocarcinoma that arises in the remnant pancreas after surgical resection of a primary pancreatic ductal adenocarcinoma, using integrated histological and molecular analysis. Patients who underwent a completion pancreatectomy for local recurrence following resection of a primary pancreatic ductal adenocarcinoma were studied with histological analysis and next-generation sequencing of the primary and the recurrent cancer. Of six patients that met the inclusion criteria, three cases were classified as "true" recurrences, i.e., the primary and the cancer in the remnant pancreas shared both morphological features and molecular alterations. Two cases were identified as having independent cancers that exhibited different histological and molecular profiles. In the remaining case, the relationship could not be determined. Pancreatic ductal adenocarcinoma that arises in the remnant pancreas can be either a second primary or a "true" relapse of the preceding primary. The differentiation of second primaries from local recurrences may have important implications for patient management.

Factors related to colorectal cancer in advanced adenomas and serrated polyps: a further step toward individualized surveillance.

AIM: The risk of presenting synchronous or metachronous neoplasm, either adenoma or carcinoma, increases after an initial colonic lesion develops. It is known as tumor multicentricity and constitutes the rationale for surveillance programs. This study was designed to identify the clinical, pathologic, and molecular features related to previous or synchronous colorectal cancer (CRC) in patients with advanced adenomas (AA) or serrated polyps (SP). PATIENTS AND METHODS: We carried out a prospective analysis of 4143 colonoscopies performed at our medical department between 1 September 2014 and 30 September 2015. Patients with AA/SP associated with previous or synchronous CRC are compared with patients with solitary AA/SP. We also performed immunohistochemical for the mismatch repair proteins in 120 AA or SP, 60 of them related to CRC. RESULTS: Three-hundred and seventy-nine AA or SP were removed. Among these, 66 (17.3%) were associated with a previous (n=31) or synchronous CRC (n=35). Age older than or equal to 65 years (odds ratio: 1.15, 95% confidence interval: 1.05-1.26, P=0.002) and male sex (odds ratio: 2.13, 95% confidence interval: 1.3-3.49, P=0.003) were found to be independent predictive factors for CRC in patients with AA/SP by multivariate analysis. Only one of the 120 AA/SP available for immunohistochemical testing showed loss of staining and it was not related to CRC. CONCLUSION: In patients with AA or SP, it is possible to identify a subgroup that is more likely to be associated with CRC and then prone to tumor multicentricity. These results have potential implications for establishing criteria for a more targeted surveillance.

[Low-grade eosinophilic unclassified renal cell carcinoma, a recently proposed entity in the spectrum of eosinophilic renal cells tumors: Report of one case and discussion]. / Le carcinome rénal inclassé de bas grade à cellules éosinophiles, une entité récemment proposée dans le spectre des tumeurs rénales à cellules éosinophiles : étude d'un cas et discussion.

Low-grade eosinophilic unclassified renal cell carcinoma is a rare kidney tumor recently described, not included in the WHO classification, which is very close to oncocytoma. It is unknown to most pathologists and clinicians. From a histopathological point of view, this tumor is composed of oncocytic cells arranged in a diffuse and solid pattern, without cell nests, that makes it possible to differentiate it from oncocytoma, and expresses cytokeratin 7 (CK7) heterogeneously. We report a case with a cranial vault metastasis, and present the features to differentiate this entity from oncocytoma. Furthemore, we discuss about unclassified renal cell carcinomas with oncocytic cells.

Incidentally detected pancreatic neuroendocrine microadenoma with lymph node metastasis.

Pancreatic neuroendocrine microadenomas (NEMAs) are non-functioning neuroendocrine tumors < 0.5 cm with a low proliferation rate and are considered benign. We report on a pancreatic NEMA with lymph node metastasis. A male in his 70s had pylorus-preserving pancreaticoduodenectomy for a distal bile duct carcinoma, which was a 2.1 cm well-differentiated-infiltrating adenocarcinoma with invasion limited to the bile duct wall. An incidental separate 0.4 cm well-differentiated NEMA was found in the pancreatic head with metastatic well-differentiated neuroendocrine tumor in one peripancreatic lymph node. Both neuroendocrine tumors in the pancreatic head and in the lymph node were composed of nests of uniform neoplastic cells with a fine chromatin pattern. The Ki-67 labeling index of NEMA was 0.85%. The neoplastic neuroendocrine cells in both the pancreas and node were diffusely positive for synaptophysin, chromogranin, and insulin. Therefore, this unusual case provides an exception to the current classification system which regards NEMAs as benign lesions.

Comparative clinicopathological and cytomorphological analyses of peritoneal carcinomatosis associated with metastatic breast carcinoma and primary peritoneal/ovarian carcinoma in patients with a history of breast carcinoma.

Causes of peritoneal carcinomatosis (PC) in patients with a history of breast carcinoma include both metastatic breast carcinoma (MBC) and primary peritoneal/ovarian carcinoma (PPOC). The origin of PC is important to determine the appropriate treatment strategy. Cytological examination of the peritoneal fluid (PF), which may be the first diagnostic approach to PC, is of distinct value in confirming the presence of malignant cells and determining the origin of PC. We analyzed the clinicopathological and cytomorphological characteristics of 33 patients with a history of breast carcinoma whose PF cytology contained malignant cells. Cases showing positive immunoreactivity for PAX8 and a lack of GATA3 expression were considered as PPOC. Sixteen patients developed PC caused by PPOC. PPOC patients were characterized by early-stage primary breast carcinoma, absence of non-peritoneal MBC before PC, and normal serum levels of CEA and CA15-3. Fourteen PPOC patients had pathogenic germline BRCA mutations. Cytological examination revealed that most of the PPOC cases had a dominant papillary arrangement of the tumor cells with severe nuclear pleomorphism, occasional bizarre nuclei, and atypical mitotic figures. Patients with PPOC who underwent cytoreductive surgery had a significantly longer survival time compared to those who did not, or MBC patients. In patients with a history of breast carcinoma presenting with PC, the presence of early-stage primary breast carcinoma, no prior non-peritoneal MBC, and a dominant papillary cellular arrangement pattern in the PF cytology were independent predictors of PPOC. Cytoreductive surgery significantly improved survival for patients with PPOC.

Are synchronous and metachronous bilateral breast cancers different? An immunohistochemical analysis focused on cell cycle regulation.

INTRODUCTION: The biology and pathomechanisms of bilateral breast cancers is not fully understood. We compared the morphological and immunohistochemical characteristics of primary tumors in patients with synchronous (sBBC) and metachronous bilateral breast cancers (mBBC), with special focus on cell cycle regulation and its correlation with markers determining intrinsic phenotype. METHODS: Immunohistochemical expression of p16Ink4A, p21(WAF1/CIP1), p27Kip1, p53, cyclin A, cyclin B, cyclin D1, cyclin D3 and cyclin E was assessed in tissue microarrays containing primary breast tumor cores from 113 mBBC and 61 sBBC. Expression of these markers was correlated with tumor grade and expression of estrogen receptor (ER), human epidermal growth factor receptor 2 (HER2) and Ki-67. RESULTS: In univariate analysis, mBBC demonstrated higher expression of p16Ink4A (both cytoplasmic: p=0.002 and nuclear: p=0.014), cyclin A (p=0.024) and B (cytoplasmic; p=0.015). In multivariate analysis mBBC were associated with lower expression of p21: p=0.038 and higher cytoplasmic expression of cyclin B: p=0.019. Lower ER expression for all BBCs and mBBC, respectively, was associated with stronger p16 expression (cytoplasmic: both p<0.000001 and nuclear: p<0.000001, p=0.00002), p53: p<0.000001, p=0.000001, cyclin A: p=0.00002, p=0.00045, cyclin B (cytoplasmic: p=0.00037, 0.00015 and nuclear: both p=0.0004) and cyclin E: p=000003, p<0.000001, and weaker expression of p27: p=0.00003, p=0.0001 and cyclin D1: both p<0.000001; for sBBC some of these correlations were absent. Higher p27 score correlated with lower HER2 expression in sBBC: p=0.018, whereas higher HER2 expression was associated with higher p53: 0.024 and cyclin E: p=0.048 expression in all BBC and higher nuclear expression of cyclin B in sBBC: p=0.027. Higher Ki-67 expression was correlated with higher expression of p16 (cytoplasmic: p=0.000015, p=0.086, p=0.0002 and nuclear: p=0.000009, p=0.016, p=0.00003) in all subsets [all BBC, sBBC (non-significant for cytoplasmic score), mBBC, respectively], p21 (all BBC: p=0.05) and sBBC: p=0.017), p53 (all BBC: p=0.0003 and mBBC: p=0.0002), cyclin A: all p<0.000001, cyclin B (cytoplasmic: p<0.000001, p=0.004, p<0.000001, respectively and nuclear: p=0.0002, p=0.047, p=0.0026, respectively), cyclin D3 (all BBC: p=0.005 and mBBC: p=0.02) and cyclin E (all BBC: p<0.000001 and mBBC: p=0.000002), and lower expression of cyclin D1 (all BBC: p=0.046 and mBBC: p=0.035) and p27 (sBBC: p=0.048). CONCLUSION: Compared to sBBC, mBBC are characterized by lower expression of p21 and higher cytoplasmic expression of cyclin B, suggesting its more aggressive behavior. Correlations between cell-cycle regulation proteins and markers of breast cancer phenotype parallel those reported for unilateral breast cancer.

Intracellular pH measured by 31 P-MR-spectroscopy might predict site of progression in recurrent glioblastoma under antiangiogenic therapy.

PURPOSE: In solid tumors, changes in the expression/activity of plasma membrane ion transporters facilitate proton efflux and enable tumor cells to maintain a higher intracellular pH (pHi ), while the microenvironment (pHe ) is commonly more acidic. This supports various tumor-promoting mechanisms. We propose that these changes in pH take place before a magnetic resonance imaging (MRI)-detectable brain tumor recurrence occurs. MATERIALS AND METHODS: We enrolled 66 patients with recurrent glioblastoma, treated with bevacizumab. Patients received a baseline and 8-week follow-up MRI including 1 H/31 P MRSI (spectroscopy) on a 3T clinical scanner, until progressive disease according to Response Assessment in Neuro-Oncology (RANO) criteria occurred. Fourteen patients showed a distant or diffuse tumor recurrence (subsequent tumor) during treatment and were therefore selected for further evaluation. At the site of the subsequent tumor, an area of interest for MRSI voxel selection was retrospectively defined on radiographically unaffected baseline MRI sequences. RESULTS: Before treatment, pHi in the area of interest (subsequent tumor) was significantly higher than pHi of the contralateral normal-appearing tissue (control; P < 0.001). It decreased at the time of best response (P = 0.06), followed by a significant increase at progression (P = 0.03; baseline mean: 7.06, median: 7.068, SD: 0.032; best response mean: 7.044, median: 7.036, SD: 0.025; progression mean: 7.08, median: 7.095, SD 0.035). Until progression, the subsequent tumor was not detectable on standard MRI sequences. The area of existing tumor responded similar, but changes were not significant (decrease P = 0.22; increase P = 0.28). CONCLUSION: Elevated pHi in radiographically unaffected tissue at baseline might precede MRI-detectable progression in patients with recurrent glioblastoma treated with bevacizumab. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2017;46:1200-1208.

Glioblastoma arising within a mediastinal mature teratoma.

Herein we present the case of a 42-year-old man who presented with an anterior mediastinal mass, which was found to represent a mature teratoma. Within it, there was a secondary somatic malignant glial neoplasm with mitotic activity and necrosis, compatible with glioblastoma. He experienced early local recurrence and lymph node metastasis, but is alive and well 3 1/2 years after diagnosis. Neither the teratoma nor the glioblastoma components had abnormalities of chromosome 12, which may implicate that this teratoma was more closely related to those arising along the midline of infants and children (type I germ cell tumor) than to the typically malignant testicular examples, which often contain mixed germ cell elements (type II germ cell tumor).

Review of a non-epithelial tumour of the small bowel after c-kit revolution.

UNLABELLED: In this article, we reviewed the case of a patient who was object, in 1999, of a published case report of schwannoma of the jejunal wall. Recently, the patient has been referred to our institution for a mass of the stomach identified by upper gastrointestinal endoscopy. The patient underwent a wedge resection of the stomach and a histopathological diagnosis of GIST of the stomach, based on a positive immunohistochemical staining of c-kit and CD34, was made. In consideration of these findings, we performed immunohistochemistry for c-kit and for CD34 on the previous lesion of the jejunal wall, which resulted strongly positive for CD117 and negative for CD34. A new diagnosis of gastrointestinal stromal tumour (GIST) of jejunal wall with moderate risk of progression was made. The lesion was also classified, according to the AJCC Seventh Edition, as a pT3, pN0, Stage II, GIST. This case shows the importance of a reassessment of the diagnosis of mesenchymal neoplasm of the small intestine made before the development of anti-CD117 antibody for a correct prognostic stratification, a better therapeutic management and a close follow-up, if necessary. KEY WORDS: Adjuvant therapy, c-kit, GIST Imatinib.

[Clinicopathological characteristics and prognostic analysis of bilateral primary breast cancer].

OBJECTIVE: The aim of this study is to explore the clinicopathological characteristics, diagnosis, multidiscipline therapy and prognosis of bilateral primary breast cancer (BPBC). METHODS: Clinical data of 133 patients with BPBC seen in Cancer Institute and Hospital of Tianjin Medical University from January 2005 to December 2008 were retrospectively analyzed and compared with those of 266 patients with unilateral primary breast cancer (UPBC). RESULTS: BPBC accounted for 2.08% of all breast cancer cases. Compared with UPBC, BPBC patients had earlier menarche, more postmenopause disease and fewer fertility(P<0.05). The T stage, pathological type, histological grade and tumor stage of the second tumor in BPBC patients were significantly different from those in UPBC cases (P<0.05). The ER and HER-2 status of both the two tumors in BPBC and the PR status of the second tumor in BPBC were also significantly different from those in UPBC(P<0.05). Besides, the menopause status when the first tumor happened and the lymph node metastasis status when the second tumor occurred were independent prognostic factors. There was no significant difference between the five-year disease free survival rates of UPBC and BPBC (79.3% and 72.8%, P>0.05), but the 5-year overall survival rates of UPBC and BPBC had significant difference(89.8% and 84.9%, P=0.02). CONCLUSIONS: The prognosis of UPBC and BPBC has significant differences. If the patient is premenopause when the first tumor occurs or had more than ten metastatic axillary lymph nodes in patient with the second one, she has a poorer prognosis. The pationts who underwent unilateral breast radical mastectomy have an increased risk of contralateral breast cancer. In order to have early detection, diagnosis and treatment, we should strengthen the follow-up of the high risk patients.

Secondary malignancies diagnosed using kidney needle core biopsies: a clinical and pathological study of 75 cases.

Involvement of the kidney by secondary malignancies is uncommon. Differentiating secondary malignancies from primary kidney/urothelial tumors can be challenging, especially on limited biopsy material. A retrospective search of our institutional archive from January 2002 to May 2015 identified 1572 cases of imaging-guided needle core biopsies of the kidney. Of these, 75 (5%) cases revealed a secondary malignancy; 48 (64%) patients had undergone the biopsy with a primary kidney tumor favored clinically. There were 39 male and 36 female patients with a mean age of 59.4 years (range, 21-83 years). The majority of the cases (n = 55, 73%) were metastases from solid tumors, with lung being the most common primary site (n = 22, 29%). Diffuse large B-cell lymphoma was the most common hematological malignancy (n = 6) secondarily involving the kidney. Radiographically, 58 (77%) cases presented as a solitary kidney mass. The primary malignancy was known prior to the kidney biopsy in 66 (88%) cases. The mean interval between diagnoses of the primary tumor and secondary involvement of the kidney was 4.5 years. Immunohistochemical stains were performed in 65 (87%) cases. Follow-up information was available for 73 patients; mean survival was 19.4 months, with 43 patients dead of their disease (mean, 12 months) and 30 patients alive at last follow-up (21 with and 9 without disease; mean, 30 months). Secondary malignancy in the kidney may clinically and pathologically mimic primary kidney tumors. Accurate diagnosis can be rendered by correlating pathological features with clinical and radiographic findings and judicious use of ancillary studies.

Hepatic adenomas with synchronous or metachronous fibrolamellar carcinomas: both are characterized by LFABP loss.

Rare hepatic adenomas are associated with synchronous or metachronous fibrolamellar carcinomas. The morphology of these adenomas has not been well described and they have not been subclassifed using the current molecular classification schema. We examined four hepatic adenomas co-occurring with or preceding a diagnosis of fibrolamellar carcinoma in three patients. On histological examination, three of the adenomas showed the typical morphology of HNF1-α inactivated adenomas, whereas one showed a myxoid adenoma morphology. All of the adenomas were negative for PRKACA rearrangements by Fluorescence in situ Hybridization (FISH) analysis. All four of the adenomas showed complete loss or significant reduction of liver fatty acid binding protein (LFABP) expression by immunohistochemistry. Interestingly, the fibrolamellar carcinomas in each case also showed loss of LFABP by immunohistochemistry. One of the fibrolamellar carcinomas was negative for PRKACA rearrangements by FISH, whereas the others were positive. To investigate if LFBAP loss is typical of fibrolamellar carcinomas in general, an additional cohort of tumors was studied (n=19). All 19 fibrolamellar carcinomas showed the expected PRKACA rearrangements and immunostains showed loss of LFABP in each case, consistent with HNF1-α inactivation. To validate this observation, mass spectrometry-based proteomics was performed on tumor-normal pairs of six fibrolamellar carcinomas and showed an average 10-fold reduction in LFABP protein levels, compared with matched normal liver tissue. In conclusion, hepatic adenomas co-occurring with fibrolamellar carcinomas show LFABP loss and are negative for PRKACA rearrangements, indicating they are genetically distinct lesions. These data also demonstrate that LFABP loss, which characterizes HNF1-α inactivation, is a consistent feature of fibrolamellar carcinoma, indicating HNF1-α inactivation is an important event in fibrolamellar carcinoma pathogenesis.

Multiple cutaneous lymphoproliferative disorders showing a retained tumor clone by T-cell receptor gene rearrangement analysis: a case series of four patients and review of the literature.

BACKGROUND: Mycosis fungoides (MF) is the most common primary cutaneous T-cell lymphoma (CTCL), followed by CD30+ lymphoproliferative disorders, including lymphomatoid papulosis (LyP) and primary cutaneous anaplastic large cell lymphoma (pcALCL). The objective was to report on a series of patients with different types of CTCL at different times in their clinical course, with a focus on clonality studies. METHODS: Four patients with multiple diagnoses of CTCLs were identified. The clinical information, treatment interventions, and histopathology were reviewed. T-cell receptor (TCR) gene rearrangement studies were performed on all available specimens. RESULTS: The four patients carried diagnoses of: (1) pcALCL and MF; (2) pcALCL, LyP, and pcALCL; (3) LyP, MF, and pcALCL; (4) LyP, pcALCL, and MF; each with characteristic presentation and histopathologic findings. The results of the TCR polymerase chain reaction showed that all tumors expressed and retained a TCR clone(s) as follows: (1) biallelic clone; (2) single clone; (3) biallelic clone with additional clone; and (4) single clone, respectively. CONCLUSION: We report a series of four cases of individual patients with coexisting diagnoses of some combination of MF, LyP, and pcALCL, whose lesions presented in nontraditional sequence and demonstrated a retained clone by gene rearrangement analysis.

Breast cancer detection among Irish BRCA1 & BRCA2 mutation carriers: a population-based study.

BACKGROUND: High-risk breast cancer screening for BRCA1/2 mutation carriers with clinical breast exam, mammography and MRI has reported sensitivity of 100 %, but BRCA1/2 mutation carriers still present with interval cancers. AIMS: We investigated the presentation and screening patterns of an Irish cohort of BRCA1/2 mutation carriers with breast cancer. MATERIALS AND METHODS: BRCA1/2 mutation carriers with breast cancer were identified in this retrospective cohort study. Records were reviewed for BRCA1/2 mutation status, demographics, screening regimen, screening modality, stage and histology at diagnosis. RESULTS: Fifty-three cases of breast cancer were diagnosed between 1968 and 2010 among 60 Irish hereditary breast ovarian cancer (HBOC) families. In 50 of 53 women, the diagnosis of breast cancer predated the identification of BRCA1/2 mutations. Breast cancer detection method was identified in 47 % of patients (n = 25): 80 % (n = 20) by clinical breast exam (CBE), 12 % by mammography (n = 3), 8 % by MRI (n = 2). Fourteen women (26 %) developed a second breast cancer. Ten of these patients (71 %) were involved in regular screening; 50 % were detected by screening mammography, 20 % by MRI and 30 % by CBE alone. Six patients (43 %) had a change in morphology from first to second breast cancers. There was no change in hormone receptor status between first and second breast cancers. CONCLUSION: In this cohort of Irish BRCA1/2 mutation carriers, compliance with screening was inconsistent. There was a 30 % incidence of interval cancers occurring in women in high-risk screening. Preventive surgery may be a more effective risk reduction strategy for certain high-risk women.