[Multicentric secretory carcinoma of the breast: Case report and review of the literature]. / Carcinoma secretor de mama multicéntrico: a propósito de un caso y revisión de la literatura.

Secretory carcinoma of the breast is a rare entity, characterized by the presence of intra- and extracellular, eosinophilic and acelular secretions. They are negative for hormone receptors and do not express human epidermal growth factor receptor HER-2/neu. However, the clinical outcome is favorable. Multicentricity is very unusual. We report a case of a 32-year-old woman with a multicentric secretory carcinoma of the breast. The main pathological features are discussed together with a review of the pertinent literature.

[SCCOHT/ovarian rhabdoid tumor: A case report]. / SCCOHT/tumeur rhabdoïde ovarienne : à propos d'un cas.

We report the case of a 22-year-old patient with acute abdominopelvic pain. The diagnosis of hypercalcemic small cell carcinoma (SCCOHT)/ovarian rhabdoid tumor has been made. Small cell carcinoma of hypercalcemic type is a rare and aggressive tumor that occurs in young women. The diagnosis of this tumor and the management must be rapid in view of its aggressiveness. Through this observation, we specify the epidemiological, diagnostic, molecular aspects and discussions about its name.

Collision of Malignant Melanoma and Squamous Cell Carcinoma in Rectum: First Report of a Rare Tumor.

The term collision tumor is used to describe two neoplasms occurring in the same anatomic location with juxtaposition of different tumor elements. Such a coexistence of tumors anywhere in the body is relatively rare. We report a case of 32-year-old female with collision tumor of rectum. The tumor showed two distinct histological patterns with predominant component consisting of malignant melanoma and a minor component of squamous cell carcinoma. The morphological picture of collision was further confirmed by specific immunohistochemical profile of the two tumors. Collision tumors of rectum are uncommon with most of the reported cases comprising adenocarcinoma and neuroendocrine tumors. To the best of our knowledge this is the first case of collision tumor of malignant melanoma and squamous cell carcinoma in the rectum.

Synchronous Cervical Minimal Deviation Adenocarcinoma, Gastric Type Adenocarcinoma and Lobular Endocervical Glandular Hyperplasia Along with STIL in Peutz-Jeghers Syndrome: Eliciting Oncogenesis Pathways.

We describe an unusual case of a Peutz-Jeghers syndrome associated with a composite synchronous cervical neoplasia comprising precursor "lobular endocervical glandular hyperplasia (LEGH)", "minimal deviation adenocarcinoma (MDA)" and "gastric-type adenocarcinoma (GTA)" along with a serous tubal intraepithelial lesion (STIL) in the right fallopian tube. A 24-year-old woman presented with a white mucoid discharge and bleeding per vaginum for one year. Histopathological evaluation showed MDA & GTA in FIGO grade III with pelvic lymph node metastasis despite a deceptively bland tumour morphology and low Ki-67 index, indicating an aggressive tumour course and poor prognosis. Diagnostic marker profile in the cervix showed gastric type mucin and positive expression of CK-7, CK-20 (patchy), CEA, and negative CDX-2, p16, ER and PR. Further an attempt at eliciting the oncogenesis pathway in view of the p16 and HPV negative nature of the gastric type cervical adenocarcinoma showed negativity for p53 but activation of cyclin D1. Growth factors including Her2 and EGFR were negative while VEGFR was over-expressed. She was treated by radical hysterectomy and pelvic radiation. She was free from recurrence at the 12-month follow-up. This is a first-time report of a STIL in the fallopian tube which was validated by a unilateral mutant type p53 expression and increased Ki67 index, associated with synchronous gastric type adenocarcinoma of the cervix in all stages of evolution.

Radiopathologic correlation of collision lung cancer with ground-glass opacity.

Pulmonary collision tumors have been described as a special entity of synchronous multiple lung cancer. There have been no reports detailing the chronological changes in primary collision lung cancers on chest computed tomography. We report a case of ground-glass lung nodules gradually colliding with each other. The collision tumors of the lung were composed of minimally invasive adenocarcinoma and adenocarcinoma in situ with epidermal growth factor mutations. Immunohistochemically, the Ki-67 labeling indices were different in the 2 components. Ki-67 staining was useful to distinguish the 2 components. The 2 dominant ground-glass tumors grew slowly with radiologic and pathologic heterogeneity.

Primary thyroid biphasic synovial sarcoma and synchronous papillary carcinoma: report of a remarkable case.

Synovial Sarcoma (SS) is the fourth most common soft tissue sarcoma, characterized by translocation t(X;18) (p11.2;q11.2). Although its histological features have been extensively described, this entity is characterized by a wide morphological spectrum so that the recognition can be very challenging at atypical anatomical localization, like the thyroid. We describe a case of a 42-ys-old female patient complaining a cervical swelling due to left intrathyroid nodule, measuring 35 mm in its greatest dimension. A Fine Needle Aspiration Cytology (FNAC) was performed and diagnosis of indeterminate neoplastic lesion, indefinite whether primary or metastatic, was formulated. After complete thyroidectomy, the histological picture of the nodule was characterized by a dual cellular population: several glandular structures composed by columnar cells with clear cytoplasm were embedded in a highly cellular stroma composed of spindle-shaped elements. Immunohistochemistry and molecular biology confirmed the morphological suspicion of SS identifying the fusion transcript SYT-SSX1 and thus ruling out several differential diagnoses which include more common thyroid malignancies. Moreover a synchronous papillary microcarcinoma was detected in the controlateral lobe.This case is noteworthy since it describes the synchronous presence in the thyroid of two completely different malignancies, the first one belonging to the soft tissue neoplasm category and the other one originating from the thyroid follicular epithelium.

Synchronous Laryngeal Squamous Cell Carcinoma and Intrahepatic Cholangiocarcinoma Present in an Obese Male with Poor Prognosis.

Concurrent laryngeal squamous cell carcinoma and intrahepatic cholangiocarcinoma is rare and no prior report has been found through a PubMed search. Here we report such a case of a 51-year old obese male presenting with hoarseness and trouble swallowing for 2 to 3 months. Imaging findings of computer tomography (CT) and magnetic resonance imaging (MRI) with and without contrast were suspicious for a T3N2 supraglottic laryngeal cancer. Laryngeal biopsy showed a well differentiated squamous cell carcinoma (SCC). As part of the evaluation of the laryngeal SCC, MRI abdomen showed an enhancing mass (4.6 cm in the greatest dimension) with diffusion restriction and capsular retraction in the right lobe of the liver. Ultrasound-guided percutaneous biopsy of the liver revealed a moderately differentiated adenocarcinoma, that was strongly and diffusely positive for CK7 and CK19, weakly positive for CDX2, and negative for HepPar 1, glypican 3, CK20, PSA and TTF1. The immunohistochemistry profile was consistent with cholangiocarcinoma. This is a unique case of laryngeal squamous cell carcinoma with concurrent cholangiocarcinoma. The prognosis was poor and the patient was placed in hospice care in two months after the diagnoses. To the best of our knowledge, this is the first documented case of synchronous laryngeal squamous cell carcinoma and intrahepatic cholangiocarcinoma. The pathogenesis, diagnosis and treatment of the diseases are discussed.

Simultaneous occurrence of splenic diffuse large B cell lymphoma and gastrointestinal stromal tumor in the stomach: a case report.

BACKGROUND: Although the primary malignant spleen tumor is relatively rare, lymphoma is the most common splenic malignancy. It can have quite different clinical manifestations that usually lead to relatively poor outcomes, and thus early and accurate diagnosis are of utmost importance. CASE PRESENTATION: The present study reports a case of a 67-year-old female with high fever, abnormal spleen (diagnosed by PET/CT) and no obvious lymph node enlargement. After being subjected to splenectomy, the patient was diagnosed with splenic diffuse large B cell lymphoma coexisting with gastrointestinal stromal tumor in the stomach. CONCLUSIONS: To our knowledge, splenic lymphoma accompanied by gastrointestinal stromal tumor in the stomach is rarely reported. This case report discusses the diagnosis and case management of a patient referring to the existing literature.

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.

Primary angiosarcoma arising in an angiomyolipoma of the kidney: case report and literature review.

BACKGROUND: Primary angiosarcoma of the kidney is a rare and aggressive malignant tumor presenting with a recognizable vascular differentiation. Its prognosis is fatal and the pathogenesis remains unclear. Renal angiomyolipoma is a relatively infrequent renal cortical neoplasm and is composed of variable proportions of adipose tissue, spindle cells, epithelioid smooth muscle cells and abnormal thick-walled blood vessels. CASE PRESENTATION: Here, we reported a case in which a 64-year-old woman presenting with the chief complaint of a progressively enlarged mass in the left abdomen. Abdominal computed tomography confirmed presence of a tumor measuring 18 cm × 11 cm in the left posterior renal fascia. Microscopic examination and immunohistochemical staining confirmed co-existence of angiomyolipoma and angiosarcoma. Furthermore, the two components interspersed with each other and there were transitional zones between them. CONCLUSIONS: In this case, we described for the first time a primary renal angiosarcoma possibly arising in a pre-existing angiomyolipoma of the kidney.

Dysplastic Lipoma: A Distinctive Atypical Lipomatous Neoplasm With Anisocytosis, Focal Nuclear Atypia, p53 Overexpression, and a Lack of MDM2 Gene Amplification by FISH; A Report of 66 Cases Demonstrating Occasional Multifocality and a Rare Association With Retinoblastoma.

In our routine and consultative pathology practices, we have repeatedly encountered an unusual subcutaneous fatty tumor with notable anisocytosis, single-cell fat necrosis, and patchy, often mild, adipocytic nuclear atypia. Because of the focal atypia, consultative cases have most often been received with concern for a diagnosis of atypical lipomatous tumor. Similar tumors have been described in small series under the designations "subcutaneous minimally atypical lipomatous tumors" and "anisometric cell lipoma." Sixty-six cases of this tumor type were collected and reviewed. Immunohistochemistry for p53, MDM2, CDK4, Retinoblastoma 1 (RB1) protein, CD34, S100, and CD163 was performed. Cases were tested for MDM2 gene amplification and RB1 gene deletion with fluorescence in situ hybridization (FISH) and for TP53 mutations by Sanger sequencing. Next-generation sequencing analysis using a panel of 271 cancer-related genes, including TP53, RB1, and MDM2, was also carried out. Our patient cohort included 57 male patients, 8 female patients, and 1 patient of unstated sex, who ranged in age from 22 to 87 years (mean: 51.2 y). All tumors were subcutaneous, with most examples occurring on the upper back, shoulders, or posterior neck (86.4%). Ten patients had multiple (2 to 5) lipomatous tumors, and the histology was confirmed to be similar in the different sites in 4 of them, including 1 patient who had a retinoblastoma diagnosed at age 1. The tumors were generally well circumscribed. At low magnification, there was notable adipocytic size variation with single-cell fat necrosis in the background associated with reactive histiocytes. Adipocytic nuclear atypia was typically patchy and characterized by chromatin coarsening, nuclear enlargement, and focal binucleation or multinucleation. Focal Lochkern change was frequent. In most instances, the degree of atypia was judged to be mild, but in 3 instances, it was more pronounced. Spindle cells were sparse or absent, and when present, cytologically bland. Thick ropy collagen bundles were absent. In all cases, p53 immunoexpression was noted (range: 2% to 20% of adipocytic nuclei), characteristically highlighting the most atypical cells. Twenty of 50 cases had MDM2 immunoreactivity, usually in <1% of the neoplastic cells, but in 4 cases, up to 10% of the cells were positive. Of 32 cases tested, 22 showed a near total loss of RB1 immunoexpression, and the remainder showed partial loss. Three of 13 cases showed RB1 gene deletion in >45% of the cells by FISH (our threshold value for reporting a positive result) with an additional 3 cases being very close to the required cutoff value. MDM2 gene amplification was absent in all 60 cases tested, including those with the greatest MDM2 immunoexpression and most pronounced atypia. All 5 tested cases showed no TP53 mutation with Sanger sequencing. Because of material quality issues, next-generation sequencing analysis could be performed in only 3 cases, and this did not reveal any recurrent mutations. All tumors were managed by simple local excision. Follow-up was available for 47 patients (range: 1 to 192 mo; mean: 27 mo) and revealed 2 local recurrences and no metastases. Dysplastic lipoma is a distinctive atypical fatty tumor variant that has p53 overexpression and RB1 gene abnormalities and lacks MDM2 gene amplification by FISH. These tumors have a strong male predominance and a notable tendency to involve the subcutaneous tissue of the shoulders, upper back and posterior neck. Multifocality is frequent (18.9% of patients with follow-up information), and there is a rare association with retinoblastoma. This tumor warrants separation from ordinary lipoma with fat necrosis, fat-rich spindle cell lipoma and the conventional form of atypical lipomatous tumor that features MDM2 gene amplification.

Expression of microRNA-145, OCT4, and SOX2 in double primary endometrioid endometrial and ovarian carcinomas.

Double primary endometrioid endometrial and ovarian carcinomas (DPEEOCs) are the most common multiple gynecological carcinomas. In recent years, gene sequential comparison analysis has strongly supported the opinion that sporadic double endometrioid endometrial and ovarian cancers (DEEOCs) are clonally related in both primary and metastatic tumors. In order to find more clonal evidence for DPEEOC, we investigated cancer stem cells (CSCs). SOX2 and OCT4 are two common factors in CSCs. MicroRNA (miRNA)-145, a small non-coding RNA, has effects in regulating gene expression and tumorigenesis in CSCs. The aim of this study was to assess the involvements of SOX2, OCT4, and miRNA-145 in the tumorigenesis of DPEEOCs. In our study, twenty DPEEOC patients were chosen. Metastatic DEEOCs and normal endometrial and ovarian tissues were also included. The expression of miRNA-145 was detected by real-time quantitative PCR. Immunohistochemical staining was used to measure the expression of OCT4 and SOX2. The results showed that miRNA-145 expression was lower in DPEEOC endometrial tissues and higher in DPEEOC ovarian tissues compared to the corresponding normal tissues. Both SOX2 and OCT4 were over-expressed in cancer tissues compared with that in normal tissues. MiRNA-145, SOX2, and OCT4 were expressed at similar levels in two cancer sites of a given DPEEOC or metastatic DEEOC sample. Besides, metastatic DEEOC sections expressed a higher level of SOX2 and OCT4 compared to the corresponding DPEEOC tissues. Together, these results support the clonality of DPEEOCs. Moreover, SOX2 and OCT4 may have some implication in DPEEOC and metastatic DEEOC diagnosis.

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.

Clinicopathologic and Molecular Characteristics of Synchronous Colorectal Carcinoma With Mismatch Repair Deficiency.

Synchronous colorectal carcinoma (CRC) is a unique disease associated with a high prevalence (∼35%) of microsatellite instability and occasionally with Lynch syndrome. The clinicopathologic and molecular features of synchronous CRC are poorly understood, particularly in Japanese patients. We examined 118 Japanese patients (236 tumors) with synchronous CRC and 117 Japanese patients (117 tumors) with solitary CRC with immunohistochemical staining for TP53 and mismatch repair (MMR) protein (MLH1, MSH2, PMS2, and MSH6) and mutation analyses of KRAS and BRAF genes. The results revealed no significant differences in clinicopathologic, histologic, and molecular findings between the synchronous and solitary CRC groups. Among the 118 synchronous CRC patients, 15 (12.7%) showed loss of MMR protein(s) expression in at least 1 tumor, whereas 103 (87.3%) showed intact expression of all 4 MMR proteins in both tumors. Of note, all patients with MMR deficiency had excellent prognoses. The 15 patients were further subdivided into 2 groups: the Concordant group, with concordant MMR loss (n=9, 7.6%) and the Discordant group, with discordant MMR loss (n=6, 5.1%). The Concordant patients showed concurrent MLH1/PMS2 loss (n=3), concurrent MSH2/MSH6 loss (n=4) and isolated MSH6 loss (n=2) in both tumors, whereas the Discordant patients showed concurrent MLH1/PMS2 loss (n=2), isolated PMS2 loss (n=2) and isolated MSH6 loss (n=2) in a single tumor. On the basis of the MMR expression pattern and BRAF mutation, the Concordant and Discordant groups were suspected to include Lynch syndrome, Lynch-like syndrome and sporadic MLH1 promoter hypermethylated CRC. In addition, KRAS mutation was present in only 1 tumor in a single patient in each group. In conclusion, the frequency of MMR protein deficiency in synchronous CRC in the Japanese population may be lower compared with the reported data from Western populations. MMR protein loss and KRAS and BRAF mutations in synchronous CRCs were heterogenous even in an individual patient.

A case of multifocal medulloblastoma in an adult patient.

Only five cases of multifocal medulloblastoma in the adult have been reported to date. We present a case in a male patient in his 50th decade of life who presented with three extra-axial lesions associated with a parenchymatous lesion of the right middle cerebellar peduncle. Sputum sample examination revealed larvae compatible with strongyloides stercoralis, which was our main differential diagnosis. Histological and immunohistochemical studies revealed the existence of a desmoplastic medulloblastoma.

Four synchronous primary cancers of the aerodigestive tract and thyroid.

We report the case of a 60-year-old man with 4 concurrent primary cancers: thyroid papillary carcinoma, esophageal squamous cell carcinoma, lung adenocarcinoma, gastric stromal tumor, and nodular goiter. A minimally invasive McKeown esophagectomy with 3-field lymph node resection played a major role in the diagnosis and resection of all primary tumors in the same sitting. Multiorgan primary cancers are not uncommon but pose challenges in diagnosis and treatment. The mechanism of development is unknown but exposure to the same carcinogens in multiple organs has been implicated.

L1CAM expression associates with poor outcome in endometrioid, but not in clear cell ovarian carcinoma.

OBJECTIVE: Our aim was to study the expression of L1CAM in endometrioid and clear cell ovarian carcinomas and to evaluate its correlation with clinical parameters and patient prognosis. METHODS: Tissue microarray -based immunohistochemical analysis of L1CAM expression was performed in 249 endometrioid and 140 clear cell ovarian carcinomas. Concurrent endometrial carcinoma was found in 57 of these patients. RESULTS: L1CAM expression was found in 15% of endometrioid and 23% of clear cell ovarian carcinomas. L1CAM expression was strongly associated with poor disease-specific overall survival and poor disease-free survival in endometrioid (p<0.0001, p=0.0005), but not in clear cell ovarian carcinomas. Significant association of L1CAM expression with poor overall survival was observed in grade 1-2 carcinomas (p<0.0001), but not in grade 3 tumors. In endometrioid ovarian carcinomas, L1CAM expression was associated with aggressive tumor characteristics, such as higher grade and stage, and incomplete response to primary therapy. However, L1CAM expression was not an independent prognostic factor for overall or disease-free survival. Of the 57 patients with concurrent endometrial carcinoma L1CAM positivity was found in 4 cases both in the ovarian and endometrial tumors, and in 3 cases only in the endometrial tumor. All these seven patients with L1CAM positive tumors had poor outcome. CONCLUSIONS: L1CAM expression could serve as a biomarker for predicting clinical outcome and response to therapy in patients with endometrioid ovarian carcinoma, but not in clear cell carcinomas. L1CAM positivity also predicts poor outcome in patients with concurrent endometrioid ovarian and endometrial carcinomas.