Showing papers on "Large cell published in 2011"

Brentuximab Vedotin (SGN-35)

Abstract: Brentuximab vedotin (SGN-35) is an antibody-drug conjugate (ADC) directed against the CD30 antigen expressed on Hodgkin lymphoma and anaplastic large cell lymphoma. SGN-35 consists of the cAC10 chimerized IgG1 monoclonal antibody SGN30, modified by the addition of a valine-citrulline dipeptide linker to permit attachment of the potent inhibitor of microtubule polymerization monomethylauristatin E (MMAE). In phase II trials, SGN-35 produced response rates of 75% in patients with Hodgkin lymphoma ( n = 102) and 87% in patients with anaplastic large cell lymphoma ( n = 30). Responses to SGN-35 might be related not only to the cytotoxic effect due to release of MMAE within the malignant cell but also to other effects. First, SGN-35 may signal malignant cells through CD30 ligation to deliver an apoptotic or proliferative response. The former would amplify the cytotoxicity of MMAE. A proliferative signal delivered in the context of MMAE intoxication could enhance cell death. Second, the efficacy of SGN-35, particularly in Hodgkin lymphoma, might be attributed to its effect on the tumor microenvironment. Diffusion of free MMAE from the targeted tumor cells could result in a bystander effect that kills the normal supporting cells in close proximity to the malignant cells. The elimination of T regulatory cells that inhibit cytotoxic effector cells and elimination of cells that provide growth factor support for Hodgkin/Reed–Sternberg cells could further enhance the cytotoxic activity of SGN-35. Here we review the biology of SGN-35 and the clinical effects of SGN-35 administration. Clin Cancer Res; 17(20); 6428–36. ©2011 AACR .

Crizotinib in Anaplastic Large-Cell Lymphoma

Abstract: The anaplastic lymphoma kinase (ALK) inhibitor crizotinib has been shown to induce a response in lung cancers in which ALK is mutated. Crizotinib is also effective in anaplastic large-cell lymphoma, the tumor in which ALK rearrangement was initially detected.

Anaplastic large cell lymphoma and breast implants: a systematic review.

Abstract: Background:In recent years, there have been growing concerns about a possible association of non-Hodgkin's lymphoma—in particular, anaplastic large cell lymphoma (ALCL)—and breast implants. The purpose of this study was to identify and analyze all reported cases of non-Hodgkin's lymphoma occurring i

Immunohistochemical subtyping of nonsmall cell lung cancer not otherwise specified in fine-needle aspiration cytology: a retrospective study of 103 cases with surgical correlation.

Abstract: BACKGROUND: Histopathological subtyping of nonsmall cell lung cancer (NSCLC) is currently relevant in treatment decision because of a differential activity of specific therapeutic agents. Immunohistochemistry highlights cell differentiation lineages and, in this study, it was applied to maximize the proportion of accurately subtyped NSCLC not otherwise specified (NOS) on fine-needle aspiration cytology (FNAC) samples. METHODS: Cell blocks from 103 FNAC samples with a morphological diagnosis of NSCLC-NOS were immunostained for cytokeratin (CK) 7, CK5, TTF1, and p63, whereas p40, napsin A (Naps-A), and desmocollin-3 (DSC-3) were only assessed in a subgroup of cases with discordant (CK7 and TTF1þ for nonsquamous, CK5 and p63þ for squamous) findings. Results were correlated with surgical specimens evaluated by morphology alone. RESULTS: Thirty-seven (36%) tumors with CK7/TTF1þ and CK5/p63� corresponded to 35 cases of adenocarcinoma (ADC) and 2 cases of large cell carcinoma, whereas 9 (9%) cases with the reverse immunoprofile were squamous cell carcinoma (SQCC) at surgery (P < .001). Although the remaining 57 cases had different marker combinations, a correlation was found with ADC histology for TTF1þ samples (independent of other markers) and with SQCC for p63þ/TTF1� immunophenotype (P < .001). p40 was never expressed in p63þ ADC, whereas Naps-A was restricted to ADC and DSC-3 to SQCC lineage. The percentage of unclassified NSCLC-NOS decreased from 36% to 14%. Combinations of 2 antibodies (TTF1/DSC-3 or p63/Naps-A) in the same section allowed diagnostic optimization in scant cytological samples. CONCULSIONS: This 4-antibody panel approach may contribute to refine lung cancer classification in FNAC cell blocks, remarkably reducing the NSCLCNOS diagnostic category. Cancer 2011;000:000–000. V C 2011 American Cancer Society.

Update on precursor and early lesions of hepatocellular carcinomas.

Abstract: Context.—There is increasing evidence to support a multistep model of the process of human hepatocarcinogenesis. Precursor lesions are characterized by the appearance of dysplastic lesions in the form of microscopic dysplastic foci and macroscopic dysplastic nodules. There are 2 types of small hepatocellular carcinoma (HCC) (≤2 cm in diameter): (1) early HCC with an indistinct margin and (2) progressed HCC with a distinct margin. Pathologic diagnostic criteria for early HCC have recently been set up based on a consensus between Eastern and Western pathologists. Objective.—To review the nomenclature, pathology, and biomarkers of precursor and early lesions of HCC. Data Sources.—Literature review and illustrations from case materials were used. Conclusions.—Dysplastic foci are composed of large and small cell changes. Small cell change is considered to be a more advanced precursor lesion than large cell change, and large cell change is a rather heterogeneous lesion that may represent both reactive ...

Anaplastic large T-cell lymphoma and breast implants: a review of the literature.

Abstract: Background:Anecdotal reports and one case-control study suggested an association, without evidence of causation, between breast implants and anaplastic lymphoma kinase–negative anaplastic large T-cell lymphoma (ALCL), a rare non-Hodgkin's lymphoma. This review summarizes the published evidence, incl

Breast implant-associated, ALK-negative, T-cell, anaplastic, large-cell lymphoma: establishment and characterization of a model cell line (TLBR-1) for this newly emerging clinical entity.

Abstract: Primary breast lymphoma after breast prostheses placement has previously been reported, and a survey of the literature from the past 30 years has identified sporadic reports of 5–11 cases of primary breast non-Hodgkin lymphoma (NHL) arising in patients with saline or silicone breast implants.1–6 Several previous meta-analyses evaluating the risk of neoplasia associated with breast prostheses provided conflicting results or did not exclude patients with a previous breast malignancy, and, thus, the question remains to be answered definitively.7,8 Brody et al9 recently identified 40 cases of breast implant-associated primary breast NHL of T-cell type occurring in patients with a specific type of textured breast prostheses. This case series is remarkable for the large number of patients identified and the similarity in patient presentation and disease. Primary non-Hodgkin lymphoma (NHL) of the breast is rare (900 incident cases reported annually; 0.5% of all breast malignancies), and the vast majority have a B-cell phenotype.1,9 In the series reported by Brody et al, 9 all cases have been classified as T-cell, anaplastic, primary, breast non-Hodgkin lymphomas, an exceedingly rare diagnosis. The reported cases also share a similar presentation, clinical course, and implant style.9 The initial presentation for these patients (average age 44.7 years; range, 33–87 years) was late peri-implant seroma, severe capsular contracture, or pericapsular tumor mass, with an average time from implant of 5.8 years (range, 1–20 years).9 The clinical course of the malignancy was typically benign. Patients received surgical treatment, chemotherapy, and/or radio-therapy, and except for 1 patient, remain disease free.9 Implant information was available for 25 of 40 patients, and 23 of 25 shared a common lost-salt method of the textured shell.9 In this series, both silicone-gel and saline-filled implants were involved.9 Although previous reports have not conclusively shown an increased risk of primary breast NHL with silicone-gel or saline implants,7,8 this recent series arising in textured salt-withdrawal breast implants may represent a subset of patients with an increased risk of malignancy. Anaplastic large-cell lymphoma (ALCL) was first described by Stein et al10 in 1985 as a rare T- or null-cell NHL characterized by large, anaplastic, lymphoid cells with strong uniform CD30 expression. ALCL accounts for 3% of adult NHL and may involve nodal or extranodal sites.5 Several subclassifications of ALCL exist: systemic, secondary, and primary cutaneous (pc-) ALCL. Roden et al6 have also suggested seroma-associated (sa-) ALCL as a clinical entity related to pc-ALCL and occurring adjacent to breast implants. These 4 lymphomas are histologically indistinguishable, consisting of pleomorphic epithelioid tumor cells with blast-like appearance, severe cellular and nuclear atypia, and large nuclei and nucleoli.11,12 However, these diagnoses represent distinct clinical entities.12–13 Systemic and secondary ALCL are characterized by an aggressive clinical course and frequently express anaplastic large-cell kinase (ALK) subsequent to a reciprocal t(2;5) translocation fusing the nucleophosmin (NPM1) and ALK genes.4,11–13 In contrast, pc- and sa-ALCL are indolent malignancies that rarely carry the t(2;5) translocation and are usually ALK-negative.14 Most cases of CD30+ ALK-negative, sa-, or pc-ALCL present as solitary or regional nodules and/or tumors showing ulceration, with extracutaneous or regional lymph node involvement seen in only 10% of patients.14 The preferred treatment for pc- or sa-ALCL is localized radiation or surgical excision, with systemic chemotherapy reserved for cases with large tumor burden and extracutaneous involvement.12 Other features reported in ALK-negative ALCL include T-cell markers, cytotoxic phenotype (perforin+, granzyme B+, TIA+), activation and antigen-presentation antigens (eg, CD25, HLA-DR, CD80, CD86), CD56, and transferrin receptor CD71.15–17 T-cell neoplasms usually demonstrate clonal TCRγ gene rearrangement, but up to 10% of ALCL neoplasms also show rearrangement of the immunoglobulin heavy-chain (IgH) gene.18 Aberrant expression of cell-cycle genes and embryonic transcription factor Notch1 can contribute to malignant transformation in lymphoma, as well as overexpression of T-cell specific genes TAL1, HOX11, LYL1, and LMO1/2.19,20 This article describes the case presentation of a primary, breast, T-cell, ALK-negative ALCL in a patient with cosmetic textured (lost-salt) breast implants from the series reported by Brody et al9 A model cell line, T-cell lymphoma breast-1 (TLBR-1), was established from the primary tumor tissue and recapitulates the phenotype and cytogenetics of the original tumor. This cell line has been made available for others in the scientific community through the American Tissue-Type Cell Collection (ATCC; www.atcc.org) and represents an important model for further studies of this disease.

Neuroendocrine prostate cancer xenografts with large‐cell and small‐cell features derived from a single patient's tumor: Morphological, immunohistochemical, and gene expression profiles

Abstract: BACKGROUND Small-cell carcinoma (SCC) of the prostate is an AR-negative variant of prostate cancer found at progression in 10–20% of castrate-resistant disease. Its finding predicts a distinct clinical course and a poor prognosis. Large-cell neuroendocrine carcinoma (LCNEC) is a much rarer variant that behaves similarly to SCC. The biological mechanisms that drive these disease variants are poorly understood. METHODS Eight tumor fragments from the salvage pelvic exenteration specimen of a patient with castrate-resistant prostate carcinoma were subcutaneously implanted into 6- to 8-week-old male CB17 SCID mice. Serial tissue sections and tissue microarrays of the resulting MDA PCa 144 xenograft lines were used for histopathologic and immunohistochemical characterization of the xenografts and their tissue of origin. RNA from two representative xenograft sublines was used for gene-expression profiling. RESULTS All eight fragments formed tumors: four of the MDA PCa 144 xenograft sublines had morphologic characteristics of SCC and four, of LCNEC. All retained high fidelity to their parent tumor tissue, which remained stable through serial passages. Morphological transitions in the specimen of origin suggested LCNEC represents an intermediate step between adenocarcinoma and SCC. Over 2,500 genes were differentially expressed between the SCC (MDA PCa 144-13) and the LCNEC (MDA PCa 144-4) sublines and enriched in “Nervous System Development” Gene Ontology subtree. CONCLUSION The eight xenograft models described represent the spectrum of neuroendocrine carcinomas in prostate cancer and will be valuable preclinical tools to study the pathogenesis of and therapy targets for this increasingly recognized subset of lethal prostate cancer. Prostate 71:846–856, 2011. © 2010 Wiley-Liss, Inc.

Class II major histocompatibility complex expression and cell size independently predict survival in canine B-cell lymphoma.

Abstract: Background: Class II major histocompatibility complex (MHC) is an independent predictor of outcome in human B-cell lymphoma. We assessed class II expression together with other markers for their impact on prognosis in canine B-cell lymphoma. Hypothesis: Low class II MHC expression, large cell size, and expression of CD34 will predict a poorer outcome in canine B-cell lymphoma. Expression of CD5 and CD21 on tumor cells also may be associated with outcome. Animals: One hundred and sixty dogs with cytologically confirmed lymphoma. Methods: Patient signalment, treatment type, and flow cytometry characteristics were analyzed for their influence on outcome. A multivariable predictive model of survival was generated using 2/3 of the patients and validated on the remaining 1/3 of the dataset. Results: Class II MHC expression had a negative association with mortality and relapse. Treatment type also influenced relapse and mortality, whereas cell size and patient age was only associated with mortality. CD34, CD21, and CD5 expression was not associated with disease outcome. The constructed model performed variably in predicting the validation group's outcome at the 6-month time point. Conclusions and Clinical Importance: Low levels of class II MHC expression on B-cell lymphoma predict a poor outcome, as in human B-cell lymphoma. This finding has implications for the use of dogs to model human lymphomas. Class II expression, cell size, treatment, and age can be combined to predict mortality with a high level of specificity.

The morphological and molecular diagnosis of lung cancer.

Abstract: Lung cancer is responsible for 14.2% of neoplasms in men and 7.4% in women; it is the third most common cancer in Germany. In terms of mortality, however, it is in first place: 25.7% of male cancer patients (1st place) and 12.1% of female cancer patients (3rd place) die due to lung cancer. The reasons include the aggressiveness of the tumor and its strong tendency to metastasize. The current 5-year survival rates for men are 15% and for women, 18%; these rates have not really improved in recent years (1). Further risk factors in addition to smoking include environmental and occupational factors. In Germany, lung cancer may be accepted as an occupational disease, which is the case especially for exposures to asbestos and radon; more rarely, polycyclic aromatic hydrocarbons, chromates, crystalline silicium dioxide, arsenic, nickel, and chloromethyl methylether (2). Viruses also play a part in the genesis of lung cancer. Large cell lymphoepithelial lung carcinoma, a rare variant of large cell carcinoma, is associated with the Epstein-Barr virus (3). Human papillomaviruses (HPV) have also been associated with the development of lung cancer. There are notable geographical differences, however. In Germany, maximum HPV detection rates of 4.2% have been reported, whereas in certain regions of Asia these were as high as 80% (4). Smoking is, however, by some margin the most common cause for the development of lung cancer (2).

Heterogeneity of large cell carcinoma of the lung: an immunophenotypic and miRNA-based analysis.

Abstract: Large cell carcinomas (LCCs) of the lung are heterogeneous and may be of different cell lineages. We analyzed 56 surgically resected lung tumors classified as LCC on the basis of pure morphologic grounds, using a panel of immunophenotypic markers (adenocarcinoma [ADC]-specific, thyroid transcription factor-1, cytokeratin 7, and napsin A; squamous cell carcinoma [SQCC]-specific, p63, cytokeratin 5, desmocollin 3, and Δnp63) and the quantitative analysis of microRNA-205 (microRNA sample score [mRSS]). Based on immunoprofiles 19 (34%) of the cases were reclassified as ADC and 14 (25%) as SQCC; 23 (41%) of the cases were unclassifiable. Of these 23 cases, 18 were classified as ADC and 5 as SQCC according to the mRSS. Our data show that an extended panel of immunohistochemical markers can reclassify around 60% of LCCs as ADC or SQCC. However, a relevant percentage of LCCs may escape convincing immunohistochemical classification, and mRSS could be used for further typing, but its clinical relevance needs further confirmation.

β-catenin is constitutively active and increases STAT3 expression/activation in anaplastic lymphoma kinase-positive anaplastic large cell lymphoma

Abstract: Background The role of β-catenin in cancer has been most studied in tumors of epithelial cell origin. The functional status and biological significance of this protein in anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma is unknown.Design and Methods ALK-positive anaplastic large cell lymphoma cell lines and patients’ tumor samples were examined for status of β-catenin expression and signaling. The subcellular localization of β-catenin was assessed using immunohistochemistry, sub-cellular fractionation and confocal microscopy, while its transcriptional activity was studied using the TOPFlash/FOPFlash luciferase reporter assay. To examine the biological significance of β-catenin, short interfering RNA was used to knock-down its expression; the resulting biological effects were studied using trypan-blue exclusion and MTS assay, and the impact on its various downstream targets was assessed using quantitative real-time polymerase chain reaction and western blots.Results β-catenin was transcriptionally active in three of three ALK-positive anaplastic large cell lymphoma cell lines, and this finding correlates with the nuclear localization of β-catenin in these cells and the neoplastic cells identified in most of the patients’ tumor samples. β-catenin is biologically significant in ALK-positive anaplastic large cell lymphoma, since down-regulation of β-catenin resulted in a significant reduction in their cell growth. Down-regulation of β-catenin led to a marked reduction in both the total protein level and the activated/phosphorylated form of STAT3, another signaling protein previously shown to be important in the pathogenesis of ALK-positive anaplastic large cell lymphoma. In contrast to some of the oncogenic tyrosine kinases, modulation of nucleophosmin-anaplastic lymphoma kinase expression did not result in any detectable change in the protein level, nuclear localization or tyrosine phosphorylation of β-catenin; however, inhibition of nucleophosmin-anaplastic lymphoma kinase expression significantly down-regulated the transcriptional activity of β-catenin.Conclusions β-catenin signaling is constitutively active in ALK-positive anaplastic large cell lymphoma and represents a previously unknown mechanism by which the high levels of STAT3 expression and activation in these tumors are sustained. Our results suggest that the interaction between oncogenic tyrosine kinases and various cell signaling proteins may be more complex than previously believed.

Diagnostic utility of PAX8 and PAX2 immunohistochemistry in the identification of metastatic Müllerian carcinoma in effusions

Abstract: Morphologic distinction of Mullerian carcinomas from non-Mullerian carcinomas in effusion specimens by cytomorphology alone can be diagnostically challenging. Therefore, immunohistochemical adjuncts can be useful in differentiating Mullerian from non-Mullerian metastases. In this study, we evaluated the expression of PAX8 and PAX2 in malignant effusions collected from patients with known Mullerian and non-Mullerian carcinomas. Sections from cell blocks prepared from 152 effusion specimens (54 and 98 cases representing metastases from Mullerian and non-Mullerian primaries, respectively) were immunostained with rabbit polyclonal antibodies against PAX8 and PAX2. Immunopositivity was defined as the presence of strong nuclear staining in at least 25% of the tumor cells. Fifty-two (96%) and 13 (24%) of the 54 Mullerian carcinomas were positive for PAX8 and PAX2, respectively. PAX8 positivity was seen in only four (4%) of 98 non-Mullerian carcinomas; these represented metastasis from a large cell neuroendocrine lung carcinoma, papillary thyroid carcinoma, renal cell carcinoma, and acinic cell carcinoma of the parotid gland. PAX2 positivity was not seen in any of the non-Mullerian carcinomas. The results demonstrate that both PAX8 and PAX2 are highly specific markers for metastatic Mullerian carcinomas in cell block preparations from effusion specimens (96% and 100%, respectively). PAX8, however, is more sensitive than PAX2 in identifying Mullerian carcinomas in fluids (96% versus 24%). Overall, immunohistochemistry for PAX8 and PAX2 represent diagnostically useful adjuncts in identifying a Mullerian carcinoma as a source of a malignant effusion. Diagn. Cytopathol. 2010. © 2010 Wiley-Liss, Inc.

CCL11–CCR3 Interactions Promote Survival of Anaplastic Large Cell Lymphoma Cells via ERK1/2 Activation

Abstract: CCR3 is a specific marker of anaplastic large cell lymphoma (ALCL) cells. ALCL cells also express CCL11, a ligand for CCR3, leading to the hypothesis that CCL11 may play an autocrine role in ALCL progression. In this study, we investigated a role of CCL11 in cell survival and growth of human Ki-JK cells, established from an ALCL patient, and murine EL-4 lymphoma cells. Both Ki-JK and EL-4 cells expressed cell surface CCR3. CCL11 increased cell survival rates of Ki-JK cells in a dose-dependent manner, whereas it promoted EL-4 cell proliferation. Furthermore, CCL11 induced phosphorylation of extracellular signal-regulated kinase (ERK) 1/2 in both Ki-JK cells and EL-4 cells. Cell survival and tumor proliferation promoted by CCL11 was completely blocked by inhibition of ERK phosphorylation. CCL11 induced expression of antiapoptotic proteins, Bcl-xL and survivin, in Ki-JK cells. CCL11 also enhanced tumor growth of EL-4 and Ki-JK cells in vivo. Consistent with these results, tumor cells of cutaneous ALCL expressed CCR3 and increased levels of phosphorylated ERK1/2, Bcl-xL, and survivin in situ. Thus, our findings prompt a novel therapeutic approach to treat relapses of an aggressive form of lymphoma based on the discovery that a cell surface marker of disease functions as a critical autocrine growth receptor.

Differential expression and function of the caveolin-1 gene in non-small cell lung carcinoma

Abstract: This study was designed to clarify the function of caveolin-1 (Cav-1) in the development of lung cancer by investigating the mutation and protein expression of the Cav-1 gene in non-small cell lung carcinoma (NSCLC). Quantum dot immunofluorescence histochemistry was used to evaluate Cav-1 protein expression and subcellular localization in the lung cancer tissue microarray including 140 cases of lung cancer and 20 cases of non-cancerous lung tissue. Mutation of the Cav-1 gene in exon 1 and exon 3 was detected by polymerase chain reaction-single strand conformation polymorphism and sequencing. The positive rates of Cav-1 expression were 49.3% (69/140) in NSCLC group, significantly lower than the 100% (20/20) rate in the control group. Adenocarcinomas (16.7%), adenosquamous carcinomas (38.4%), squamous cell carcinomas (67.1%) and large cell lung cancers (66.7%) displayed Cav-1 positive staining, suggesting a gradient of Cav-1 expression according to tumor histotype-related aggressiveness. High-expression of Cav-1 protein was statistically correlated with pathologic TNM stage and lymph node metastasis. No mutation could be detected in exon 1 and exon 3 from all Cav-1 protein negative expression of NSCLC samples. Cav-1 immunoreactivity in lung cancer is histotype-dependent, increased Cav-1 expression indicates the malignant progression and high invasion features of NSCLCs. Deregulation of Cav-1 expression in NSCLCs may not correlate with mutation.

Absence of Merkel cell polyomavirus in primary parotid high-grade neuroendocrine carcinomas regardless of cytokeratin 20 immunophenotype.

Abstract: High-grade neuroendocrine carcinoma of the salivary glands is a rare malignancy that can be difficult to distinguish from metastatic neuroendocrine (Merkel cell) carcinoma of the skin, which often occurs on the head and neck and may metastasize to lymph nodes in or adjacent to salivary glands, particularly the parotid gland. As the 2 tumors have morphologic and immunophenotypic overlap, additional diagnostic tools may be clinically useful. Merkel cell carcinoma is known to harbor Merkel cell polyomavirus in up to 80% of cases. However, the presence or absence of this virus in salivary gland neuroendocrine carcinomas has not been investigated. We evaluated 7 primary salivary gland high-grade neuroendocrine carcinomas (all from the parotid) for the virus by both immunohistochemistry (CM2B4 clone) and real-time polymerase chain reaction directed against the conserved small T antigen. Five of the tumors had small cell morphology, and 2 had large cell morphology. All were either chromogranin and/or synaptophysin positive. Four of the 5 small cell (80%) and 1 of the 2 large cell (50%) carcinomas were cytokeratin 20 positive. All but 1 case had cervical lymph node metastases at presentation. Merkel cell polyomavirus T antigen was not detected in any of the 7 tumors, either by immunohistochemistry or by polymerase chain reaction with adequate controls. These observations suggest that primary parotid high-grade neuroendocrine carcinoma arises from a biological pathway that is different from that of cutaneous Merkel cell carcinomas. Furthermore, viral testing may aid in distinguishing the 2 tumor types, as a positive result would favor a metastasis.

Preferential expression of potential markers for cancer stem cells in large cell neuroendocrine carcinoma of the lung. An FFPE proteomic study

Abstract: Background Large cell neuroendocrine carcinoma (LCNEC) of the lung, a subtype of large cell carcinoma (LCC), is characterized by neuroendocrine differentiation that small cell lung carcinoma (SCLC) shares. Pre-therapeutic histological distinction between LCNEC and SCLC has so far been problematic, leading to adverse clinical outcome. We started a project establishing protein targets characteristic of LCNEC with a proteomic method using formalin fixed paraffin-embedded (FFPE) tissues, which will help make diagnosis convincing.

Large cell neuroendocrine carcinoma of the endometrium: an extremely uncommon diagnosis, but worth the efforts.

Abstract: Neuroendocrine carcinomas (NEC) of the female genital tract are aggressive and uncommon tumors. They usually involve the cervix and ovary, and are seen very rarely in the endometrium. The overwhelming majority of endometrial NECs are of conventional small cell type (up to 60 cases). Only seven cases of large cell type NEC of the endometrium have been reported. We report a case of large-cell neuroendocrine carcinoma (LCNEC) of the endometrium in a 70-year-old female. The case is described for its rarity and shows that a high index of suspicion can help the pathologist to use immunohistochemistry and in turn help in selection of appropriate chemotherapy.

BCL6 gene rearrangement and protein expression are associated with large cell presentation of extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue

Abstract: Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) is an indolent B-cell lymphoma, which is often localized in the stomach. It is characterized by typical morphology, immunology, cytogenetics and expression profile. The coexistence of a large B-cell lymphoma and a MALT lymphoma in the gastrointestinal tract is defined as a composite lymphoma (ComL) and, as we have previously shown, is almost always the consequence of secondary transformation of MALT lymphoma. Here, we have analyzed a panel of seven MALT lymphomas, seven ComL and thirteen large cell variants of marginal zone B-cell lymphomas (MZBL) using FISH for the detection of rearrangements of IGH, MALT1, BCL6, BCL10 and FOXP1 and immunohistochemistry for Bcl6, Bcl10 and FoxP1. Translocations involving IGH were found in 10/27 lymphomas including two cases with IGH-BCL6 fusion and one with IGH-BCL10 fusion; in 7/10 cases, the translocation partner was not identified. Bcl10 and FoxP1 protein expression was heterogeneous throughout the series. Genetic rearrangements of BCL6 and Bcl6 protein expression were found almost exclusively in the large cell components of the ComL and the large cell extranodal MZBL (p = 0.2093 and p = 0.0261, respectively). These findings suggest Bcl6 as a marker for transformation of MALT lymphoma.

C-MYC rearrangement may induce an aggressive phenotype in anaplastic lymphoma kinase positive anaplastic large cell lymphoma: Identification of a novel fusion gene ALO17/C-MYC

Abstract: Anaplastic lymphoma kinase (ALK) positive anaplastic large cell lymphoma (ALCL) is usually associated with a favorable prognosis. We describe an 11-year-old girl patient with ALK positive ALCL bearing t(2;5)(p23;q35) and t(8;17)(q24;q25) translocations who had an aggressive clinical course despite various combinations of intensive chemotherapy. Southern blot analysis identified C-MYC rearrangement. Immunohistochemistry and Northern and Western blot analyses revealed cmyc overexpression. A new fusion between ALO17 (ALK lymphoma oligomerization partner on chromosome 17) and C-MYC was identified by the 50-rapid amplification of cDNA ends. This new fusion may have possibly provoked the poor prognosis in this patient with ALK positive ALCL, and C-MYC rearrangement may indicate poor prognosis in ALCL.

Unusual form of superficial spreading squamous cell carcinoma of cervix involving the endometrium, bilateral tubes and ovaries: a case report with literature review

Abstract: Although the majority of metastatic ovarian tumors arise within the female genital tract, squamous cell carcinoma of the cervix is a rare form of metastases to the bilateral ovaries by endometrial and transtubal spreading. A 53-year-old woman was referred to the oncology clinic with postmenopausal bleeding. On vaginal examination, a 3 cm tumor arising from the cervix was inspected. Multiple cervical biopsies and endocervical curettage revealed large cell, non-keratinized squamous cell cervix carcinoma. Radical hysterectomy and bilateral salpingo-oophorectomy were performed. Bilateral pelvic and para-aortic lymph nodes were also removed. The final pathology report revealed endometrial, focal myometrial, bilateral tubal mucosal, fimbrial and bilateral ovarian squamous cell carcinoma involvement. Pelvic and para-aortic nodes were free from metastases. Although the incidence of ovarian metastases of adenocarcinoma of the cervix is significantly higher, squamous cell carcinoma may also metastasize to the ovaries by endometrial and transtubal spreading in the absence of lymph node involvement. Especially in young patients for whom preservation of the ovaries is supposed, gross intraoperative inspection of the radical hysterectomy specimen and endometrium should be done and ovaries should be evaluated carefully.

Cytological, histological, and immunohistochemical findings of pulmonary carcinomas with basaloid features.

Abstract: Pulmonary basaloid carcinoma (BC), a variant of large cell, nonsmall cell carcinoma (NSCC), and basaloid squamous cell carcinoma (BSQCC) can show features similar to small cell carcinoma (SCC) and large cell neuroendocrine carcinoma (LCNEC). Distinction from SCC, especially on FNA, is therapeutically relevant. We describe cytological, histological, and immunohistochemical features of BC and BSQCC. Numerous cytologic features were documented in cytologic preparations. Similar features and architecture were evaluated in the resections. Immunohistochemical results were recorded. Histologically confirmed BC (n = 3) and BSQCC (n = 3) were included. Five FNAs of SCC, (four with histologic follow-up) were studied for comparison of cytological, histological, and immunohistochemical findings. In cytologic preparations of BC/BSQCC, cells were arranged mostly as tightly cohesive clusters (n = 4) or singly and in clusters (n = 2) with a predominance of clusters. Cytologic features of BC and BSQCC were similar: palisading (n = 6), crush artifact (n = 6), hyperchromasia (n = 5), focal nuclear molding (n = 6; very rare in 2/6), nucleoli, usually pinpoint (n = 3), scant cytoplasm (n = 6), necrosis (n = 5), apoptosis (n = 4), squamous differentiation (n = 1). BSQCC tended to have occasional larger cells, including keratinizing cells in one case. Histologic sections (n = 6) showed neuroendocrine features, including organoid arrangements, nests, and palisading. BC and BSQCC show overlapping features with SCC and LCNEC in cytological and histological specimens. Unlike SCCs, BC/BSQCC lack prominent nuclear molding, show tightly cohesive cell clusters, and demonstrate palisading. However, immunostains were the very helpful and probably necessary to accurately diagnosing BC/BSQCC, which show the immunostaining pattern of p63 (+), HMWCK (+), and TTF-1 (-).

Clinical utility of chromogranin A and octreotide in large cell neuro endocrine carcinoma of the uterine corpus

Abstract: Primary neuroendocrine tumors of the female genital tract have been described in the cervix, ovaries and uterus. Large cell neuroendocrine carcinoma (LCNC) of the uterine corpus is the least common and appears to behave the most aggressively. We report a rare case of a large cell neuroendocrine tumor of the endometrium. These tumors are not well characterized, unlike neuroendocrine tumors of the uterine cervix. Consequently, the optimal management remains still unclear. The treatment of our case consisted of surgery, radiotherapy, chemotherapy, and octreotide. Despite the aggressive treatment, the patient died of disease progression 12 months after the initial diagnosis. We discuss the diagnosis, prognosis, and treatment options for LCNC of the genital tract, and potential future therapeutics.