Small Cell Component Research Articles

Embryonal tumor with abundant neuropil and true rosettes: a report of three cases of a rare tumor, with an unusual case showing rhabdomyoblastic and melanocytic differentiation

Embryonal tumor with abundant neuropil and true rosettes (ETANTR) is an increasingly recognized entity that belongs to the family of embryonal tumors of the CNS. The authors present three cases of this rare tumor that were encountered at King Hussein Cancer Center, Amman, Jordan. Discussion of the clinicopathological findings is presented along with a recent literature review. Sixteen-, 57- and 30-month-old children presented with tumors located in the pineal gland, the right fronto- parieto-temporal region and the cerebellum, respectively. The findings of hypocellular neuropil as well as the characteristic ependymoblastic rosettes were seen. In addition the third case showed an abnormal combination of patterns including melanocytic and rhabdomyoblastic differentiation. The tumors stained positively for synaptophysin in the neuropil and small cell component, while the ependymoblastic rosettes stained for vimentin only. Epithelial membrane antigen and CD99 were negative in all components. One of the cases showed tetraploidy of chromosome 2. All cases exhibited an aggressive course. This is a rare and recently recognized tumor with dismal outcome, and reporting of additional new cases should help in gaining more knowledge about it.

CD133 expression is associated with small round blue cell tumour morphology in human central nervous system neoplasms

CD133 is considered to be a marker for brain tumour-initiating cells. However, most data on CD133 are derived from animal or in-vitro studies. The aim of this study was to characterize CD133 expression, and the distribution and morphological features of CD133(+) cells, in primary and secondary human central nervous system (CNS) neoplasms. Tumours were analysed by real-time reverse transcription polymerase chain reaction, western blot, flow cytometry and immunohistochemistry. Our results show that only small round blue cell tumours (SRBCTs) exhibit strong and consistent CD133 expression. Interestingly, glioblastomas, large-cell carcinomas and sarcomas were negative for CD133. Only glioblastomas with a focal small-cell component exhibited CD133 immunoreactivity in the SRBCT component. In addition, CD133 expression did not correlate with the expression of other markers associated with stem cell differentiation, including CD15 and nestin. CD133 expression in human CNS neoplasms is independent of the grade of malignancy but strongly correlates with SRBCT morphology. Together with recent findings showing that CD133 is quickly upregulated upon hypoxia and that CD133(-) cells can also exhibit stem cell properties, our data strongly question the suitability of CD133 as a brain tumour stem cell marker in vivo.

Complete remission in a patient with metastatic mixed adenocarcinoma/extrapulmonary small cell carcinoma of the prostate

Approximately 10% of all extra-pulmonary small cell carcinoma (EPSCC) arises in the prostate either as de novo mixed adenocarcinoma with small cell components or a pure small cell carcinoma. Extensive disease carries a median survival of about 10 months in retrospective studies. We present a case managed aggressively with concomitant hormonal and chemotherapy, now 36 months without evidence of disease. At a routine physical, a 55 year male was found to have a 5 cm left upper lobe lung mass, invading his 3rd rib. An FNA revealed an adenocarcinoma of unknown primary. His PSA was elevated to 8 ng/mL and a prostate biopsy revealed Gleason 9 adenocarcinoma with neuro-endocrine/SCC components. A bone scan revealed extensive bone metastasis. He was managed aggressively with concomitant cisplatin, etoposide and hormonal therapy and received 73 Gy of radiation to the prostate. PET scans demonstrated marked response to chemotherapy. PSA and chromogrannin levels down trended to normal limits. His most recent PET scan in July 2010 revealed no evidence of disease and is in remission. We present a unique case of metastatic mixed adenocarcinoma/SCC of the prostate, in which the patient survived more than 36 months with complete remission after initiation of aggressive hormonal and chemotherapy. Data on survival in this patient population is limited to case reports, and ordinarily carries a poor prognosis of less than 1 year. In patients with clinical and pathologic features of mixed disease, initiation of early multi-modal therapy is warranted. Additionally, it may be of prognostic significance to biopsy any metastatic lesion.

Pediatric primary intramedullary spinal cord glioblastoma

Spinal cord tumors in pediatric patients are rare, representing less than 1% of all central nervous system tumors. Two cases of pediatric primary intramedullary spinal cord glioblastoma at ages 14 and 8 years are reported. Both patients presented with rapid onset paraparesis and quadraparesis. Magnetic resonance imaging in both showed heterogeneously enhancing solitary mass lesions localized to lower cervical and upper thoracic spinal cord parenchyma. Histopathologic diagnosis was glioblastoma. Case #1 had a small cell component (primitive neuroectodermal tumor-like areas), higher Ki67, and p53 labeling indices, and a relatively stable karyotype with only minimal single copy losses involving regions: Chr8;pter-30480019, Chr16;pter-29754532, Chr16;56160245–88668979, and Chr19;32848902-qter on retrospective comparative genomic hybridization using formalin-fixed, paraffin-embedded samples. Case #2 had relatively bland histomorphology and negligible p53 immunoreactivity. Both underwent multimodal therapy including gross total resection, postoperative radiation and chemotherapy. However, there was no significant improvement in neurological deficits, and overall survival in both cases was 14 months.This report highlights the broad histological spectrum and poor overall survival despite multi modality therapy. The finding of relatively unique genotypic abnormalities resembling pediatric embryonal tumors in one case may highlight the value of genome-wide profiling in development of effective therapy. The differences in management with intracranial and low-grade spinal cord gliomas and current management issues are discussed.

Distinct molecular signatures in pediatric infratentorial glioblastomas defined by aCGH

Glioblastomas (GBM) are rare in children, but reportedly have more varied outcome which suggests differences in tumor etiology compared to typical GBM of adults. To investigate this we performed high resolution array comparative genomic hybridization (aCGH) analysis on three pediatric infratentorial GBM, ages 3.5, 7 and 14 years. Two of these tumors occurred in the brainstem and one in the spinal cord. While histologically typical, one brainstem tumor showed mainly pleomorphic astrocytic cells, whereas the other brainstem and spinal tumors showed a GFAP positive small cell component. Whole chromosomal gains (#1 and #2) and loss (#20) were seen only in the pleomorphic brainstem GBM, which also showed a high level of segmental genomic copy number changes. Segmental loss involving chromosome 8 was seen in all three tumors (Chr8;133039446-136869494, Chr8;pter-3581577, and Chr8;pter-30480019 respectively), whereas loss involving chromosome 16 was seen in only 2 cases with small cell components (Chr16;31827239-qter and Chr16;pter-29754532). Segmental gain of chromosome 7 was shared only between the 2 brainstem cases (Chr7;17187166-qter and Chr7;69824947-qter). Chromosome 17 showed segmental gain of 17q in the backdrop of loss of 17p only in case 1. Segmental gain of chromosome 1q was seen only in case 2. The spinal GBM showed a relatively stable karyotype with a unique loss of Chr19;32848902-qter. None of the frequent losses, gains and amplifications known to occur in adult GBM were identified, suggesting that pediatric infratentorial glioblastomas show a molecular karyotype that was more characteristic of pediatric embryonal tumors than adult GBM.

Diagnosis and staging in gastrointestinal lymphoma

The diagnosis gastrointestinal lymphoma can be made on endoscopic biopsies in the vast majority of cases. Definitive subtyping of the lymphoma according to the WHO classification with the use of additional immunological and molecular markers is the cornerstone for further decision making. Several lymphomas may occur multifocally or show both small cell and large cell components. Therefore, a second endoscopy with an extensive biopsy protocol (mapping) may be mandatory. Staging procedures are required for therapeutic decision making and should include CT-scan, laboratory studies and bone marrow examination as required in other lymphomas. Additional studies must be performed depending subtype and localisation of the lymphoma. In gastric lymphoma endosonography reveals prognostic information. In marginal zone lymphoma of MALT-type attention to other MALT-sites and autoimmune diseases is necessary. In enteropathy-associated T-cell lymphoma screening for coeliac disease and enteroscopy are required. In several lymphomas (diffuse large B-cell lymphoma and mantle cell lymphoma) a PET-scan is considered as standard of care. The value of staging procedures after treatment is less well defined. At least in gastric lymphomas, histology is the gold standard after treatment and during follow-up.

Obligate basal cell component in salivary oncocytoma facilitates distinction from acinic cell carcinoma

The differential diagnosis between benign salivary oncocytoma (ONC) and low-grade malignant acinic cell carcinoma (ACC) can be difficult due to a significant histomorphological overlap of the structural and cytological presentation of both tumor types. To the best of our knowledge a comprehensive study comparing (immuno-)histological markers in cases of difficult differential diagnosis between ONC and ACC has not yet been performed. We investigated a panel of different immunohistochemical (CK5/6, CK14, CK7, CK18, p63 and Ki67) and histochemical (PAS, α-amylase) markers in 12 cases of ONC and 19 cases of ACC. The statistically significant stronger expression of CK7 in ONC and stronger expression of PAS and α-amylase in ACC in routine practice each is hampered by a pronounced overlap between both tumor groups. The obligate presence of an additional small basal cell component in all cases of ONC, demonstrable with p63 and CK5/6, enables a straightforward distinction from ACC, being constantly devoid of a basal cell component. Unexpectedly, CK14 is not a suitable marker for a reliable proof of these basal cells. The detection of this basal cell component in ONC in routine Hematoxylin–eosin stain is difficult and in some cases not possible; therefore, immunohistochemistry with p63 or CK5/6 is recommended for selected cases.

Involvement of mTOR and survivin inhibition in tamoxifen-induced apoptosis in human hepatoblastoma cell line HepG2

Hepatoblastoma is characterized by a diversity of differentiation patterns, some resembling stages of liver development, and occasionally associated with clinical behavior. Our hypothesis is that histologic microheterogeneity in hepatoblastoma correlates with molecular heterogeneity and reflects different stages of developmental arrest. We studied the activation status of the Wnt and Notch pathways and the differential expression of hepatocyte nuclear factor 4α, EGFR, and IGF2 genes, relevant to liver development and malignant transformation in histologic variants of hepatoblastoma. Eighty-seven percent of 32 hepatoblastoma cases studied carried CTNNB1 mutations within the ubiquitination domain. Large deletions were seen only in pure fetal cases, also characterized by CCND1 and GLUL (GS) overexpression. Hepatoblastomas with small-cell type appeared clearly distinct and were the only ones with negative GLUL expression. HES1 expression and HES1/AXIN2 used to measure Notch versus Wnt activation ratio were particularly elevated in pure fetal cases and were lowest in hepatoblastomas with small-cell component. Hepatocyte nuclear factor 4α was relatively elevated only in embryonal hepatoblastomas. DLK1, DKK, AXIN2, IGF2, and EGFR were increased in all subtypes. Our results support the hypothesis that hepatoblastoma microheterogeneity correlates with molecular heterogeneity. DLK1, a marker of bipotential oval cells, is consistently up-regulated in hepatoblastoma. Therefore, we speculate that hepatoblastomas may arise from a proliferating bipotential precursor. Wnt activation is prevalent in hepatoblastomas, most significantly in predominantly embryonal and mixed types, whereas Notch activation, needed for cholangiocytic differentiation at a more differentiated state, is highest in pure fetal hepatoblastomas. The relative Wnt versus Notch activation appears useful in stratifying different subtypes.

Characterization of a new small cell lung cancer (SCLC) cell line STP54 derived from a metastatic bioptate of a combined type of SCLC with Non-SCLC component.

Small cell lung cancer constitutes 15-20% cases of lung cancers, currently the leading cause of death from malignant diseases. It also causes the demise of >90% of affected individuals in 5 years. We have established a new SCLC cell line STP54 derived from fine needle aspirate of metastatic supraclavicular lymph node of 54 -year-old women for model experiments. The primary tumor was diagnosed by histopathological examination as combined type of small cell lung cancer with a non-small cell component. We cultured the cancer cells in the RPMI 1640 medium. In the long-term culture only the small cell component survived. The cell line was established after 30 passages and then characterized by performing cell morphology, cell growth analysis, tumorigenicity in vitro and flow cytometry analysis of selected markers (like NCAM, cytokeratines, HLA-ABC, Fas, Bcl-2, p53, CXCR4, CD210). The cells were growing in floating aggregates and show features suggesting its invasiveness. We suggest that this new cell line may serve as a valuable tool for further studies on lung tumor biology, molecular pathogenesis and metastatic mechanism.

Gene expression profiling reveals signatures characterizing histologic subtypes of hepatoblastoma and global deregulation in cell growth and survival pathways

Hepatoblastoma is the most common malignant tumor of the liver of children worldwide. Histologically, hepatoblastomas show marked variation in the type and proportion of epithelial (fetal, embryonal, or small cell) and mesenchymal components with differing prognosis and response to therapy. The pure fetal-type hepatoblastoma, presenting as stage 1 and resectable, has the best prognosis, whereas the small cell histology has been associated with unfavorable outcome. Using gene expression profiling, we demonstrate that in addition to Wnt pathway deregulation, cell growth and survival pathways are also globally deregulated in hepatoblastomas. Furthermore, the different histologic subtypes are characterized by specific gene expression and pathway signatures that give insight into the degree of molecular heterogeneity that is present among these tumors. Although Wnt signaling pathway upregulation is common to all histologic types of hepatoblastoma, this pathway is even more significantly deregulated in aggressive hepatoblastomas. In addition, deregulation of MAPK signaling pathway and antiapoptotic signaling is preferentially upregulated in aggressive epithelial hepatoblastomas with a small cell component. The gene expression signatures reported here provide possible prognostic and diagnostic markers as well as therapeutic targets for this disease.

Histologic subtypes of hepatoblastoma are characterized by differential canonical Wnt and Notch pathway activation in DLK+ precursors

Hepatoblastoma is characterized by a diversity of differentiation patterns, some resembling stages of liver development, and occasionally associated with clinical behavior. Our hypothesis is that histologic microheterogeneity in hepatoblastoma correlates with molecular heterogeneity and reflects different stages of developmental arrest. We studied the activation status of the Wnt and Notch pathways and the differential expression of hepatocyte nuclear factor 4alpha, EGFR, and IGF2 genes, relevant to liver development and malignant transformation in histologic variants of hepatoblastoma. Eighty-seven percent of 32 hepatoblastoma cases studied carried CTNNB1 mutations within the ubiquitination domain. Large deletions were seen only in pure fetal cases, also characterized by CCND1 and GLUL (GS) overexpression. Hepatoblastomas with small-cell type appeared clearly distinct and were the only ones with negative GLUL expression. HES1 expression and HES1/AXIN2 used to measure Notch versus Wnt activation ratio were particularly elevated in pure fetal cases and were lowest in hepatoblastomas with small-cell component. Hepatocyte nuclear factor 4alpha was relatively elevated only in embryonal hepatoblastomas. DLK1, DKK, AXIN2, IGF2, and EGFR were increased in all subtypes. Our results support the hypothesis that hepatoblastoma microheterogeneity correlates with molecular heterogeneity. DLK1, a marker of bipotential oval cells, is consistently up-regulated in hepatoblastoma. Therefore, we speculate that hepatoblastomas may arise from a proliferating bipotential precursor. Wnt activation is prevalent in hepatoblastomas, most significantly in predominantly embryonal and mixed types, whereas Notch activation, needed for cholangiocytic differentiation at a more differentiated state, is highest in pure fetal hepatoblastomas. The relative Wnt versus Notch activation appears useful in stratifying different subtypes.

The Expression of TTF-1 in Small Cell Carcinoma of Urinary Bladder

Small cell carcinoma (SMCC) of the urinary bladder is a rare tumor, accounting for less than 1% of all malignant neoplasms in the urinary bladder. Recently, thyroid transcription factor-1 (TTF-1), a putative marker for tumors originating from the lung and thyroid, was found to be expressed in SMCC of the urinary bladder, albeit in only a very small number of cases. Herein we report two additional cases of SMCC of the urinary bladder expressing TTF-1. The first patient was a 68-year-old white male with a 5-year history of a small focus of prostatic adenocarcinoma (biopsy proven) who was being treated with brachytherapy. He subsequently developed multiple large nodules at the base of the bladder, which by biopsy identified the presence of loosely cohesive small cells with minimal cytoplasm, coarsely and finely granular chromatin and indistinct nucleoli. Tumor cells were positive for TTF-1, CD56, chromogranin, synaptophysin and Cam 5.2, and negative for PSA. The location, morphological and immunochemical features of the tumor were diagnostic for SMCC of the urinary bladder. The second patient was a 76-year-old white female with a history of recurrent episodes of urinary tract infections. A biopsy showed a poorly differentiated carcinoma. The subsequent cystectomy revealed the presence of a 4.5 x 4.5 x 2.1 cm. tumor composed of a mixture of infiltrating high grade urothelial carcinoma and small cell carcinoma. The small cell component possessed similar morphological and immunohistochemical features as previously described in the first case, including positive expression for TTF-1. These two cases illustrate and concur with previous assertions that TTF-1 cannot be used to distinguish primary SMCC of the urinary bladder from metastatic SMCC of lung. [N A J Med Sci. 2009;2(3):94-96.]

Mucin‐producing gallbladder adenocarcinoma with focal small cell and large cell neuroendocrine differentiation associated with pancreaticobiliary maljunction

Herein is reported a case of mucin-producing carcinoma of the gallbladder in a 55-year-old Japanese woman. Although the patient's status and laboratory data initially suggested biliary pancreatitis due to gallstone, radiography and endoscopy confirmed the presence of pancreaticobiliary maljunction and a gallbladder tumor with excessive mucin, in which the duodenal papilla and the common bile duct were impacted. Following surgery, the gallbladder tumor was histopathologically diagnosed as a mixed endocrine-exocrine carcinoma. The carcinoma predominantly consisted of papillary, but also contained some tubular adenocarcinomatous components. Additionally, small foci of small cell and large cell neuroendocrine carcinomatous components were observed. There was no evidence of lymph node metastasis, distant metastasis, or direct invasion outside the gallbladder. Thus, the final classification of pT2N0M0 stage II was given to this lesion, according to the Union Internationale Contre le Cancer guidelines. The postoperative course was uneventful, and the carcinoma had not recurred in the absence of chemoradiotherapy for a period of 20 months. Mucin-producing gallbladder carcinoma is a rare clinical condition that can occur in patients with pancreaticobiliary maljunction. Detailed investigation of this condition is important to develop and refine effective therapeutic strategies.

A case of uterine cervical adenocarcinoma associated with small cell carcinoma

Extrapulmonary small cell carcinomas are often associated with carcinomas of other cell types. Although a hypothesis that extrapulmonary small cell carcinomas arise from a multipotential stem cell could explain this mixed feature, recent molecular evidence supports another possibility that the small cell component may arise as a late-stage phenomenon in the progression of more organ-typical carcinomas. Here, we report a case of uterine cervical adenocarcinoma containing 30% of small cell carcinoma. Adenocarcinoma was located in the endometrial side of the tumor that was adjacent to the normal cervical region, while small cell carcinoma was located in the periphery of the tumor. The transition from adenocarcinoma to small cell carcinoma was observed in the boundary area. These findings suggest that cervical small cell carcinoma can be differentiated from pre-existing adenocarcinoma and offer further support to the hypothesis that the small cell component arises as a late-stage phenomenon in the progression of more organ-typical carcinomas.

PIK3CA, BCL-6, MLL and FOXP1 in the transformation and prognosis of MALT lymphoma

8577 Background: Recent study showed that the most common gene abnomalities in gastrointestinal MALT lymphoma included 3q26.2 -27,11q23–24 amplifications and t(3;14) (p14.1;q32). MALT lymphoma shared the same aberrations with DLBCL but with a lower rate, suggesting a clonal transformation from low to high-grade lymphoma. Four important oncogenes were found to be involved in these aberrations, including PIK3CA, BCL-6, MLL and FOXP1. Rare studies about the role of expression of 4 oncogenes in the transformation and prognosis of MALT lymphoma were seen. Methods: We conducted this research to explore the expression of PIK3CA, BCL-6, MLL and FOXP1 in 40 gastrointestinal MALT lymphoma cases that were classified to large-cell (involving 5%-20% large cells in the specimen) or non- large cell (involving <5% large cells) pathologic subtype and 10 transformed gastrointestinal DLBCL specimens (involving >20% large cells with residual small-cell components) through immunohistochemistry staining. Prognostic significance of 4 indexes was also analyzed. Results: In 40 gastrointestinal MALT lymphoma cases, large-cell subtype were found in 7 (17.5%). The percentage of positive expression of PIK3CA, BCL-6, MLL and FOXP1 in non-large cell subtype was 42.4%, 15.2%, 66.7% and 12.0%, while in large-cell subtype the percentage was 42.9%, 28.6%, 100% and 28.0%, respectively. Among non-large cell subtype, large-cell subtype of MALT lymphoma and transformed DLBCL, only the rate of FOXP1 expression (>75% positive staining cells) was raised up in order (12.0%, 28.0% and 40%, P=0.046). PIK3CA expression (18/40) was an independent negative prognostic variable on the PFS (P=0.008) .The positive expression of BCL-6, MLL and FOXP1 did not show any significant prognostic value. Conclusions: Our data suggests that PIK3CA, a novel molecular index, can predict a worse prognosis in gastrointestinal MALT lymphoma. The study also provides some clues to further genetic research that will finally demonstrate the role of FOXP1 in the transformation from MALT lymphoma to DLBCL. No significant financial relationships to disclose.

Composite carcinoma of the colon: A case report with literature review

Mixed composition carcinomas of the large intestine are rare. The aggressiveness of these malignant tumors depends on the components of the tumor. We present the case of a middle-aged man who developed an acute surgical abdomen due to perforation of a mixed composition carcinoma with a dominant small cell component. To the best of our knowledge this is the first case report of a composite cecal carcinoma with lymph node metastases from both the small cell and adenocarcinoma components.

Pattern of Relapse in Localized Gastric Lymphoma Registered within the Prospective German Multicenter Study GIT NHL 01/92.

Introduction: In 2001 (Koch et al.,JCO) we published the treatment results of 185 patients (pts) with localized primary gastric lymphoma (PGL) registered within the GIT NHL 01/92 German multicenter study. After a median time of observation of 130 months we present clinical and pathological features of relapsed patients.Methods: We compared treatment results in PGL after combined surgery and conservative (S/CM) versus conservative management (CM). Radiotherapy (Rx) and chemotherapy were stratified according to histological grading, stage, and the inclusion or omission of surgery as follows: PGL pts with indolent lymphomas in stage I received an extended field (EF) Rx with total abdominal irradiation and in stage II additionally a T-field preceded by 6 cycles of COP. The dose was 30 Gy for EF followed by a boost of 10 Gy on sites of tumor. All pts with aggressive PGL were treated with four (stage I) or six (stage II) cycles of CHOP-14 followed by EF Rx (stage I) or involved field Rx (stage II), dosage of Rx corresponded to Rx for indolent NHL.Results: Between the years 1992 and 1996, a total of 185 pts were registered. Recurrence of NHL occurred in 17 cases during follow-up. Analysis revealed no specific features of relapsed pts with respect to initial symptoms, clinical features (except stage II2 - more than regional lymph nodes involved) and initial treatment. DLBCL was the most common histological subtype seen in relapsed pts (58.8%). Indolent lymphoma relapsed in 41.2% pts. Interestingly 70% of the DLBCL initially had an additional small-cell component, and 56% relapsed as marginal zone B-cell lymphoma, particularly at primary site independent of the initial treatment.Conclusion: In this non-randomized study there was no disadvantage for a stomach preserving approach in the context of tumor recurrence. Patients with distant nodal involvement (Stage II2) and DLBCL relapsed more often than pts. with localized stages (Stage I/II1) and indolent lymphomas. Interestingly, aggressive lymphomas, with an initial small-cell component, predominantly relapsed as marginal zone B-cell lymphomas at primary site, while indolent lymphomas relapsed also generalized.

Primitive Small Cell Tumor With Epithelial, Gangliocytic, Neuroendocrine, and Mesenchymal Differentiation: Report of 2 Cases

The authors describe 2 tumors that, to the best of their knowledge, are hitherto undescribed. The predominant cell type was small round to fusiform dark blue cells. The dark blue cells formed distinct epithelial cords with gland-like formations with mucicarmine-positive mucus. Another distinctive component of the tumors was a mesenchymal one. The mesenchymal areas appeared benign and could be likened to a fibroma having a densely collagenous stroma, or they had spindle cells set in the myxoid background, rendering a myxoma-like appearance. Another distinctive feature was ganglion cell differentiation. Mitotic figures, including atypical forms, were found only in the small cell component. All cells were immunohistochemically negative for actin, calponin, desmin, HMB45, neurofilament protein, CD99/MIC2, Melan A, tyrosinase, serotonin, CD56, Melan A, GFAP, and S-100 protein. Cytokeratin, synaptophysin, FLI1 protein, and chromogranin antibodies reacted only in the primitive small round cells, while all the other components were cytokeratin negative. Fluorescence in situ hybridization showed that the tumors are without the EWSR1 gene translocation and gain 12p. Ultrastructurally, the cells were endowed with well-formed intercellular desmosomes membrane-bound secretory in the cytoplasm. Granules were found in the cytoplasm. We suggest the name "primitive small cell tumor with epithelial, gangliocytic, neuroendocrine, and mesenchymal differentiation" for this neoplasm.

FOXG1 is overexpressed in hepatoblastoma

Bacterial artificial chromosome array comparative genomic hybridization analysis of hepatoblastomas reveals a deletion in the 14q12 locus in 12 of 16 cases. A high frequency of copy gain is seen on chromosomes 1q, 2, 5p, 8, and 20. Frequent deletions are also seen at 6q, 17q, and 1p with less frequent gains on 4p, 6p, and 19p. 14q12 deletion locus analyses using quantitative real-time polymerase chain reaction reveals copy number gain/amplification in the region immediately telomeric to the deleted locus, including copy number gain (2- to 4-fold) of FOXG1 in 13 out of 16 tumors. This is associated with up-regulation (approximately 87-fold) of FOXG1 gene transcripts and increased protein expression. Immunostaining reveals an inverse relationship between FOXG1 expression and p21cip1 expression in all histologic subtypes. However, FOXG1 transcript levels were significantly higher (approximately 75-fold) in tumors with embryonal and small cell components when compared with pure fetal hepatoblastomas. FOXG1 has been implicated in the repression of transforming growth factor beta-induced expression of p21cip1 and cytostasis. Our findings are consistent with such a role for FOXG1. We propose that FOXG1 overexpression may contribute to the maintenance of the undifferentiated state in hepatoblastomas and could be a potential target for molecular therapeutics. This is the first report of a possible role for FOXG1 in hepatoblastoma and pediatric neoplasia.

Transcriptional profiling suggests that secondary and primary large B‐cell lymphomas of the gastrointestinal (GI) tract are blastic variants of GI marginal zone lymphoma

The pathogenetic relationship of marginal zone B-cell lymphoma (MALT lymphoma) of the gastrointestinal (GI) tract and eventually co-existing aggressive B-cell lymphoma and primary aggressive B-cell lymphoma remains to be elucidated. The RNA of laser-microdissected cells was isolated and amplified from small and/or large cell compartments of eight MALT lymphomas (small cell lymphoma, SCL), 14 GI diffuse large B-cell lymphomas (large cell lymphoma, LCL), and ten GI B-cell lymphomas with composite small and large cell compartments (ComL) and expression analyses were performed using cDNA arrays. Hierarchical cluster analysis clearly separated SCL and LCL and the small and large cell compartments of ComL. Likewise, cluster analysis with all samples of SCL, LCL, and ComL yielded two main 'small cell' and 'large cell' branches. Furthermore, 60 genes were differentially expressed between SCL and LCL, and 82 genes between the small and large cell components of ComL; 26 genes were discriminators in both settings. Use of the profiles of ComL as training sets for class prediction resulted in 95% accuracy for the classification of SCL and LCL. Collectively, the data strongly suggest that both secondary and primary aggressive B-cell lymphomas of the GI tract are blastic marginal zone lymphomas.