Breast implant-associated anaplastic large cell lymphoma: two distinct clinicopathological variants with different outcomes.

BACKGROUND: ALK-negative anaplastic large cell lymphoma associated with breast implant (i-ALCL) has been recently recognized as a distinct entity. Among 43 830 lymphomas registered in the French Lymphopath network since 2010, 300 breast lymphomas comprising 25 peripheral T-cell lymphomas (PTCL) were reviewed. Among PTCL, ALK-negative ALCL was the most frequent and all of them were associated with breast implants. PATIENTS AND METHODS: Since 2010, all i-ALCL cases were collected from different institutions through Lymphopath. Immuno-morphologic features, molecular data and clinical outcome of 19 i-ALCLs have been retrospectively analyzed. RESULTS: The median age of the patients was 61 years and the median length between breast implant and i-ALCL was 9 years. Most implants were silicone-filled and textured. Implant removal was performed in 17 out of 19 patients with additional treatment based on mostly CHOP or CHOP-like chemotherapy regimens (n = 10/19) or irradiation (n = 1/19). CHOP alone or ABVD following radiation without implant removal have been given in two patients. The two clinical presentations, i.e. effusion and less frequently tumor mass correlated with distinct histopathologic features: in situ i-ALCL (anaplastic cell proliferation confined to the fibrous capsule) and infiltrative i-ALCL (pleomorphic cells massively infiltrating adjacent tissue with eosinophils and sometimes Reed-Sternberg-like cells mimicking Hodgkin lymphoma). Malignant cells were CD30-positive, showed a variable staining for EMA and were ALK negative. Most cases had a cytotoxic T-cell immunophenotype with variable T-cell antigen loss and pSTAT3 nuclear expression. T-cell receptor genes were clonally rearranged in 13 out of 13 tested cases. After 18 months of median follow-up, the 2-year overall survival for in situ and infiltrative i-ALCL was 100% and 52.5%, respectively. CONCLUSIONS: In situ i-ALCLs have an indolent clinical course and generally remain free of disease after implant removal. However, infiltrative i-ALCLs could have a more aggressive clinical course that might require additional therapy to implant removal.

A 4-weekly course of rituximab is safe and improves tumor control for patients with minimal residual disease persisting 3 months after autologous hematopoietic stem-cell transplantation: results of a prospective multicenter phase II study in patients with follicular lymphoma.

BACKGROUND: This study explored the efficacy and safety of rituximab as treatment of clinical or molecular residual disease after autologous stem-cell transplantation (ASCT) in follicular lymphoma (FL). PATIENTS AND METHODS: Forty patients with CD20+ FL and clinically (group A, n = 14) or clono-specific PCR-detectable (group B, n = 25) residual disease persisting 3 months after ASCT received rituximab 375 mg/m² once weekly for 4 weeks. RESULTS: Response rate at day 50 was 36% [90% confidence interval (CI) 15-61] in group A (World Health Organization criteria) and 52% (90% CI 34-70) in group B (conversion PCR-undetectable status to undetectable status). The best response rate was 71% [nine complete responses (CRs) and one partial response] in group A and 76% in group B. At 36 months, all 10 responses persisted in group A, whereas 46% of patients in group B still had PCR-undetectable disease. Furthermore, 68% of patients in group B were still in clinical CR. Rituximab after ASCT was safe with few grade 3-4 toxic effects (15% patients), mainly acute reactions and infections. CONCLUSION: Rituximab induced a high rate of durable CRs in patients with clinically detectable disease, as well as durable eradication of PCR-detectable disease in patients with FL after ASCT. Continued molecular responses assessed with a highly sensitive and clono-specific PCR technique were correlated with an excellent disease control.

Elevated levels of PtdIns5P in NPM-ALK transformed cells: implication of PIKfyve.

Phosphatidylinositol 5-monophosphate (PtdIns5P), one of the latest phosphoinositides discovered, has been suggested to play important cellular functions. Here, we report the presence of higher levels of this lipid in cells expressing the oncogenic tyrosine kinase nucleophosmin anaplastic lymphoma kinase (NPM-ALK), a chimeric protein found in the large majority of anaplastic large cell lymphomas (ALCLs). In addition, we describe that a pool of PtdIns5P is located in the membrane extensions characteristic of NPM-ALK-transformed cells. Finally, we show that the increase of PtdIns5P is controlled by the kinase PIKfyve, which is known for its role in vesicular trafficking. These data suggest for the first time a role of PtdIns5P and PIKfyve in oncogenesis, potentially linking intracellular trafficking to cancer.

Powerful strategy for polymerase chain reaction-based clonality assessment in T-cell malignancies Report of the BIOMED-2 Concerted Action BHM4 CT98-3936.

Polymerase chain reaction (PCR) assessment of clonal T-cell receptor (TCR) and immunoglobulin (Ig) gene rearrangements is an important diagnostic tool in mature T-cell neoplasms. However, lack of standardized primers and PCR protocols has hampered comparability of data in previous clonality studies. To obtain reference values for Ig/TCR rearrangement patterns, 19 European laboratories investigated 188 T-cell malignancies belonging to five World Health Organization-defined entities. The TCR/Ig spectrum of each sample was analyzed in duplicate in two different laboratories using the standardized BIOMED-2 PCR multiplex tubes accompanied by international pathology panel review. TCR clonality was detected in 99% (143/145) of all definite cases of T-cell prolymphocytic leukemia, T-cell large granular lymphocytic leukemia, peripheral T-cell lymphoma (unspecified) and angioimmunoblastic T-cell lymphoma (AILT), whereas nine of 43 anaplastic large cell lymphomas did not show clonal TCR rearrangements. Combined use of TCRB and TCRG genes revealed two or more clonal signals in 95% of all TCR clonal cases. Ig clonality was mostly restricted to AILT. Our study indicates that the BIOMED-2 multiplex PCR tubes provide a powerful strategy for clonality assessment in T-cell malignancies assisting the firm diagnosis of T-cell neoplasms. The detected TCR gene rearrangements can also be used as PCR targets for monitoring of minimal residual disease.

Lethal host-versus-graft disease and hypereosinophilia in the absence of MHC I-T-cell interactions.

Neonatal injection of semiallogeneic spleen cells in BALB/c mice induces a self-limited state of chimerism that promotes the differentiation of donor-specific CD4 T cells toward the Th2 phenotype. Here we show that injection of spleen cells from beta2-microglobulin-deficient (BALB/c x C57BL/6) F1 mice into BALB/c newborns with a disrupted beta2-microglobulin (beta2m) gene results in a lethal lymphoproliferative disorder associated with uncontrolled Th2 response, long-term persistence of donor B cells, and sustained blood eosinophilia. Autoimmune manifestations are also enhanced and characterized by a severe autoantibody-mediated glomerulonephritis. Histological examination of the spleen shows a hyperplasia of periarteriolar lymphoid sheaths, with accumulation of eosinophils and basophils, and variable degree of fibrosis. Perivascular lymphoid infiltrates with eosinophils are also found in the lung and are correlated with disease severity. Such abnormalities are almost absent using beta2m-sufficient mice. These data demonstrate that induction of lymphoid chimerism in the absence of MHC class I-T-cell interactions results in a lethal form of host-versus-graft disease that represents a unique model of Th2-dependent chronic inflammatory disease associated with an hypereosinophilic syndrome in mice.

Serpin A1 is overexpressed in ALK+ anaplastic large cell lymphoma and its expression correlates with extranodal dissemination.

Anaplastic large cell lymphoma (ALCL) is a distinct subtype of non-Hodgkin's lymphoma. Most of ALCLs (85%) carry a chromosomal translocation involving different partners in the 5' portion, and the anaplastic lymphoma kinase (ALK) receptor kinase domain in the 3' portion. These translocations induce the ectopic expression of X-ALK proteins, thought to be involved in lymphomagenesis, through the dysregulation of cell proliferation and apoptotic pathways. In the present study, based on several ALK+ and ALK- ALCL cell lines and biopsy specimens, we showed that serpin A1, a secretory glycoprotein, was overexpressed in ALK+ ALCL cell lines and ALK+ tumors at both the transcriptional and translational levels. The crucial role of NPM-ALK in the regulation of serpin A1 expression was further demonstrated by using both ectopic expression and downregulation, by RNA interference, of the NPM-ALK oncogene. In addition, in ALK+ tumors, serpin A1 expression appeared to be correlated with the clinical status of the patients as the serpin A1 mRNA level was higher in patients presenting with extranodal dissemination. These data, together with the pattern of expression of serpin A1 we observed in ALK+ tumors, suggest that serpin A1 has an invasion-promoting effect in ALK+ ALCL.

"In situ-like" mantle cell lymphoma: a report of two cases.

Mantle cell lymphoma (MCL) is a B cell neoplasm that most often shows a diffuse growth pattern. Two cases of MCL are reported here, both with a previous diagnosis of lymphoid hyperplasia. Morphologically, germinal centres are hyperplasic with a normal or discretely enlarged mantle zone, where foci of irregularly shaped small lymphocytes are seen. These are positive for CD20, CD5 and cyclin D1, confirming a diagnosis of in situ-like MCL. This type differs from the mantle zone pattern in that the neoplastic mantle zone is very thin and there is very little or no spread of tumour cells into interfollicular areas. To the best of our knowledge, this is the first report on such a pattern of MCL, which is important to recognise, as it can be confused with lymphoid hyperplasia.

Kisspeptin immunoreactive cells of the ovine preoptic area and arcuate nucleus co-express estrogen receptor alpha.

Kisspeptins are peptide ligands of the G protein-coupled receptor GPR54, recently shown to be essential to reproductive function. We have raised specific rabbit antisera against a highly conserved 10 amino acid-amidated peptide (kp10) common to all kisspeptin isoforms isolated so far and mapped the distribution of kp10-immunoreactive (ir) cells in the ovine hypothalamus. Kp10-ir cells were predominant in the caudal arcuate nucleus, the dorsomedial nucleus and the medial preoptic area. Numerous varicose kp10-ir fibers were found in the preoptic area where GnRH neurons reside and in the median eminence, seemingly projecting around small capillaries in its external zone. Within the caudal arcuate nucleus, nearly all kp10-ir cells showed an intense estradiol receptor alpha immunofluorescent signal compared with approximately half of kp10-ir cells in the preoptic area. The pattern of distribution of kp10 immunoreactivity in the hypothalamus suggests a role for kisspeptin in the estrogen-dependent regulation of GnRH and LH secretion in the ewe.

Nucleolar localization of the nucleophosmin-anaplastic lymphoma kinase is not required for malignant transformation.

The (2;5)(p23;q35) lymphoma-associated chromosomal translocation creates a novel fusion gene that incorporates parts of the anaplastic lymphoma kinase (ALK) receptor tyrosine kinase and nucleophosmin genes. We report here that the product of this fusion gene accumulates within the nucleoli of neoplastic cells, and that previous reports of a predominantly cytoplasmic localization for the protein represent a tissue-processing artifact. However, nucleolar accumulation of nucleophosmin-ALK may not be necessary for its oncogenic action, because an ALK protein expressed in a lymphoma carrying a variant (1;2) chromosomal translocation did not accumulate in nucleoli. Furthermore, an engineered hybrid TPR-ALK protein can transform rodent fibroblasts and produce lymphomas in mice while remaining confined to the cytoplasm. We propose that the transforming action of ALK may not be reliant on its nucleolar localization, a hypothesis that may have implications for studies of other proteins involved in oncogenesis that are relocalized after the creation of fusion genes.

Expression of the oncogenic NPM-ALK chimeric protein in human lymphoid T-cells inhibits drug-induced, but not Fas-induced apoptosis.

Anaplastic large cell lymphomas (ALCLs) are frequently associated with the t(2;5)(p23;q35) translocation, leading to the expression of NPM-ALK, a fusion protein linking nucleophosmin and anaplastic lymphoma kinase, a receptor tyrosine kinase. In ALCLs, dimerization of NPM-ALK leads to constitutive autophosphorylation and activation of the kinase, necessary for NPM-ALK oncogenicity. To investigate whether NPM-ALK, like other oncogenic tyrosine kinases, can inhibit drug-induced apoptosis, we permanently transfected NPM-ALK into Jurkat T-cells. As in ALCLs, NPM-ALK was expressed as a constitutively kinase-active 80 kDa protein, and could be detected by immunocytochemistry in nucleoli, nuclei and cytoplasm. Doxorubicin-induced apoptosis (assessed by cell morphology and annexin V-FITC binding) was significantly inhibited in two independent NPM-ALK-expressing clones (5.2+/-1.8 and 7.5+/-0.8% apoptosis), compared to control vector-transduced cells (36+/-6.7%). Similar results were observed with etoposide. In contrast, Fas-induced apoptosis was not inhibited. Cytochrome c release into the cytosol was delayed in doxorubicin-, but not anti-Fas-treated transfectant cells, indicating that apoptosis inhibition occurred upstream of mitochondrial events. Using NPM-ALK mutants, we demonstrated that inhibition of drug-induced apoptosis: (1) requires functional kinase activity, (2) does not involve phospholipase C-gamma, essential for NPM-ALK-mediated mitogenicity and (3) appears to be phosphoinositide 3-kinase independent, despite a strong Akt/PKB activation observed in wild type NPM-ALK-expressing cells. These results suggest that the NPM-ALK antiapoptotic and mitogenic pathways are distinct.

Mutational hot spots within the carboxy terminal region of the LMP1 oncogene of Epstein-Barr virus are frequent in lymphoproliferative disorders.

We have recently identified in Epstein-Barr virus (EBV) positive Hodgkin's disease (HD) a variant of the latent membrane protein 1 (LMP1) oncogene characterized by four point mutations and a 30 base pair deletion. These findings led us to test whether such mutants were also present in other lymphoproliferative disorders (LPD). We analysed 98 EBV DNA positive cases (67 LPD, 15 benign conditions, 16 lymphoblastoid cell lines) by PCR for deletions within the LMP1 gene. DNA sequencing of the region coding for the carboxy terminal protein domain was performed on 24 cases. In 13 cases the same combination of 4 point mutations at positions 168,320, 168,308, 168,295 and 168,225 was identified. Of these cases, 12 had an additional point mutation at position 168,357 and eight at position 168,355, and nine had a 30 base pair deletion including nucleotides 168,285 to 168,256. These deletion mutants were identified in HD, angioimmunoblastic lymphadenopathy, B-immunoblastic lymphoma, peripheral T-cell lymphoma, and two lymphoblastoid cell lines. Our findings reveal a high frequency of non-random point mutations at preferential sites within the 3' (carboxy terminal) region of the LMP1 oncogene. The association of these mutational hot spots with LPD suggests that they are involved in EBV related lymphomagenesis and that they define a clinically relevant EBV strain.

Lymphocyte-predominant Hodgkin's lymphoma in children: therapeutic abstention after initial lymph node resection--a Study of the French Society of Pediatric Oncology.

PURPOSE: To clarify treatment strategy for lymphocyte-predominant Hodgkin's lymphoma (LPHL), the French Society of Pediatric Oncology initiated a prospective, nonrandomized study in 1988. Patients received either standard treatment for Hodgkin's lymphoma or were not treated beyond initial adenectomy. PATIENTS AND METHODS: From 1988 to 1998, 27 patients were available for study. Twenty-four patients were male, and median age was 10 years (range, 4 to 16 years). Twenty-two, two, and three patients had stage I, II, and III disease, respectively. Thirteen patients (stage I, n = 11; stage III, n = 2) received no further treatment after initial surgical adenectomy (SA). Fourteen patients received combined treatment (CT; n = 10), involved-field radiotherapy alone (n = 1), or chemotherapy alone (n = 3). The two groups were comparable for clinical status, treatment, and follow-up. RESULTS: Twenty-three of 27 patients achieved complete remission (CR). With a median follow-up time of 70 months (range, 32 to 214 months), overall survival to date is 100%, and overall event-free survival (EFS) is 69% +/- 10% (SA, 42% +/- 16%; CT, 90% +/- 8.6%; P <.04). If we considered only the patients in CR after initial surgery (n = 12), EFS was no longer significantly different between the two groups. Patients with residual mass after initial surgery (n = 15) had worse EFS if they did not receive complementary treatment (P <.05). CONCLUSION: Although based on a small number of patients, our study showed that (1). no further therapy is a valid therapeutic approach in LPHL patient in CR after initial lymph node resection, and (2). complementary treatment diminishes relapse frequency but has no impact on survival.

Oestradiol effect on galanin-immunoreactive neurones in the diencephalon of the ewe.

Galanin is a neuropeptide involved in the regulation of numerous functions such as reproduction. In female rats, this peptide stimulates gonadotropin-releasing hormone (GnRH)/luteinizing hormone release and its synthesis is stimulated by oestradiol. It could therefore be an intermediary between the oestrogenic signal from the ovaries and the GnRH neurones (e.g. during the time course leading to the preovulatory GnRH surge). However, although the involvement of galanin is well-known in rodents, it is poorly understood in ewes. Using immunohistochemistry with a specific antigalanin antiserum, we detected the peptide in neurones of two groups of ovariectomized ewes treated for 6 h with subcutaneous implants, either with oestradiol (experimental group) or empty (control group). The galanin-immunoreactive neurones were counted in three areas, the preoptic area, the bed nucleus of the stria terminalis and the infundibular nucleus, using a computerized image analysis system. There was no change in the mean number of galanin-immunoreactive (GAL-ir) neurones in the infundibular nucleus (37 +/- 12 neurones/section in treated animals and 31 +/- 11 in controls) or in the bed nucleus of the stria terminalis (22 +/- 5 neurones/section in treated animals and 16 +/- 4 in controls), but the number of GAL-ir neurones was higher in the preoptic area in treated than in control ewes (35 +/- 4 versus 14 +/- 10, P < 0.001). To determine whether the neurones of the preoptic area were directly sensitive to oestradiol, we performed double immunohistochemical labelling for oestradiol receptor alpha and galanin. More than 50% of the GAL-ir neurones contained the oestradiol receptor alpha and therefore could be directly regulated by oestradiol. These results indicate that oestradiol might act directly on a GAL-ir neuronal population situated in the preoptic area, without any effect on the GAL-ir neurones of the infundibular nucleus or the bed nucleus of the stria terminalis. Because a 6-h oestradiol treatment can induce a preovulatory GnRH surge in ewes, the GAL-ir neuronal population of the preoptic area might be one of the neuronal systems by which oestradiol activates the GnRH neurones. However, although the morphological relationships between galanin and GnRH neurones have been described in rodents, they remain to be demonstrated in the ewe.

Hairy cell transformation of a B-cell chronic lymphocytic leukemia: a morphological, cytochemical, phenotypic and molecular study.

The normal counterparts of the B cells found in hairy cell leukemia (HCL) are not known. We report here a detailed morphological, cytochemical, immunological and molecular analysis of a patient with B-cell chronic lymphocytic leukemia (B-CLL) who later in the course of his disease developed hairy cell leukemia. We speculate that hairy cell transformation of B-CLL might be related to an in vivo protein kinase C mediated cellular activation of B-CLL cells.

B-cell lymphoma following polycythemia vera: evidence for the involvement of two different clones.

We report here two patients with polycythemia vera (PV) who developed secondary non-Hodgkin's lymphoma (NHL). Both cases were high grade B-cell NHL. Cytogenetic analysis of bone marrow and lymph node was performed in each case and showed numerous chromosomal abnormalities. Of interest, chromosomal abnormalities of the PV and of the NHL clones were different, suggesting the possible involvement of two different clones. A 11q23 breakpoint was common between the two cases and the putative role of this breakpoint in the pathogenesis of the NHLs is discussed.

Establishment of a novel anaplastic large-cell lymphoma-cell line (COST) from a 'small-cell variant' of ALCL.

Anaplastic large-cell lymphoma (ALCL) is a distinct biological and cytogenetic entity with a broad spectrum of morphological features (common type, small-cell variant and lymphohistiocytic variant). Few cell lines of ALCL are available and they all originate from primary tumors demonstrating the common type morphology (ie large-sized lymphoma cells). We established a new ALCL cell line (COST) from the peripheral blood of a patient with a small-cell variant of ALCL, at diagnosis. Cells growing in vitro and in SCID mice consisted of two populations, that is, small- and large-sized cells as seen in the patient's tumor. Both large and small malignant cells were positive for CD43/MT1 T-cell associated antigen, perforin, granzyme B and TIA-1, but negative for CD2, CD3, CD5, CD7, CD4 and CD8 antigens. Standard cytogenetic studies as well as multiplex FISH confirmed the presence of the canonical t(2;5)(p23;q35) translocation, but also revealed additional numerical and structural abnormalities. The COST cell line is the first ALCL small-cell variant cell line, and thus provides a potentially useful tool for further functional and molecular studies that should improve our understanding of the small-cell variant of ALCL, which is more frequently complicated by a leukemic phase.

Epstein-Barr virus (EBV) replicative gene expression in tumour cells of AIDS-related non-Hodgkin's lymphoma in relation to CD4 cell number and antibody titres to EBV.

OBJECTIVE: To determine whether activation of Epstein-Barr virus (EBV) replication in tumour cells of AIDS-related non-Hodgkin's lymphoma (ARNHL) is correlated with CD4+ cell counts and influences antibody response to EBV [anti-Z Epstein-Barr replicative activator (ZEBRA), anti-early antigen (EA), anti-viral capsid antigen (VCA)]. DESIGN: Retrospective study based on immunohistochemistry and in situ hybridization to detect EBV replicative gene products in tissue samples from patients affected by ARNHL and correlation with CD4+ cell counts and results of EBV serology (including anti-ZEBRA activity) in sera from the same patients. METHODS: Seventeen out of 22 cases of ARNHL were selected for the presence of EBV [Epstein-Barr early region (EBER) RNA-positive]. Immunohistochemistry was performed with anti-ZEBRA, anti-EA-restricted, anti-VCA antibodies and in situ hybridization with BHLF1/NotI oligoprobes on tumour samples. Results were statistically correlated with those of CD4+ cell counts (17 out of 17) and with anti-EBV antibody titres (13 out of 17) assessed using standard immunofluorescence method and enzyme-linked immunosorbent assay procedure using recombinant ZEBRA protein and synthetic peptides as antigens. RESULTS: BZLF1 (ZEBRA) or early gene products (EA-R and EA-D/BHLF1/NotI) were detected in a small proportion (< 0.01-5%) of tumour cells in eight of these 17 cases by immunohistochemistry and in situ hybridization. Demonstration of replicative gene expression did not correlate with either low CD4+ cell counts (P > 0.05) or anti-EBV antibody titres (P > 0.05). Anti-ZEBRA activity was not significantly increased in patients affected with ARNHL, the cells of which expressed replicative gene products (P > 0.05). CONCLUSION: The degree of immunodeficiency does not clearly enhance replicative gene expression in tumour cells of ARNHL. EBV serology, including anti-ZEBRA activity, is not a reliable tool for predicting the occurrence of such proliferations.

Estrogen synthesis, estrogen metabolism, and functional estrogen receptors in rat arterial smooth muscle cells in culture.

To investigate the mechanisms by which estrogen hormones influence the vascular system, the metabolism of these hormones and the functionality of estrogen receptors were characterized in rat aortic smooth muscle cells from secondary cultures, a widely studied model of vascular biology. Aromatase, estradiol-17 beta-hydroxysteroid dehydrogenase and 17-ketoreductase enzyme activities were demonstrated in these cells. The presence of functional estrogen receptor could also be demonstrated by estrogen-induced transactivating ability in transfection experiments using the luciferase gene reporter and an estrogen responsive element as transcriptional enhancer although the amplitude of the response was only in the range of 140 to 150%. Immunocytochemical analyses, using monoclonal antibodies that recognize epitopes in the A/B domain of the molecule, showed a predominant cytoplasmic localization of these estrogen receptors, even after estrogen addition to the culture medium. Western blot analysis using antibodies that recognize epitopes in the A/B or F domain gave a mol wt of 67,000. Analysis of the estrogen receptor messenger RNA showed that there was no deletion of the proto-signals for nuclear accumulation. The aromatase and dehydrogenase activity results, coupled with the estrogen receptor immunological, RNA analysis, and transfection data strongly support the contention that rat aortic smooth muscle cells are estrogen target cells. This in vitro model is convenient for studying the mechanisms of action of estrogen hormones that seem very peculiar in this cell population.

Telomerase activity in human thyroid carcinomas originating from the follicular cells.

Telomerase activity is known to be absent from most normal and well-differentiated tissues, although being detectable in the vast majority of malignant tumors. An increasing number of reports demonstrate that telomerase may be activated in benign tumors, such as adenomas. We have investigated a series of normal and neoplastic thyroid tissues for the presence of telomerase activity. As expected, all normal thyroid tissues (n = 20) had no display of telomerase activity. Amongst cancers, the incidence of telomerase activity varied with the histological subtypes. Telomerase activity was present in only 3/15 cases (20%) of papillary carcinomas. Telomerase activity was more frequently detected in follicular (4/6) and in undifferentiated (2/3) carcinomas. Unexpectedly, one case (1/12) of adenoma contained high levels of telomerase activity. Taken together, these results indicate that telomerase may play some role in the pathogenesis of thyroid tumors, in particular in follicular and undifferentiated carcinomas that are known to have the most aggressive behavior.

Anaplastic large cell lymphoma of maternal origin involving the placenta: case report and literature survey.

Non-Hodgkin's lymphoma (NHL) occasionally involves the placenta, and information of such occurrence should be useful for management of the mother and fetus. We report the first case of anaplastic large cell lymphoma (ALCL) disseminated to the placenta. The diagnosis was made via excisional biopsy of cervical lymphadenopathy in a 20-year-old woman at 27 weeks' gestation. Involvement of the placenta was noted on gross examination after cesarean section delivery of a girl at 30 weeks' gestation. The ALCL was microscopically confined to intervillous spaces in a manner similar to previous reports of other NHLs. The immunophenotype was characteristic (CD30+, EMA+, BNH9+), and the now frequently associated t(2;5)(p23;q35) translocation with this lymphoma was detected by the recently produced monoclonal antibody ALK1 against the nucleophosmin/anaplastic lymphoma kinase (NPM/ALK) chimeric protein. Complete remission was induced in the mother after delivery. Both mother and child are healthy at 10 years' follow-up. The case is reported in light of the sparse literature on lymphomatous involvement of the placenta.