Masahiro Kikuchi

18F-fluoromisonidazole positron emission tomography before treatment is a predictor of radiotherapy outcome and survival prognosis in patients with head and neck squamous cell carcinoma.

ObjectiveTo evaluate the usefulness of [18F]fluoromisonidazole ([18F]FMISO)-positron emission tomography (PET) prior to the treatment of head and neck squamous cell carcinoma.MethodsSeventeen patients with untreated HNSCC underwent pretreatment [18F]FMISO PET. Six of them underwent definitive surgery and the remaining 11 definitive (chemo-)radiotherapy. We evaluated 30 lesions from the 17 patients. SUVmax and tumor-to-muscle ratios (TMR) were measured as hypoxia indicators. Tumors equal to or above the median value were defined as tumor with high uptake of [18F]FMISO and those below as tumor with low uptake of [18F]FMISO in both indicators. Local control rates with radiotherapy, event-free survival and disease-specific survival (DSS) rates with radiotherapy or operation were compared.Result[18F]FMISO-PET imaging of 30 lesions resulted in a SUVmax median value of 2.3 and a TMR median value of 1.3. Local control rates with radiotherapy (20-month median follow-up duration) were significantly lower in the tumor group with high uptake of [18F]FMISO compared to the tumor group with low uptake of [18F]FMISO using either SUVmax or TMR as the hypoxic indicator (Pxa0=xa00.02 and 0.04, respectively). DSS rate with radiotherapy or operation (21-month median follow-up duration) was significantly lower in the patient group with high uptake of [18F]FMISO compared to the patient group with low uptake of [18F]FMISO defined by SUVmax (Pxa0=xa00.04), but was not by TMR (Pxa0=xa00.57).ConclusionsRadiotherapy outcome and survival prognosis (radiotherapy or operation) in HNSCC may be predicted by carrying out [18F]FMISO PET before treatment.

Infantile digital fibromatosis. Ultrastructural, histochemical, and tissue culture observations

Three cases of infantile digital fibromatosis were studied by electron microscopy, enzyme histochemistry, and tissue culture. The tumors were made up equally of myofibroblasts containing electron‐dense inclusions which were composed chiefly of microfilaments measuring about 5 to 7 nm. Dense bodies usually observable in the smooth muscle cells were found in the bundles of these microfilaments and in the processes of the inclusions, suggesting that these inclusions may represent an abnormal accumulation of contractile protein in the cytoplasm of tumor cells. Two cell lines were established from culture of the tumor cells, and the cultured cells also contained inclusion bodies showing the same morphologic characteristics as those of the original tumor cells. Lysosomal enzymes were abundant in the cultured cells, but they were scant in the cells of the fresh tissue specimens. Cocultivation of the cultured cells with human embryonic lung cells yielded no cytopathic effect.

Lymphoblastic lymphoma expressing natural killer cell phenotype with involvement of the mediastinum and nasal cavity

Most CD56+ lymphomas display polymorphic and angiocentric/angiodestructive histologic features and are closely related to Epstein-Barr virus (EBV) infection. We report a 47-year-old Japanese man with CD56+ lymphoma that showed histologic features of lymphoblastic lymphoma with mediastinal and nasal involvement and an aggressive course. A sample specimen showed the histology of lymphoblastic lymphoma with a positive reaction for terminal deoxynucleotidyl transferase (TdT) but no angiocentric/angiodestructive features. Transmission electron microscopy revealed a few membrane-bound electron-dense granules in their cytoplasm. Immunohistochemically, lymphoma cells exhibited CD56+ cytoplasmic CD3 (cCD3)+ TdT+. A Southern blot analysis showed no integration of EBV and human T-lymphotrophic virus 1 (HTLV-1) and no rearrangement of the T-cell receptors or immunoglobulin heavy chain genes. This unusual lymphoblastic lymphoma exhibiting cCD3 + CD56 + TdT + TCR- is assumed as an immature or progenitor natural killer cell lineage.

Neuropathological and biochemical studies in Fabry's disease

SummaryPathological and biochemical studies were performed on a patient with Fabrys disease. Abnormal deposits in the nervous system were restricted mainly to neurons of the autonomic nervous system. Affected neurons were found in the supraoptic and paraventricular nuclei, the midline nucleus, substriatal grey, nucleus amygdalae, presubiculum of hippocampus, fifth and sixth cortical layers of the parahippocampus and inferior temporal gyrus, dorsal motor nucleus of the vagus, superior and inferior salivatory nuclei, Edinger-Westphal nucleus, reticular formation of the pons and medulla oblongata, trigeminal ganglia, non-pigmented cells of the substantia nigra, intermediolateral column, spinal dorsal root ganglia, sympathetic ganglia and the submucous and myenteric plexuses. Abnormal deposits were found also in the periventricular glial cells, perineurium, the endothelial and smooth muscle cells of blood vessels throughout the body, the heart, kidneys and reticuloendothelial cells of many organs. The histogram of the sural nerve showed a decrease in the smaller myelinated and unmyelinated fibers. The abnormal deposits were glycolipids, CTH and CDH. Although there were two distinct staining characteristics of the deposited material with Luxol fast blue and PAS in paraffin section, these differently stained deposits could not be differentiated by histochemical and biochemical studies.

Angiocentric immunoproliferative lesions of the skin show lobular panniculitis and are mainly disorders of large granular lymphocytes

Eleven patients with angiocentric immunoproliferative lesion (AIL) of the skin were studied. Histologically, three patients were grouped into AIL grade II (AIL-II), whereas eight showed angiocentric lymphoma (AIL-III). All the patients specimens exhibited lobular panniculitis. Infiltrating atypical lymphocytes in nine patients possessed electron-dense membrane bound granules in electron microscopy. Phenotypically, the lymphoid cells in the AIL-II patients were positive for CD3 epsilon; two of these showed a positive reaction to CD2, CD7, and CD8, but lacked natural killer-associated (NKa) antigens CD16, CD56, and CD57. In six AIL-III patients, lymphoma cells were positive for CD2 in all patients, CD56 in five, CD3 epsilon in four, CD7 in four, interleukin-2 beta receptor in four, a pore-forming protein in four, and CD30 in three patients. The remaining two AIL-III patients had B-cell lymphoma. By the Southern blot analysis, three patients with AIL-III showed a rearranged T-cell-receptor beta-gene or a deletion of its germline. The preceding results in nine of 11 patients suggest that abnormal or neoplastic large granular lymphocytes with the characteristics of T and NK cells have an important role in producing the angiocentric/angiodestructive features and lobular panniculitis. Clinically, all three patients with AIL-II and four with AIL-III showed liver dysfunction, cytopenia, and abnormal coagulopathy during the clinical course. Five patients with AIL-III died within 8 months. The histological grading of AIL, patients age, and limited clinical stage of the disease seem to correlate with response to the treatment and prognosis.

Early evaluation of neoadjuvant chemotherapy response using FDG-PET/CT predicts survival prognosis in patients with head and neck squamous cell carcinoma

BackgroundThe purpose of this study was to investigate the possibility of early survival prediction after completion of one cycle of neoadjuvant chemotherapy (NAC) by positron emission tomography (PET)/computed tomography (CT) with 18F-fluorodeoxyglucose (FDG).MethodsFifty-seven patients with advanced head and neck squamous cell carcinoma (HNSCC) underwent FDG-PET/CT scans twice, before and after one cycle of NAC. We calculated the maximal standardized uptake value (SUVmax) for a primary tumor and/or metastatic lymph nodes and defined %decrease as the %difference in SUVmax between the two scans divided by that of the initial scan. Patients were classified as responders by PET (%decrease ≥55.5% or post-NAC SUVmax ≤3.5) and by RECIST (≥30% decrease in size). The local control (LC) rate and the disease-specific survival (DSS) rate were assessed between the responders and non-responders. Multivariate analysis was also performed using the Cox proportional hazards model.ResultsIn univariate analysis, the PET finding of a primary site was a significant risk factor for LC and DSS rates at 2xa0years after completion of NAC (Pxa0=xa00.03 and 0.02, respectively), but there was no difference between responders and non-responders by the RECIST criteria. In a multivariate regression analysis, the PET finding in the primary site and the definitive therapy choice were independent prognostic factors in LC, while the PET finding in the primary site was the only independent prognostic factor in DSS.ConclusionOur preliminary data indicate that the PET finding in the primary lesion after one cycle of NAC was an independent prognostic factor in LC and DSS in patients with HNSCC.

Reduction of [(18)F]fluoromisonidazole uptake after neoadjuvant chemotherapy for head and neck squamous cell carcinoma.

PurposeThe purpose of this study was to investigate the changes of tumor hypoxia as a result of neoadjuvant chemotherapy (NAC) by measuring the changes of [18F]fluoromisonidazole ([18F]FMISO) positron emission tomography (PET) uptake, as well as to look into the ability of [18F]FMISO PET to predict the NAC result.ProceduresA total of 13 patients with locally advanced head and neck squamous cell carcinoma underwent [18F]FMISO PET scans before and after NAC. For analysis of PET index, maximum standardized uptake value, tumor-to-muscle ratio, and hypoxic volume (HV) were measured.ResultsAll PET indexes of [18F]FMISO significantly decreased after NAC. Although HV in primary tumor and a few indexes before NAC in responder was lower than that in nonresponder, none of the indexes were statistically significant.ConclusionsPretreatment [18F]FMISO could not predict NAC outcome in this study. However, [18F]FMISO uptake significantly decreased after NAC, and [18F]FMISO PET seemed to be a useful noninvasive tool for detecting hypoxia reduction after NAC.

TERMINAL DEOXYNUCLEOTIDYL TRANSFERASE STAINING OF MALIGNANT LYMPHOMAS IN PARAFFIN SECTIONS: A USEFUL METHOD FOR THE DIAGNOSIS OF LYMPHOBLASTIC LYMPHOMA

Terminal deoxynucleotidyl transferase (TdT) is a DNA polymerase located in the cell nucleus which catalyses the polymerization of deoxynucleotides at the 3′ hydroxyl ends of oligo‐ or polydeoxynucleotide initiators without a template. TdT is known as a useful marker for the diagnosis of acute lymphoblastic leukaemia/lymphoma, but its detection usually requires fresh tissue specimens or cell suspensions, using either an enzyme analysis or immuno‐fluorescence or ‐peroxidase staining. Until the recent development of the use of microwave‐treated paraffin sections for immunoperoxidase staining, detection of TdT in paraffin sections required rather complicated processes. This new simple technique was applied to paraffin sections from the tumour tissue specimens of 16 patients with lymphoblastic lymphoma and of seven patients with non‐endemic Burkitts lymphoma, which is sometimes difficult to differentiate from lymphoblastic lymphoma because of their similar clinicopathological characteristics. In addition, as a control, ten cases each were examined of adult T‐cell leukaemia/lymphoma (ATLL) and angioimmunoblastic lymphoma (AILD), which are both peripheral T‐cell lymphomas. The tumour cells from 15 of the 16 (94 per cent) patients with lymphoblastic lymphoma were found to be TdT‐positive. The specificity of the anti‐TdT antibody used was confirmed by immunoblot and the specific 60u2009kD band was detected only in a specimen of lymphoblastic lymphoma. These results show that the immunostaining of TdT on paraffin‐embedded sections is a useful method for differentiating lymphoblastic lymphoma from other lymphomas. This method is applicable to a routine diagnostic service.

Sequential FDG-PET/CT after Neoadjuvant Chemotherapy is a Predictor of Histopathologic Response in Patients with Head and Neck Squamous Cell Carcinoma

PurposeTo evaluate whether 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography/computed tomography (FDG-PET/CT) more accurately predicts the histopathologic response to neoadjuvant chemotherapy (NAC) than magnetic resonance imaging (MRI) in patients with head and neck squamous cell carcinoma (HNSCC).ProceduresSixteen patients with HNSCC underwent FDG-PET/CT and MRI scans before and after one cycle of NAC, followed by surgical resection. The 26 surgically resected specimens of the 16 patients were analyzed. Decreases in maximum standardized uptake value (SUVmax) or in tumor maximum size (diametermax) were calculated, and their accuracies for the prediction of histopathologic response were evaluated.ResultsIn histopathologic responders (nu2009=u20097), percent decreases in SUVmax were significantly higher (Pu2009<u20090.001) than in non-responders (nu2009=u200919). Applying a cut-off point of 55.5%, the histopathologic response could be predicted with a sensitivity and specificity of 86% and 95%, respectively.ConclusionFDG-PET/CT can predict histopathologic NAC responses with higher accuracy than MRI in HNSCC patients.

CD30-Positive anaplastic large cell lymphoma in a human T-cell lymphotropic virus-I endemic area

Clinicopathological and cytogenetic studies were performed on specimens from 43 patients with CD30-positive anaplastic large cell lymphoma (ALCL). All patients were born and lived in a human T-cell lymphotropic virus (HTLV)-I endemic area. Twenty-one patients (48.8%) had serum anti-HTLV-I antibody suggesting the presence of adult T-cell leukemia/lymphoma (ATL). Seventeen of them showed a clonal integration of complete HTLV-I proviral DNA by the Southern blot hybridization method in materials obtained by biopsy. Their ages ranged from 37 to 81 years (median, 67.0), and they frequently presented with lymphadenopathy (82.4%) and extranodal tumors with (76.5%) as well as with rare leukemic changes (5.9%). Immunohistologically the lymphoma cells in 15 ATL patients showed a T-cell phenotype. In only one patient (5.9%) was there an expression of epithelial membrane antigen (EMA) in most of the lymphoma cells. Cytogenetically aberration of chromosome band 5q35 was not found in seven patients with HTLV-I proviral DNA. The overall median length of survival was 11.9 months for the patients with HTLV-I proviral DNA, indicating a worse prognosis compared with that of the age-matched patients with negative anti-HTLV-I antibody (P < .01). The specimens of the patients with HTLV-I proviral DNA had unique clinicopathological and cytogenetic features. These findings suggested that T-cell ALCL with HTLV-I proviral DNA should be considered to represent the lymphoma type of ATL.