Syringocystadenoma papilliferum associated with apocrine poroma

A 65-year-old Japanese man presented with a gradually enlarging mass on the right side of the abdomen, which he had first noticed about 4 years previously. He was otherwise asymptomatic. Histopathological examination of the mass revealed an aggregation of neoplastic cells (tumor cell nests) with cellular proliferation extending from the epidermis to the dermis. The tumor consisted of two histologically distinct parts. One part was composed of uniformly small cells with a cuboidal appearance. Some ductal structures were visualized, and some of the cells lining the ductal lumina contained decapitation secretions. These histological changes were consistent with the diagnosis of apocrine poroma. The remaining part of the tumor was composed of cystic invaginations with numerous projections oriented toward the lumen. There were two rows of cells in the projections; the cells on the luminal side were columnar, and those at the apical aspect were small cuboidal cells. These histological changes were characteristic of syringocystadenoma papilliferum (SCAP). Based on these findings, a diagnosis of SCAP associated with apocrine poroma was made. To the best of our knowledge, there have been no previous reports of such a case in the published work.     

Early acral melanoma in situ: correlation between the parallel ridge pattern on dermoscopy and microscopic features

In non-white populations, acral skin is the most prevalent site of malignant melanoma. Early melanomas of this anatomic site are often misdiagnosed as melanocytic nevi, which are not uncommon on acral skin. In fact, clinical and/or histopathological features of melanocytic nevi occasionally mimic those of early acral melanoma and vice versa, and thus differentiation of early acral melanoma from melanocytic nevus is sometimes very difficult for clinicians as well as for histopathologists. Our dermoscopic investigation has revealed that the parallel ridge pattern, a band-like pigmentation on the ridges of the skin markings, is highly specific to malignant melanoma in situ on acral volar skin. In the present study, we reviewed 22 acral melanocytic lesions that showed the parallel ridge pattern on dermoscopy but had very subtle clinical and/or histopathological presentations. We diagnosed 20 of them as early melanoma in situ by careful histopathological examination, which revealed histopathological features very similar to those seen in macular portions of overt acral melanoma, but fundamentally different from features found in melanocytic nevi on acral skin. In correspondence with their dermoscopic pattern, in these early lesions of acral melanomas, proliferation of solitary arranged melanocytes was mainly detected in the crista profunda intermedia, the epidermal rete ridge underlying the ridge of the skin marking. The two remaining lesions were diagnosed as possible cases of acquired melanocytic nevus because of the formation of well-demarcated nests of melanocytes in the epidermal rete ridges. We propose that a finding of preferential proliferation of solitary arranged melanocytes in the crista profunda intermedia is an important clue for the histopathological diagnosis of early phases of acral melanoma.     

Defucosylated anti CC chemokine receptor 4 monoclonal antibody combined with immunomodulatory cytokines: a novel immunotherapy for aggressive/refractory Mycosis fungoides and Sezary syndrome.

PURPOSE: Sézary syndrome (SS) and Mycosis fungoides (MF) in the advanced stage have dismal prognoses. Because CC chemokine receptor 4 (CCR4) has an important role in the skin-homing capacity of MF/SS cells, we postulated that anti-CCR4 monoclonal antibody (mAb) could represent a novel therapeutic agent against aggressive/refractory MF/SS. EXPERIMENTAL DESIGN: The defucosylated next-generation therapeutic mAb KM2760 induces enhanced antibody-dependent cellular cytotoxicity (ADCC). Here, we assessed the therapeutic potential of this antibody against aggressive MF/SS tumor cells in vitro and in animal models in vivo. RESULTS: KM2760 induced robust ADCC by peripheral blood mononuclear cell (PBMC) from healthy controls against a MF/SS cell line as well as against primary tumor cells from patients with aggressive MF/SS. KM2760 also showed significant antitumor activity in disseminated and nondisseminated MF/SS mouse models. In addition, approximately 30% of autologous MF/SS tumor cells were killed in in vitro assays of KM2760-induced ADCC mediated by patients' PBMC after only 4 h, despite the low numbers of natural killer cells present in these PBMCs. It is also shown that ADCC induced by defucosylated therapeutic mAb can be greatly augmented by the immunomodulatory cytokines interleukin-12, IFN-alpha-2b, and IFN-gamma. CONCLUSIONS: The present study has encouraged us in the conducting of a phase I clinical trial of a completely defucosylated anti-CCR4 mAb in patients with CCR4-positive T-cell lymphomas, including aggressive MF/SS (ClinicalTrials.gov identifier: NCT00355472). In the near future, the efficacy not only of defucosylated anti-CCR4 mAb single-agent treatment but also of combination therapy with immunomodulatory cytokines will be clinically established to target aggressive/refractory MF/SS.     

Development of an assessment sheet for fall prediction in stroke inpatients in convalescent rehabilitation wards in Japan

Objective We conducted a study to develop an assessment sheet for fall prediction in stroke inpatients that is handy and reliable to help ward staff to devise a fall prevention strategy for each inpatient immediately upon admission. Methods The study consisted of three steps: (1) developing a data sampling form to record variables related to risk of falls in stroke inpatients and conducting a follow-up survey for stroke inpatients from their admission to discharge by using the form; (2) carrying out analyses of characteristics of the present subjects and selecting variables showing a high hazard ratio (HR) for falls using the Cox regression analysis; (3) developing an assessment sheet for fall prediction involving variables giving the integral coefficient for each variable in accordance with the HR determined in the second step. Results and discussion (1) Subjects of the present survey were 704 inpatients from 17 hospitals including 270 fallers. (2) We selected seven variables as predictors of the first fall: central paralysis, history of previous falls, use of psychotropic medicines, visual impairment, urinary incontinence, mode of locomotion and cognitive impairment. (3) We made 960 trial models in combination with possible coefficients for each variable, and among them we finally selected the most suitable model giving coefficient number 1 to each variable except mode of locomotion, which was given 1 or 2. The area under the ROC curve of the selected model was 0.73, and sensitivity and specificity were 0.70 and 0.69, respectively (4/5 at the cut-off point). Scores calculated from the assessment sheets of the present subjects by adding coefficients of each variable showed normal distribution and a significantly higher mean score in fallers (4.94 ± 1.29) than in non-fallers (3.65 ± 1.58) (P = 0.001). The value of the Barthel Index as the index of ADL of each subject was indicated to be in proportion to the assessment score of each subject. Conclusion We developed an assessment sheet for fall prediction in stroke inpatients that was shown to be available and valid to screen inpatients with risk of falls immediately upon admission.     

Diffuse pulmonary arteriovenous fistula shown by contrast echocardiography and pulmonary angiography

We report an 11-year-old boy with diffuse pulmonary arteriovenous fistula (multiple telangiectasia type). Contrast echocardiography proved R to L shunting at the peripheral levels of the lungs. A definitive diagnosis was obtained by pulmonary arteriography.     

Early infectious complications after peripheral blood stem cell autografts in children

Seventeen children underwent marrowablative high-dose chemotherapy with peripheral blood stem cell autografts and were studied retrospectively to determine the type, frequency, and outcomes associated with infectious complications 3 months postgraft. The patients were kept in isolated rooms with a laminar air flow facility, but no decontamination procedures, such as gut sterilization with nonabsorbable antibiotics, nonmicrobial diet, and skin cleansing, were used. They were under their mothers' daily care to maintain good psychological conditions. After the completion of marrow-ablative chemotherapy and the infusion of stem cells, the absolute granulocyte count exceeded 0.5 × 10⁹/liter with a mean of 17.9 days (range 6–65 days), Fifteen patients developed a total of 16 febrile episodes during the first 4 week period, and the confirmed diagnoses were mucositis (12), enterocolitis (nine), septicemia (four), central venous catheter-associated infection (three), pneumonia (one), perianal abscess (one), and possible invasive fungal infection (one). All episodes were successfully treated with parenteral antibiotic therapy, and no patient died of infectious complications. The observations suggest that high-dose chemotherapy can be performed safely with simple and efficient patient management protocol followed by peripheral blood stem cell autografts.     

Acute Lymphoblastic Leukemia in a Patient with Pituitary Dwarfism under Treatment with Growth Hormone

An 18-year-old male with pituitary dwarfism, who had been on replacement of growth hormone (GH) and thyroxine for 3.5 years, developed acute lymphoblastic leukemia (ALL). The GH replacement was discontinued, and he was treated with a conventional protocol for ALL. A complete remission was obtained after 10 weeks. Maintenance chemotherapy was given with reduced doses (1/4 to 1/2) of cytotoxic drugs. The platelet count soon reached 200,000/μL, but the hemoglobin level and white blood cell count improved only slowly, reaching 10.0 g/dL and 1,500/μL, respectively, after five months. He has been in complete remission with a hypocellular bone marrow for nearly 15 months. Since GH can stimulate the proliferation of some normal and leukemic hemato-lymphoid cells, the slow remission induction and the prolonged anemia and leukocytopenia after remission, may have been related to the absence of GH in this patient.     

Pseudo-Chediak-Higashi Anomaly in Acute Myeloid Leukemia (M2) of Childhood

The frequency and clinical significance of the pseudo-Chediak-Higashi (PCH) anomaly were studied in 20 children with acute myeloid leukemia (AML) M2 in the FAB nomenclature. PCH granules were recognized as giant eosinophilic granules, measuring up to 5μ, in the cytoplasm of leukemic cells on smears. At the electron microscope level, most PCH granules were round to oval and outlined by a limiting membrane, and contained homogeneous, granular, crystalloid, rod-like or myelin-like materials. The PCH anomaly was demonstrable in five (25.0%) of the 20 patients, which indicates that the anomaly is not rare in childhood AML M2. There were no differences between PCH anomaly-positive and PCH anomaly negative groups with regard to hepatosplenomegaly, hemoglobin levels, white blood cell counts, bone marrow cellularity, t(8q-, 21q+) chromosome abnormalities or prognoses. Circulating leukemic cells were observed less frequently in the PCH anomaly-positive group than in the PCH anomaly-negative group (p <0.05); the leukemic cells were not demonstrable in three of the five patients in the former group, although they were detected in all 15 patients in the latter group. The existence of PCH granules and/or a defect of the cytoskeleton responsible for the PCH anomaly in leukemic cells may impede their movement from the bone marrow to the peripheral blood.