Masayuki Shintaku

Cyclin-D1-gene amplification is a more potent prognostic factor than its protein over-expression in human head-and-neck squamous-cell carcinoma.

To evaluate the prognostic significance of cyclin D1 protein/gene expressions in human head‐and‐neck squamous‐cell carcinoma (HNSCC), we examined amplification of the cyclin‐D1 gene (CCND1) by the differential PCR method and over‐expression of cyclin‐D1 protein by immunohistochemistry in 45 paraffin‐embedded sections from HNSCC. Amplification of CCND1 was found in 10 (22%) cases and over‐expression of cyclin D1 was found in 24 (53%) cases. CCND1 amplification was also found in 3 (25%) of 12 cases of dysplastic lesions adjacent to HNSCC. The overall 5‐year survival of patients with CCND1 amplification or with protein over‐production was significantly lower than that of patients without (p < 0.0001 and p < 0.05, respectively). However, with multivariate analysis, only amplification of CCND1 retained an independent prognostic value (p = 0.0018). These suggest that CCND1 amplification occurs at early stages of HNSCC tumorigenesis and is a more useful prognostic factor than over‐expression of cyclin D1 in HNSCC. Int. J. Cancer 74:576–581, 1997.© 1997 Wiley‐Liss, Inc.

Lymphoproliferative disorders in autoimmune diseases in Japan: analysis of clinicopathological features and Epstein-Barr virus infection.

Lymphoproliferative disorders (LPD) occasionally develop in individuals with immune deficiencies such as immunosuppressive conditions and autoimmune diseases (AID). In our study, the clinicopathologic features and virus status were analyzed in 53 cases with LPD developing in rheumatoid arthritis (RA) and other AID. AID in only 4 of 53 patients had been treated with some sort of immunosuppressive therapy, including methotrexate. Median age at the diagnosis of LPD in AID was 60 years old with marked female predominance (M/F = 0.4). The median interval between the onset of AID and LPD development was 45 months, and longer in RA patients than in other AID (p < 0.01). The primary site of lymphoma was nodal in 21 cases and extra‐nodal in 24, with clinical Stage I in 17, II in 5, III in 13, and IV in 13. Immunohistochemistry showed that 39 cases were B cell type, 10 were T cell type and 4 were Hodgkin lymphoma (HL). Then majority of B cell cases were diffuse large B cell lymphomas, and 2 were diffuse polymorphic type. EBER‐1 in situ hybridization for Epstein‐Barr virus (EBV) showed positive signals in tumor cells in 16 of 53 (30.2%) cases. The EBV‐positive rate in T cell LPD (70%) was much higher than that in B cell LPD (12.8%) (p < 0.01). All 4 cases of HL were EBV‐positive. Immunohistochemistry showed a latency II pattern of EBV infection (LMP‐1+ and EBNA‐2−). Five‐year overall survival rate was 33%. Multivariate analysis showed that only type of AID was an independent factor for survival of patients, i.e., LPD in RA showed the most favorable prognosis. In conclusion, LPD in AID generally shared common features with sporadic LPD except for a much higher EBV‐positive rate in T cell LPD.

Prognostic significance of tumor/stromal caveolin-1 expression in breast cancer patients

Caveolin‐1 (Cav‐1) has been extensively characterized in cancer biological research. However, the role of Cav‐1 in the interaction between tumor and stromal cells remains unclear. In the present study, we examined Cav‐1 expression in tumor cells and stromal cells in breast cancer tissue by immunohistochemical analysis and evaluated its prognostic value in a training cohort. Immunohistochemical analysis of Cav‐1 expression was scored as (++), (+) or (−) according to the proportion of positively stained tumor cells (T) and stromal cells (S). Correlation analysis between tumor/stromal Cav‐1 expression and clinicopathological parameters revealed that only T(++) Cav‐1 status was positively associated with tumor size and histological nodal status (P = 0.019 and 0.021, respectively). Univariate analysis revealed that combined T(++)/S(−) status was significantly correlated with unfavorable prognostic outcomes (P < 0.001). Multivariate analysis demonstrated that this combined status is an independent prognostic factor for primary breast cancer (P = 0.002). Clinical outcomes in different subgroups of breast cancer patients were also strictly dependent on this combined status (P < 0.05). The prognostic value of T(++)/S(−) Cav‐1 status was also validated in the testing cohort. Collectively, our data indicate that high Cav‐1 expression in tumor cells and lack of this expression in stromal cells could help identify a particular subgroup of breast cancer patients with potentially poor survival. Further studies are required to understand the regulatory mechanism of Cav‐1 in the tumor microenvironment. (Cancer Sci 2011; 102: 1590–1596)

Dense-type crypt opening seen on magnifying endoscopy with narrow-band imaging is a feature of gastric adenoma

Magnifying endoscopy with narrow‐band imaging (ME‐NBI) can visualize crypt openings (CO) as slit‐like structures in gastric epithelial neoplasia. Visualization of numerous CO is characteristic of low‐grade adenoma (LGA). The aim of the present study was to investigate whether visualization of CO by ME‐NBI is useful for discriminating between LGA and early gastric cancer (EGC).

Malignant Peripheral Nerve Sheath Tumor with Fibroblastic Differentiation in a Patient with Neurofibromatosis Type 1: Imprint Cytological Findings

Background: Malignant peripheral nerve sheath tumor (MPNST) is a heterogeneous group of neoplasms that shows divergent differentiation potential, and the cytological findings are largely nonspecific. There are no previous reports specifically alluding to the cytological findings of MPNST showing fibroblastic differentiation (fibroblastic MPNST). Case: A 59-year-old woman with neurofibromatosis type 1 developed a rapidly enlarging tumor on the scalp. A metastatic lesion in the ileum was examined cytologically. Irregularly shaped clusters of spindle cells with wavy or buckled nuclei and fibrillary cytoplasm were found as well as many similar isolated cells. Histopathologically, the tumor showed a spindle cell sarcomatous appearance typical of MPNST. Immunohistochemically, the tumor cells were negative for S-100 protein and epithelial membrane antigen but immunoreactive for vimentin, CD10 and CD34. Ultrastructurally, the tumor cells were not invested by the basal lamina and had abundant rough-surfaced endoplasmic reticulum and a subplasmalemmal accumulation of microfilaments with dense patches. These immunohistochemical and ultrastructural findings were consistent with fibroblastic or myofibroblastic differentiation. Conclusion: Although there are no cytological findings specific for fibroblastic MPNST, the wide spectrum of differentiation in MPNST should be kept in mind during cytological examination of soft tissue sarcomas.

A case of rare primary cystic-type squamous cell carcinoma of the breast that could be preoperatively diagnosed

Primary squamous cell carcinoma of the breast (SCCB) is a rare disease, with a worldwide incidence <0.1%. In many cases, it is clinically characterized by rapid growth. Cyst formation due to central necrosis of the tumor accompanies its growth of the tumor in approximately 60-80% of all cases. Furthermore, it is considered difficult to diagnose SCCB solely on the basis of findings from diagnostic imaging. For large intracystic tumors, mammotome biopsy or core needle biopsy (CNB) is rarely performed. Instead, fine-needle aspiration (FNA) targeted at the tumor inside the cyst is often performed. The accurate diagnosis rate of SCCB using FNA is lower than that for ordinary-type breast cancer. If the cyst is large, the solid tumor shadow outside the cyst behind or around the cyst may be masked or hidden by the large cyst, which can sometimes yield an unclear view of the tumor shadow or make it impossible to visualize the shadow. In the present case, the contents within the cyst were completely aspirated and collected during the first step (FNA), thereby yielding a clearer, complete view of the solid tumor located outside the cyst. Thus, the subsequent step (CNB) was able to be performed in a more accurate and reliable manner. The combined use of FNA and CNB proved to be useful in making a preoperative diagnosis of SSCB accompanying a cyst.

Active opening and closing movements of the orifices of esophageal intramural pseudodiverticulosis

F u B S Esophageal intramural pseudodiverticulosis (EIPD) is a rare disorder in which many small pouches are formed within the esophageal submucosa. On endoscopic examination, the orifices of these pouches are observed as small holes on the mucosal surface. The disease was first described by Mendl et al,1 and histopathological examination of subsequent cases disclosed that these pouches consist of dilated ducts of the submucosal glands.2-4 During enoscopic examination of the esophagus of a patient with IPD, we observed for the first time active opening and losing movements of the mucosal orifices of EIPD.

CD30+ pseudolymphoma arising on the lower lip.

Figure 1. (a) A hard nodule with ulcerative surface was seen on the right side of the lower lip. (b) After 1 month, the lesion disappeared spontaneously leaving no scar formation. Dear Editor, Cutaneous pseudolymphoma was first described under the term sarcomatosis cutis by Kaposi in 1891, and the term was mainly used to describe cutaneous B-cell pseudolymphoma. After the report of actinic reticuloid in 1969, cutaneous pseudolymphoma included types of lesions due to T-cell proliferation. Today, the entity of pseudolymphoma generally includes benign but lymphoma-like cutaneous proliferations of lymphocytes caused by trauma, intake of drugs, contact with chemicals, arthropod-bite reactions, light reaction and unknown causes. We recently encountered a patient with a nodule on the lower lip showing tumorous proliferation of CD30 cells closely mimicking lymphoma. In contrast with the histology, the skin lesion spontaneously regressed within a short time. A 35-year-old woman without any remarkable past history including taking drugs noticed a small flat nodule on the right side of the lower lip approximately 1 month prior to the first consultation, when the nodule enlarged to form a hard eruption measuring 10 mm · 12 mm. The surface of the nodule was irregularly ulcerated with a crust-like necrotic mass, and the margin of the ulcer was elevated (Fig. 1a). Punch biopsy performed from the elevated margin demonstrated a dense and thick proliferation of mononuclear cells under a necrotic epidermis (Fig. 2a). Proliferating mononuclear cells in the upper two-thirds of the lesion showed large pale ovoid nuclei and prominent cytoplasm, resembling histiocytes (Fig. 2b). In the lower one-third portion of the proliferation, lymphoid cells were scattered among proliferating histiocytoid cells (Fig. 2c). Nuclear atypism was not clear, but coexisting mitotic figures strongly suggested that the lesion was malignant lymphoma or a kind of histiocytosis. Immunoperoxidase staining demonstrated that the proliferating mononuclear cells were negative for cytokeratins

Brushing Cytology of the Biliary Tract: Bile Juice from the ERCP Sheath Tube Provides Cell-Rich Smear Samples

Objectives: To improve the diagnostic accuracy of bile smear cytology, we assessed two cell-yielding procedures. Study Design: One hundred and forty-one patients with biliary stricture underwent endoscopic retrograde cholangiopancreatography (ERCP) and conventional brush sampling. The cytologist cut the brush head off the support wire, centrifuged it directly in tissue culture medium for 1 min at 3,000 rpm, centrifuged the medium again and then smeared the cell pellet onto slides. The remaining sheath tube was then cut into 12-cm segments, which were centrifuged in a centrifuge tube for 1 min at 3,000 rpm, collected and submitted for cytospin preparation. Results: The final histopathological diagnoses based on surgery, biopsy or clinical progression were evaluated for sensitivity, specificity and accuracy. Using conventional smears alone, the sensitivity, specificity and accuracy in patients with biliary stricture were 66.1, 80.7 and 68.8%, respectively. For conventional smears, brush washing and sheath tube contents together, the sensitivity improved to 73.9%, specificity to 100% and accuracy to 78.7%. In the patients with bile duct carcinoma, the sensitivity, specificity and accuracy were 87.3, 100 and 90.7%, respectively. Conclusion: Superior diagnostic accuracy was achieved when conventional smear procedures were combined with the two new procedures.

Front & Back Matter

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