Kayoko Higuchi

Mouse senile amyloidosis : ASSAM amyloidosis in mice presents universally as a systemic age-associated amyloidosis

SummaryAmyloid deposition in 11 inbred strains of mice (A/J, SJL/J, DDD, C57BL/6J, B10.BR, C57BL/10, Bl0A/SgSn, C3H/HeMs, B10A(5R), DBA/2 and C57BL/6Cr5/c) was studied using the peroxidase antiperoxidase (PAP) method and antisera against ASSAM and murine protein AA. Among the 170 mice examined, in 77 (45.3%) from the nine strains other than C3H/ HeMs and DBA/2, there was evidence of spontaneous amyloid deposits in routine histological sections. Immunohistochemical studies using 54 mice with amyloid deposition, demonstrated ASSAM deposition in 45 mice (83.3%) in all nine strains, although the incidence and intensity of the deposition differed somewhat between strains. SJL/J and A/J had ASsam deposits from the age of 8 months and the incidence increased with advancing age. In the other seven strains, ASSAM was first deposited at an older age than in the SJL/J and A/J strains. In A/J, C57BL/6J, C57BL/10, B10.BR, B10A(5R) and C57BL/6Cr5/c, protein AA often coexisted with ASSAM The distribution pattern of the ASSAM deposits was similar to that observed among the SAM strains. Thus, ASSAM is an ubiquitously distributed senile amyloid protein in the mouse. Determination of the molecular type of apoA-II, a serum precursor of ASSAM, among all 11 strains using the polymerase chain reaction (PCR) revealed the SAM-P/1 type apoA-II variant in SJL/J and A/J strains with a high susceptibility to ASSAM deposition. We concluded from this study that amino acid substitution in precursor apoA-II may be responsible for the early onset and severe amyloid deposition in the mouse.

Immunohistochemical Distribution of CA19-9 in Normal and Tumor Tissues of the Kidney

The immunohistochemical distribution of CA19-9 in normal and tumor tissue of the kidney was investigated. CA19-9 was detected in the cytoplasm and apical surface of renal proximal tubules, distal tubules and uroepithelium of the renal pelvis. Eight of 28 renal cell carcinomas (29%) expressed CA19-9. CA19-9 was also detected in 2 cases of transitional cell carcinoma and 1 of 4 cases of Wilms tumor, but not in angiomyolipoma. As the measurement of CA19-9 is widely used to detect gastrointestinal carcinoma, the expression of CA19-9 in normal and neoplastic kidney tissue might have some clinical significance.

Salivary duct carcinoma: A clinicopathologic study of three cases with a review of the literature

Three cases of salivary duct carcinoma are presented. They occurred in a 60 year old man, a 66 year old man and a 57 year old woman. All of the lesions were located In the parotid gland. The tumor size ranged from 3 to 5 cm across the largest diameter. Facial paralysis was observed in two cases. Histologically, intreductal and invasive adenocarcinoma showing papillary, cribriform, and solid patterns with comede like necrosis was observed. lmmunohistochemically, the tumor cells were positive for keratin and epithelial membrane antigen. No myoepithelial cells were demonstrated within the tumor by staining for S‐100 protein, α‐smooth muscle actin or muscle specific actin. Ultrastncturally, intracytoplasmic lumina with microvilli, a moderate number of mltochrondria, lysosomes, and tight junctions were found. Regional lymph node metastasis was observed in one case, and distant metastasis developed in two cases. All of me patients were treated with adjuvant postoperative irradiation. One patient died of disease at 11 months after the initial diagnosis, another was alive with disease at 8 months, and the third patient was alive without disease at 2 years and 3 months. Salivary duct carcinoma should be ditterentiated from low‐grade salivary gland carcinomas using morphologic and clinical criteria because of its poor prognosis even with aggressive therapy.

A case of anaplastic lymphoma kinase (ALK)-positive ciliated muconodular papillary tumor (CMPT) of the lung

Ciliated muconodular papillary tumor (CMPT) is a rare papillary tumor that arises in the peripheral lung fields and is associated with the proliferation of ciliate d and goblet cells and increased mucin production. We report a case of CMPT involving the rearrangement of the anaplastic lymphoma kinase (ALK) gene. The patient was an 84‐year‐old Japanese female who had exhibited a small nodular shadow on chest computed tomography during a regular checkup 10 years ago. She underwent a partial resection of segment S10 of the right lung. The cut surface of the surgical specimen revealed a well‐circumscribed, jelly‐like mass measuring 8 × 8 × 10 mm. Histologically, the tumor was composed of a mixture of ciliated, goblet, and basal cells arranged in a papillary pattern together with pools of mucin. A diagnosis of CMPT was made. The lung tumor cells were subjected to fluorescent in situ hybridization and highly sensitive immunohistochemical staining for the ALK protein, both of which produced positive results. CMPT usually follows a favorable course, but the exact nature of this tumor; i.e., whether it is benign or malignant, has not been established. This is the first reported case of an ALK‐positive CMPT.

Serum amyloid A expression in the breast cancer tissue is associated with poor prognosis

Background Serum amyloid A (SAA), an acute-phase protein, is expressed primarily in the liver, and recently found also expressed in cancer tissues. However, its expression and prognostic value in breast cancer have not been described. Results SAA protein was found expressed in tumor cells in 44.2% cases and in TAM in 62.5% cases. FISH showed more frequent SAA mRNA expression in TAM than in tumor cells (76% versus 12%, p < 0.001), and a significant association between the frequencies of SAA mRNA expression in TAM and tumor cells (rs = 0.603, p < 0.001). The immunoreactivities of SAA protein in TAM and tumor cells were both associated with lymphovascular invasion and lymph node metastasis. Moreover, SAA-positivity in TAMs was associated with larger tumor-size, higher histological-grade, negative estrogen-receptor and progesterone-receptor statuses, and HER-2 overexpression. It was also linked to worse recurrence-free survival in a multivariable regression model. Methods Immunohistochemistry was applied on the tumor tissues from 208 breast cancer patients to evaluate the local SAA-protein expression with additional CD68 stain to identify the tumor-associated macrophage (TAM) on the serial tissue sections. Fluorescent in situ hybridization (FISH) was conducted on serial tissue sections from 25 of the 208 tumors to examine the expression and location of SAA mRNA. Conclusions Our results suggested that the TAMs may be a pivotal and main source of SAA production in tumor microenvironment of breast cancer. SAA immunoreactivity in TAM is associated with worse recurrence-free survival, and is therefore a biomarker candidate for postoperative surveillance and perhaps a therapeutic target for breast cancer.

Glial cyst of the pineal gland with characteristic computed tomography, magnetic resonance imaging, and pathological findings: Report of two cases

Two cases of glial cyst of the pineal gland are documented. Preoperative computed tomography and magnetic resonance imaging revealed cystic lesions of the pineal region with contrast enhancement of the walls, suggesting neoplastic lesions rather than true cysts. However, the histopathological examination of the resected specimens revealed the presence of glial tissue and normal structure of pineal gland and capsule, characteristics that were consistent with those of glial cysts of the pineal gland. Headache and visual disturbance were resolved after total removal of the cysts.

Undifferentiated carcinoma of the thyroid gland : sonographic findings

We report high resolution sonographic (7.5 MHz) findings in four cases of undifferentiated carcinoma of the thyroid gland. Sonographic findings in these four cases included poorly marginated, hypoechoic masses associated with calcifications, and invasion of adjacent cervical structures. A knowledge of the sonographic features of undifferentiated carcinoma of the thyroid gland is of clinical importance, since the tumour has a grave prognosis, quite different from the relatively favourable prognosis of well differentiated thyroid carcinoma.

Cytology of three cases of salivary duct carcinoma

背景:唾液導管癌 (Salivary duct carcinoma) は比較的まれな高悪性唾液腺腫瘍である. 耳下腺に発生した唾液導管癌3例の穿刺吸引細胞像を報告する.症例:症例1;49歳, 男性.左耳下腺腫瘍. 穿刺吸引細胞像では, 壊死物質とともに結合性が強く節状構造を示す上皮性大細胞集団を認めた. 細胞は多辺形から円柱形の豊富で厚い細胞質を有し, まれにintracytoplasmiclumina (ICL) を認めた. 核は遍在傾向を示し円形から楕円形で細顆粒状のクロマチンを有し, 腫大した核小体を認めた. 症例2;76歳, 男性. 左耳下腺腫瘍. 細胞像では壊死物質を背景に結合性が低下した充実性の上皮性細胞集団を認めた. 細胞の細胞質は厚く, 核細胞質比は高く, 核の配列不整や核小体の腫大が目立った. 症例3;66歳, 男性. 右耳下腺腫瘍. 細胞像ではきれいな背景中に結合性の低下した上皮性集塊が少量認められた. 腫瘍細胞は多辺形で顆粒状の細胞質を有し, 変性のため核が濃縮状で核細胞質比が低かった.結論:唾液導管癌の細胞診断では, 典型的な細胞像とともに症例間の細胞像の差異や壊死による細胞像の変化も念頭におくことが重要と考えられた.

A New Senile Amyloid Fibril Protein and Its Putative Precursor in Senescence Accelerated Mouse (SAM)

A new amyloid fibril protein was isolated from the livers of Senescence Accelerated Mice (SAM-P), a strain characterized by accelerated senescence and a high incidence of age-associated systemic amyloidosis. This 5,200 dalton amyloid protein “ASSAM” differs in amino acid composition from the amyloid protein of murine secondary amyloidosis. Sequence analysis revealed a blocked N-terminus. Double immunodiffusion tests showed no relationship between ASSAM and murine protein AA or immunoglobulin components.