Mikinao Oiwa

Suppressive effect of iodine on DMBA-induced breast tumor growth in the rat

Concerning the suppressive effect of inorganic iodine on the growth of 7,12‐dimethyl‐benz(a)anthracene (DMBA)‐induced breast tumor in female Sprague‐Dawley (SD) rats, we previously reported that although iodine itself had a suppressive effect on the tumor growth, its effect was not as strong as that of MPA (medroxy‐progesterone acetate). However, the combined medication of iodine at a low concentration + MPA showed a stronger effect than MPA alone. The purpose of the present study is to elucidate this mechanism of action by determining the uptake of the administered iodine into breast tumor tissue. Breast tumors were induced with DMBA in female SD rats, and these animals were treated with MPA + inorganic iodine at various concentrations for 4 weeks to determine tumor growth and tumor iodine content. In the comparison of tissue iodine content in growth‐suppressive tumors with that in nonsuppressive tumors, the former showed a much higher iodine content. This suggests that direct uptake of inorganic iodine by breast tumors led to the suppression of tumor growth.

Parathyroid autotransplantation with total thyroidectomy for thyroid carcinoma: Long-term follow-up of grafted parathyroid function

BACKGROUND Permanent hypoparathyroidism is a major complication of thyroidectomy. Autotransplantation of parathyroid glands has been attempted to prevent this complication. However, no direct data have been available to assess grafted parathyroid function after long-term follow-up in terms of the serum intact parathyroid hormone (PTH) concentration. METHODS Eighty-four consecutive patients with differentiated thyroid carcinoma who underwent total thyroidectomy and bilateral modified neck dissection from 1992 to 1996 were enrolled. They concomitantly underwent total parathyroidectomy and autotransplantation of all parathyroid glands to the pectoralis major muscle. The serum intact PTH concentration was periodically measured as an index of grafted parathyroid function. RESULTS The mean follow-up was 34 months. In all autotransplanted patients serum intact PTH concentrations fell below detectable limits immediately after surgery. They were restored to the normal range within 1 month postoperatively and were maintained during observation in 80 (95%) of 84 patients. Seventy-eight of 80 patients with normal intact PTH values were normocalcemic without any treatment and the remainder were normocalcemic with 1 microgram of 1 alpha-vitamin D3. Four hypoparathyroid patients were normocalcemic with 2 micrograms of 1 alpha-vitamin D3. The postoperative average serum intact PTH concentration of patients having more than 2 autotransplanted parathyroid glands was almost equal to that of patients with preservation of the parathyroid glands in situ. The incidence of permanent hypoparathyroidism was inversely correlated with the number of autotransplanted parathyroid glands. CONCLUSIONS The recovery patterns of the intact PTH concentration indicate that the glands were grafted successfully and functioned for a long period. This feasible method of parathyroid autotransplantation bears comparison with the previous reports in terms of the incidence of permanent postoperative hypoparathyroidism, and it can be performed simply and is reproducible.

Intracytoplasmic lipid accumulation in apocrine carcinoma of the breast evaluated with adipophilin immunoreactivity: a possible link between apocrine carcinoma and lipid-rich carcinoma.

Although apocrine carcinoma is a distinct histologic entity, there is no immunohistochemical marker to confirm apocrine differentiation with high sensitivity and specificity, and its differential cytologic characteristics are still not fully clarified. Despite the foamy cytoplasm of some apocrine carcinomas and the existence of lipid in the normal apocrine gland, intracytoplasmic lipid in apocrine carcinomas has not been fully explored. By using immunohistochemistry for adipophilin, which is a specific marker of lipid accumulation that can be applied to paraffin sections, we examined intracytoplasmic lipid in apocrine carcinomas. Twenty-four of 26 (92%) apocrine carcinomas and 38 of 116 (33%) nonapocrine carcinomas contained intracytoplasmic lipid. The frequency of adipophilin-positive cases was significantly higher in apocrine carcinomas compared with nonapocrine carcinomas (P<0.01). The positive cell rate per tumor ranged from 10% to 70% (mean, 29%) for apocrine carcinomas. The staining density was heterogeneous from cell to cell. There was no difference in the staining pattern of adipophilin between apocrine ductal carcinoma in situ and invasive apocrine carcinoma or between eosinophilic cells and foamy cells. Sporadic or mosaic distribution of adipophilin-positive cells throughout the tumor and microvesicular or fine granular cytoplasmic staining with heterogeneous density were characteristic features of apocrine carcinoma. Although intracytoplasmic lipid was identified in most apocrine carcinomas, none of the apocrine carcinomas contained prominent intracytoplasmic lipid in >90% of the tumor cells; thus, the criteria for lipid-rich carcinoma was not fulfilled. However, the immunohistochemical study suggests that lipid-rich carcinomas are closely related to apocrine carcinomas.

Topographical, morphological and immunohistochemical characteristics of carcinoma in situ of the breast involving sclerosing adenosis. Two distinct topographical patterns and histological types of carcinoma in situ.

Moritani S, Ichihara S, Hasegawa M, Endo T, Oiwa M, Shiraiwa M, Nishida C, Morita T, Sato Y, Hayashi T, Kato A, Aoyama H & Yoshikawa K
(2011) Histopathology 58, 835–846
Topographical, morphological and immunohistochemical characteristics of carcinoma in situ of the breast involving sclerosing adenosis. Two distinct topographical patterns and histological types of carcinoma in situ

A new method of margin evaluation in breast conservation surgery using an adjustable mould during fixation

A new method of margin evaluation in breast conservation surgery using an adjustable mould during fixation

Parathyroid hormone suppression by 22-oxacalcitriol in the severe parathyroid hyperplasia

The suppression of parathyroid hormone (PTH) secretion by the administration of 1,25-dihydroxyvitamin D [1,25(OH)2D3] and 22-oxacalcitriol (OCT) was evaluated in nude mice transplanted with human hyperplastic parathyroid tissue. The parathyroid tissue was obtained for transplantation from a patient with severe secondary hyperparathyroidism who had undergone a parathyroidectomy. Tissue specimens were transplanted into the gluteus muscle of female nude mice. Animals were divided into two groups; one group was fed a normal diet, and the other group was fed a low calcium diet during the administration of OCT and 1,25(OH)2D3. OCT and 1,25(OH)2D3 were intraperitoneally administered two times every week, for a total of eight times. Serum calcium and phosphate levels were significantly higher in the mouse administered 1,25(OH)2D3 than in the mouse administered OCT. Serum alkaline phosphatase activity was elevated similarly in the mouse administered either OCT or 1,25(OH)2D3. OCT strongly suppressed human PTH secretion from the graft in mice with normal serum calcium levels as did 1,25(OH)2D3. However, human PTH secretion from the graft was stimulated by the administration of a low-calcium diet, despite OCT and 1,25(OH)2D3 administration. In summary, OCT and 1,25(OH)2D3 suppress PTH secretion even from severe secondary hyperplastic parathyroid tissue only in mice with normal or high calcium serum levels.

Uniqueness of ductal carcinoma in situ of the breast concurrent with papilloma: implications from a detailed topographical and histopathological study of 50 cases treated by mastectomy and wide local excision

To clarify the diagnostic clues of ductal carcinomas in situ (DCIS) associated with papilloma and optimal clinical management of papilloma diagnosed on core needle biopsy (CNB).

Similarity estimation for reference image retrieval in mammograms using convolutional neural network

Periodic breast cancer screening with mammography is considered effective in decreasing breast cancer mortality. For screening programs to be successful, an intelligent image analytic system may support radiologists’ efficient image interpretation. In our previous studies, we have investigated image retrieval schemes for diagnostic references of breast lesions on mammograms and ultrasound images. Using a machine learning method, reliable similarity measures that agree with radiologists’ similarity were determined and relevant images could be retrieved. However, our previous method includes a feature extraction step, in which hand crafted features were determined based on manual outlines of the masses. Obtaining the manual outlines of masses is not practical in clinical practice and such data would be operator-dependent. In this study, we investigated a similarity estimation scheme using a convolutional neural network (CNN) to skip such procedure and to determine data-driven similarity scores. By using CNN as feature extractor, in which extracted features were employed in determination of similarity measures with a conventional 3-layered neural network, the determined similarity measures were correlated well with the subjective ratings and the precision of retrieving diagnostically relevant images was comparable with that of the conventional method using handcrafted features. By using CNN for determination of similarity measure directly, the result was also comparable. By optimizing the network parameters, results may be further improved. The proposed method has a potential usefulness in determination of similarity measure without precise lesion outlines for retrieval of similar mass images on mammograms.

Retrieval of reference images of breast masses on mammograms by similarity space modeling

Presentation of reference images that are similar to a query image can be helpful in medical image diagnosis and treatment planning. The purpose of this study is to investigate a method for retrieving relevant images of breast masses on mammograms as a diagnostic reference. In our previous studies, subjective similarities for pairs of masses were obtained from experienced radiologists and used as the gold standard for retrieving visually similar images. By use of multidimensional scaling, a subjective similarity space was spanned so that masses that were placed close to a query image can be retrieved as reference images. This method, however, required manual outlines of masses for image feature determination. In this study, we modelled this similarity space using convolutional neural network. The result was evaluated using the leave-one-out cross validation method in terms of the correlation between the subjective ratings and determined similarity measures. The relevance of retrieved images was also evaluated in terms of the precision, which is the fraction of pathology matched images in the retrieved images. The correlation coefficient between the subjective ratings and the determined similarity measure was moderate with 0.735, which was slightly lower than those of the previous methods. The average precision was high with 0.852 when the most similar image was retrieved, which was higher than those in the previous studies. The results indicate the potential usefulness of the proposed method in similar image retrieval of breast masses on mammograms.

Pseudo-micropapillary structures associated with columnar cell lesions of the breast are an artifact due to traumatic epithelial detachment: a potential pitfall which can lead to overtreatment

Dear Editor, Columnar cell lesions (CCLs) of the breast including flat epithelial atypia (FEA) are believed to be nonobligatory precursors of a low-nuclear-grade breast neoplasia family [1]. They are detected increasingly in needle core biopsies because of the presence of microcalcifications observed on screening mammography. Here, we report a hitherto undescribed artifact associated with CCLs of the breast, which superficially resembles micropapillary atypical ductal hyperplasia (ADH) or low-grade ductal carcinoma in situ (DCIS). The complexity of this artifact varies widely from a simple fold to a complex labyrinthine-like structure. If the latter is confused with genuine micropapillary structures or Roman bridges, overtreatment can occur because management of patients differs between pure CCLs and those associated with ADH/low-grade DCIS, especially when found in needle core biopsies. We have recently observed two cases of CCL of the breast that showed complex pseudo-micropapillary structures protruding into the duct lumen. Based on histopathological and immunohistochemical findings, we infer that these structures are not a true micropapillary overgrowth but an artifact, which originates from folding and adhesion of epithelial sheets detached from CCLs. The first case concerns a 49-year-old Japanese woman whose screening mammography revealed microcalcifications in the left breast. Vacuum-assisted needle core biopsy (VAB) was performed because the microcalcifications varied in size and shape and were localized to the upper half of the breast in a segmental fashion. The VAB was composed of 12 fragments of breast tissue. Four fragments contained CCLs; variably distended ductules were lined by columnar epithelial cells with apical cytoplasmic snouts (Fig. 1a–c). In the lumina of some dilated ductules, racetracks were seen or ribbon-like bridges continuous with the epithelial lining of CCL. These pseudo-micropapillary structures lacked fibrovascular cores and contained two epithelial layers. The cells were similar to luminal cells of CCL (Fig. 1c). Immunohistochemical staining with cytokeratin 5/6 demonstrated a few myoepithelial cells attached to the basal S. Ichihara (*) : S. Moritani :M. Hasegawa Department of Pathology, Nagoya Medical Center, 4-1-1 Sannomaru Naka-ku Nagoya, 460-0001 Aichi, Japan e-mail: shu-kkr@umin.ac.jp