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Summary We present a rare case of phosphoglyceride crystal deposition disease (PCDD), as a gynecologic disease, with reference to histogenesis of crystal deposition. An 84-year-old woman, who had undergone simple hysterectomy for uterine leiomyoma 44 years previously, presented with multiple masses in the bilateral adnexa and the pelvic wall. The bilateral adnexal tumors were resected. The masses histologically revealed a foreign-body granuloma composed of numerous tiny, radially arranged needle-like crystal lumps surrounded by multinucleated giant cells and macrophages. The crystals showed birefringence under polarized light and were positive for gold hydroxamic acid stain, and the tumor was thus diagnosed as PCDD. The masses revealed central cystic changes due to old hemorrhage, which contained crystal lumps without foreign-body reaction or birefringence. The present case demonstrated for the first time that phosphoglyceride crystals developed in old hemorrhagic foci, although it was not confirmed whether the old hemorrhagic foci were formed after hysterectomy or due to endometriosis.

Pilomatricoma usually contains a mutation in CTNNB1 that encodes β-catenin (BC). It also shows nuclear accumulation of BC protein, which plays an important role in tumorigenesis of pilomatricoma. In vitro studies have indicated that mutant BC protein is unphosphorylated and shows nuclear accumulation, but this theory has not been confirmed in various tumors with CTNNB1 mutation. We examined immunohistochemical localization of phosphorylated BC (pBC) and unphosphorylated BC (npBC) with regard to the modes of cell death or differentiation in 25 cases of pilomatricoma. As for the component showing shadow cell differentiation, BC was detected in cytoplasm/nucleus and along cell membrane in basaloid cells, whereas only in the latter in transitional cells in all cases. Meanwhile, npBC was localized along cell membrane of transitional cells, but not in basaloid cells, nor in nucleus of any components. The components with squamous differentiation also revealed the staining patterns similar to those seen in shadow cell differentiation in some cases. pBC was found in some cell fragments in the amorphous debris containing apoptotic bodies among shadow cell nests. These results suggested that npBC plays an important role in cell adhesion during differentiation and that pBC expression is associated with apoptosis of basaloid cells in pilomatricoma. BC accumulated in the nucleus was not immunoreactive for npBC possibly due to post-translational modification or conformational changes that resulted in loss of or masked antigenicity when BC is assumed to be unphosphorylated.

Endoscopic treatment for chronic subdural hematoma (CSDH) has been reported, but endoscopic findings of CSDH have not been thoroughly investigated. This study aimed to elucidate the relationship between endoscopic findings and CSDH recurrence. Furthermore, it examined the association between Nagahori’s histopathological staging of CSDH and outer membrane color. Here, we retrospectively analyzed the operative videos of 70 patients with CSDH. The endoscopic findings were investigated, and their correlations with CSDH recurrence, the reduction ratio of the midline shift, and hematoma thickness on day 30 after the operation were analyzed. The outer membrane was white in 21 cases, yellow in 25 cases, and red in 24 cases. CSDH recurred in three (4.2%) patients, all of whom had a white outer membrane (adjusted odds ratio, 18; 95% confidence interval, 1.6–20.6; P = 0.007). The other endoscopic findings were not significantly related to CSDH recurrence, extent of the reduction ratio of the midline shift, or hematoma thickness. The outer membrane colors of white, red, yellow, and white almost corresponded to the histopathological staging from type I to IV in order. Our findings suggest that a white outer membrane is a risk factor for recurrence; these colors may represent the extent of inflammation related to the evolution of CSDH estimated from the histopathological findings.

Background Recent preclinical data suggest that androgen receptor (AR) signaling plays a significant role in subsets of breast cancer. Clinical trials testing AR-targeting therapies in breast cancer have been conducted. Assessment of AR-signal in breast cancer tissue maybe useful for treatment selections. Prostate specific antigen (PSA) is the product of an androgen-responsive gene. Serum PSA (sPSA) can be detected in women by a highly sensitive assay although the concentration is much lower than that observed in males. We investigated if sPSA reflects tumor biology, including AR signaling in breast cancer patients. Methods In this study, 132 healthy controls and 144 breast cancer patients were enrolled. sPSA was evaluated by the chemiluminescent enzyme immunoassay (CLEIA) method. Correlations between sPSA and the various clinicopathological factors were analyzed. Results In post-menopausal state, sPSA detection rate was significantly higher in breast cancer patients compared with controls (27.4% vs 11.3%: p = 0.0090), but not in the whole cohort (29.2% vs 25.8%: p = 0.5265) or pre-menopausal subgroup (37.0% vs 42.6%: p = 0.6231). In post-menopausal breast cancer cases, higher sPSA value was associated with clinic-pathological factors including the expression of AR protein in primary legion. In a correlation analysis of quantitative data limited to post-menopausal metastatic breast cancer (MBC), sPSA was positively, albeit weakly correlated with clinic-pathological features including serum testosterone levels and AR positivity. Conclusions Our data suggest that sPSA may reflect tumor biological properties including AR activity in post-menopausal breast cancer.

A 57-year-old man visited our hospital for evaluation of an abnormal shadow identified on chest radiography. Chest computed tomography findings suggested diffuse bone metastases in the thoracic spine and the bilateral ribs. Notably, 18- fluoro-deoxyglucose positron emission tomography revealed no evidence of the primary tumor. Esophagogastroduodenoscopy revealed a small flat depressed lesion in the greater curvature of the gastric angle. Histopathological examination of this specimen revealed a signet-ring cell carcinoma. Histopathological examination of a biopsy obtained from the right iliac bone revealed a signet-ring cell carcinoma similar to that observed in the gastric mucosa. He was diagnosed with a gastric signetring cell carcinoma with multiple bone and bone marrow metastases. Cervical metastases caused gradual worsening of respiratory functions, necessitating artificial ventilation. He died of sudden ventricular tachycardia on the 36th day. Clinicians should be aware of the features of primary gastric cancer with bone and bone marrow metastases for early diagnosis and prompt treatment.

The relationship between methylation abnormality and autoimmune pancreatitis (AIP)-a representative IgG4-related disease-has not yet been elucidated. We identified SKI might have a significant methylation abnormality in AIP through methylation array analysis using the Illumina Infinium Human Methylation 450K BeadChip array, and investigated the relationship of SKI with AIP clinicopathological features. The methylation rate of SKI was assessed by quantitative SYBR green methylation-specific PCR, and the degree of SKI expression in tissue specimens was assessed by immunohistochemistry in 10 AIP cases, 14 cases of obstructive pancreatitis area in pancreatic ductal adenocarcinoma (PDA) without a history of AIP, and 9 normal pancreas (NP) cases. The SKI methylation ratio was significantly lower in AIP than in PDA and NP. Additionally, the immunohistochemical staining-index (SI) score for SKI was significantly higher in AIP than NP, although there was no significant difference between AIP and PDA. There was a strong negative correlation between SI score and SKI methylation ratio, and between the serum concentrations of IgG4 and the SKI methylation ratio. There was a moderate positive correlation between the serum concentrations of IgG4 and SI. SKI is thought to be an oncogene indicating that SKI hypomethylation and carcinogenesis might be linked to AIP. Furthermore, the correlation between serum concentrations of IgG4 and SKI methylation levels suggest SKI might be involved in the pathogenesis of AIP. However, the role of SKI has not been clearly elucidated. Further studies are needed to understand further the function of SKI.

An 83-year-old woman visited our hospital with a mass on her right breast mass. Breast ultrasonography revealed a tumorous lesion approximately 30mm in diameter in the right E region. Fibrous tumor was suspected from core needle biopsy. Since surgery for definite diagnosis was not desired, she was followed. Seven months after the first visit, skin redness, pain, and rapid increase in tumor size was consciously recognized, which prompted a reconsultation. The tumor diameter rapidly increased to 74 mm, and a total right mastectomy was performed as a semi-emergency procedure. Necrotic and hemorrhagic lesions were mixed in a mottled state in the cleaved surface of the excised specimen, and the pathological diagnosis was stromal sarcoma mainly comprising of fibrosarcoma components. Stromal sarcoma of the breast lacks the epithelial component of a malignant phyllodes tumor, and effective systemic therapy has not been established; therefore, cases with local recurrence or distant metastasis result in poor prognosis. Since we encountered a case of stromal sarcoma of the breast that showed a rapid increase after several months, we will provide a report with some literature consideration.

Additional file 1: Table S1. Preliminary experiment for selection of sPSA measurement kit (n = 10). Table S2. sPSA values in breast cancer patients and healthy controls. Table S3. sPSA values in post-menopausal breast cancer patients (n = 117). Table S4. Difference in sPSA values due to previous endocrine therapy (n = 58).

Mediastinal seminoma is an uncommon tumor that accounts for 25% of primary mediastinal germ cell tumors, which in turn comprise fewer than 5% of all germ cell tumors. Although CT normally shows a solid, lobulated tumor, mediastinal cystic seminoma has rarely been described. Here, we report a 24-year-old man who presented with a mediastinal cystic tumor that was resected after an 18-month delay via video-assisted thoracoscopic surgery while in the supine position; the procedure involved lifting the chest wall with a subcutaneous Kirschner wire. Pathological examination revealed a mediastinal cystic seminoma. No evidence of recurrence has been noted during 25 months of follow-up. Mediastinal cystic seminoma should be considered in the differential diagnosis of cystic lesions of the mediastinum. Moreover, video-assisted thoracoscopic resection may be an appropriate option for the diagnosis and treatment of such lesions.

Background Sebaceous carcinoma of the breast is a distinct variant of invasive ductal carcinoma. It is rare and only several cases have been reported. Case presentation An 80-year-old woman noted bloody discharge from her left nipple and palpated a lump in her left breast. Ultrasonography revealed a 19-mm mass in the left breast. Fine-needle aspiration suggested invasive ductal carcinoma. Partial mastectomy and sentinel lymph node biopsy were performed. On histological examination, the tumor revealed solid growth of small, round uniform cells with clear cytoplasm, partially intermingled with vacuolated cells indicative of sebaceous differentiation. The tumor cells contained abundant Sudan Black B-positive lipid droplets in the cytoplasm, and they were immunohistochemically positive for adipophilin. They were negative for estrogen receptor, progesterone receptor, and androgen receptor; positive for cytokeratin 7 and Ber-EP4; and partially positive for epithelial membrane antigen. Based on these findings, the patient was diagnosed with sebaceous carcinoma of the breast. Conclusions We diagnosed a rare case of sebaceous carcinoma of the breast.

A-70-year-old man with chordoma of the sacrum was treated with pazopanib (initially 400 mg/day, upto 800 mg/day). After 2 months of treatment, a significant tumor reduction was achieved and the patient was able to sit down easily. Therefore, the pazopanib therapy was continued. He had 14 months of progression-free survival.

Primary dedifferentiated liposarcoma originating in the mediastinum is extremely uncommon. Here, we report a case of mediastinal dedifferentiated liposarcoma. A 74-year-old man was admitted to our hospital with a left intrathoracic tumor ∼10 cm in diameter. Computed tomography that was taken in another hospital 2 years before the initial visit to our hospital had shown a lipomatous tumor ∼3 cm in diameter adjacent to the left lower pulmonary vein. The tumor was resected by left lateral thoracotomy with video-assisted thoracoscopic surgery. Pathological examination revealed primary mediastinal dedifferentiated liposarcoma. No evidence of recurrence has been seen as of 8 months postoperatively.

Keratinization is a kind of cell death called terminal differentiation and includes various patterns such as epidermal keratinization (EK), trichilemmal keratinization (TK), and shadow cell differentiation (SCD), whereas these have not been comparatively investigated from a standpoint of cell death. In the present study, surgically extirpated specimens of epidermal cyst, trichilemmal cyst, and pilomatricoma (10 cases in each) were subjected to immunohistochemistry for single-strand DNA (ssDNA), gamma-H2AX, cleaved caspase-3, cleaved lamin A, caspase-14, and CD138 to compare the modes of cell death and keratinization pattern. Transitional cells in pilomatricoma were immunoreactive, although not in whole part, for ssDNA and gamma-H2AX, and negative for cleaved caspase-3 and cleaved lamin A. Epidermal and trichilemmal cyst were negative for these 4 markers, except for ssDNA or cleaved lamin A in a small number of parakeratotic cells in a few cases. The keratinizing component showed caspase-14(+)/CD138(-) in epidermal cyst, caspase-14(-)/CD138(+) in trichilemmal cyst, and caspase-14(-)/CD138(-) in pilomatricoma. These results indicate that EK, TK, and SCD have a common property of apoptosis-like programmed cell death without caspase-3 activation or nuclear fragmentation. Meanwhile, they show different characteristics one another as follows: (A), DNA double-strand breaks occur in the transitional cells of SCD but not in EK/TK; and (B), EK, TK, and SCD can be distinguished by expression pattern of caspase-14 and CD138 in the keratinizing component.

Aims and background Hepatic tissues, including bile canaliculi and sinusoids, around primary or metastatic tumors are destructed and regenerate associated with tumor growth, and may show some phenotypic changes. The present study was undertaken to examine the expression of CD10 in bile canaliculi [CD10(BC)] and CD105 (endoglin) along hepatic sinusoids [CD105(HS)] in peritumoral hepatic tissue (PTH). Methods Fifty samples of resected liver bearing hepatocellular carcinoma (HCC) or metastatic carcinoma were immunostained for CD10 and CD105. The immunoreactivity for CD10(BC) and CD105(HS) in the background hepatic tissue of tumors and PTH was scored separately. Results CD10(BC) was moderately or markedly expressed in the background hepatic tissue without chronic hepatitis or cirrhosis in most of the cases, and was significantly downregulated in chronic hepatitis and cirrhosis. CD105(HS) was negative or minimally positive in most of the cases of hepatic tissue bearing metastatic carcinoma, and showed a significant increase in chronic hepatitis and cirrhosis. Compared with the background, PTH revealed significantly decreased CD10(BC) staining irrespective of HCC or metastatic carcinoma, and showed belt-like CD105(HS) expression in 66.7% of the cases of metastatic carcinoma and in 88.6% of those with HCC. Conclusions These data indicate that the expression patterns of CD10(BC) and CD105(HS) in PTH are similar to those in chronic hepatitis and cirrhosis, which may be caused by persistent injury and resultant regeneration of hepatic tissue.

A peculiar case of astrocytoma showing a histological appearance similar to granular cell tumor was reported. The tumor consisted of large round cells containing numerous intracytoplasmic eosinophilic granules, partially intermingled with atypical astrocytes, and part of it showed a transition to distinct areas of fibrillary astrocytoma. The granules were periodic acid-Schiff-positive (with resistance to diastase digestion), negative for fat stains and revealed lectin-binding patterns similar to those in granular cell tumor. Ultrastructurally the granules were partially membrane-bound, dense bodies compatible with secondary lysosomes. It was suggested that the granular cells were of astrocytic origin because of their immuno reactivity for glial fibrillary acidic protein (GFAP) and ultrastructural observation of intermediate filaments corresponding to GFAP. Acta Pathol Jpn 40: 206-211, 1990.

We investigated the modes of participation of macrophages in the formation of non-specific (i.e., unrelated to membranous lipodystrophy) membranocystic lesions (MCLs). Surgical specimens of atherosclerosis and chronic panniculitis containing MCLs as well as experimentally formed MCLs were examined, using paraffin sections, by Sudan black B (SBB) stain and by immunostaining for CD68, Bax protein and advanced glycation end products (AGEs). In the atherosclerotic lesions, MCLs were formed by a gradual fusion of SBB-positive multivesicular structures in the macrophages, associated with the cell breakdown. MCLs in the panniculitis were formed in the macrophages, as in atherosclerosis, or derived from degenerative fat cells, often with attachment of macrophages. CD68 was demonstrated in some MCLs or around them, and Bax was also present in some MCLs as well as some macrophages in both lesions. On the other hand, macrophages were not involved in the experimental MCLs. AGEs were widely detected in some MCLs, macrophages and degenerative background in all specimens. These results suggest that MCLs share AGEs as common components with various types of fat degeneration, and are formed physicochemically in the event that macrophages cannot dispose of the degenerative fat sufficiently due to their relative functional impairment and/or the physical circumstances.

Background: Pyogenic granuloma (PG) has been regarded as a florid expression of granulation tissue (GT) proliferation and shows distinct biological behavior compared to conventional GT. PG has not been examined from a standpoint of apoptosis. Methods: PG (15 cases), GT (14 cases) and capillary hemangioma (CH, 8 cases) were compared using in situ 3′-tailing reaction (ISTR), a histochemical method for identifying apoptotic cells, and immunohistochemistry for Ki-67, Bcl-2 and Bax proteins, in order to clarify and involvement of apoptosis in the difference of biological characteristics between PG and GT. Results: PG showed significantly lower ISTR-labeling indices than GT and CH and more frequent Bcl-2/Bax expression than GT, whereas Ki-67-labeling indices were variable from case to case and did not show any significant differences among any groups. Conclusions: It is consequently suggested that the low apoptotic rate in PG is closely related to its characteristic rapid growth and is regulated by Bcl-2 family proteins.

The modes of cell death in pilomatricoma were analysed using 27 nodules. The shadow cells with lost nuclei and preserved cytoplasms were morphologically considered to be derived from basaloid cells via transitional cells, which showed gradual loss of nucleic acid by Feulgen reaction and methylgreen-pyronin stain and no nuclear fragmentation. This process was regarded as cell death associated with terminal differentiation into hair. Amorphous debris among the shadow cells contained many fragmented nuclei (apoptotic bodies), which were directly derived from basaloid cell layer focally undergoing apoptosis and did not have any transition to transitional cells. Although in situ 3'-tailing reaction for a detection of dying cells labelled both transitional cells and apoptotic bodies in the amorphous debris, these two components were considered to be on different histogenetic pathways. Immunostainings for the Bcl-2 family revealed no expression of Bax, Bad or Bak protein in any components, whereas Bcl-2 protein was detected in the periphery of basaloid cell layer, but not in the transitional or shadow cells. These results indicate that there are two different modes of cell death in pilomatricoma: i) terminal differentiation into shadow cells; and ii) conventional apoptosis observed as amorphous debris.

We experienced simultaneous coronary artery bypass grafting and cardiac pheochromocytoma resection under cardiopulmonary bypass in a 79-year-old woman with atherosclerotic angina. During manipulation of the tumor under cardiopulmonary bypass, the serum norepinephrine concentration increased to over seventy times the normal limit, and there was a 25-mmHg rise in mean arterial pressure. Cardiopulmonary bypass has been recommended for the resection of cardiac pheochromocytoma to isolate the heart from the systemic circulation, and thus prevent massive catecholamine release when handling the tumor. However, the serum catecholamine concentration surged in our patient during tumor manipulation under cardiopulmonary bypass, probably because of the reperfused blood from the operating field. We suggest that cardiopulmonary bypass be performed for the anesthetic management of cardiac pheochromocytoma resection, because excessive hypertension can be avoided during cardiopulmonary bypass, even if the catecholamine concentration increases excessively when handling the tumor.

Background: Atypical parathyroid adenoma is a borderline neoplasm defined by histological findings, while its cytological characteristics have not been described so far.Case: A 43-year-old man was diagnosed as primary hyperparathyroidism due to parathyroid tumor by medical check-up as a momentum. Although the extirpated tumor was welldemarcated by fibrous capsule, a few small tumor nests were observed in the capsule, which fulfilled the histological diagnostic criteria of atypical adenoma. Some of the tumor cells had giant and/or hyperchromatic nuclei, with intranuclear cytoplasmic inclusions in part, which may be used in favor of an estimation of adenoma rather than carcinoma. In addition, there were few mitotic figures in the tumor tissue and Ki-67 labeling index was as low as that in the conventional parathyroid adenomas.Conclusion: It is suggested that the present case is biologically akin to the conventional adenoma and that nuclear atypy and low proliferative activity are useful findings to estimate parathyroid neoplasms to be benign in the cytological specimens.

An 11-year-old Japanese girl noticed a small nodule, with mild tenderness, on the right index finger 5 years before visiting our outpatient clinic. She had no familial history of neurofibromatosis or past history of traumatic injury at the site of the tumor. Physical examination revealed a slightly elevated, subcutaneous, nodular tumor in the volar aspect between the proximal and distal interphalangeal joints of the digit (Fig. 1A). By magnetic resonance imaging examination, the tumor showed low density on both T1- and T2-weighted images, and was located just adjacent to the tendon with no invasive signs. The tumor was extirpated; at operation, it was well circumscribed and mobile without adhesion to adjacent tendon or nerve, and was easily removed. Grossly, the tumor was a well-circumscribed, firm nodule (10 mm x 8 mm x 5 mm in size) (Fig. 1B). The cut surface was whitish, homogeneous, and solid without cystic lesions. Histologically, it was an unencapsulated, paucicellular dense, fibrous nodule with a concentric circular arrangement of collagen bundles (Fig. 2A). Amongst the fibrous bundles, a small number of ovoid/epithelioid or plump spindle cells were arranged in a corded, trabecular, or whorled (onion bulb-like) pattern (Fig. 2B); a storiform pattern was not noted. These cells were relatively uniform and had a somewhat elongated, slightly hyperchromatic nucleus with fine granular chromatin. Neither nuclear pleomorphism nor multinucleated cells were evident, and necrosis and mitotic figures were not observed. Periodic acid-Schiff (PAS) stain after diastase digestion highlighted the corded or whorled pattern of the tumor cells by encasing them. For immunohistochemical examination, formalin-fixed, paraffin-embedded serial tissue sections were stained by a labeled streptavidin-biotin method. The tumor cells were positive for vimentin and epithelial membrane antigen (EMA) (Fig. 3A), and negative for pan-cytokeratin, carcinoembryonic antigen (CEA), CD34, alpha-smooth muscle actin, desmin, and CD68. Type IV collagen and laminin (Fig. 3B) were detected along the cords or whorls of the tumor cells, similar to the staining pattern of the diastase-PAS reaction. Schwann cells and axonal components, immunoreactive for S100 protein and neurofilament, respectively, were focally detected just adjacent to the cords or whorls, although the tumor cells per se did not express these proteins. Consequently, the tumor was found to be perineurial in origin and was diagnosed as cutaneous sclerosing perineurioma.

Expression of bcl-2 oncoprotein (Bcl-2) in carcinomas and their precursor lesions in the colon, stomach, uterine cervix (squamous and glandular epithelium), and endometrium was examined immunohistochemically using clone 124 monoclonal antibody. Most cases of premalignant lesions in the colon (adenoma, 80.6%), stomach (metaplastic gastritis, 77.1%, mainly positive in the proliferative zone), endocervix (glandular dysplasia, 87.5%) and endometrium (endometrial hyperplasia, 65.4%) showed intense immunoreactivity for Bcl-2, whereas fewer than 30% of adenocarcinomas in these tissues had no or weak Bcl-2 expression. In the stomach, adenomas with definite Bcl-2 expression were 37.5% of the cases examined. Conversely, most of both squamous intraepithelial neoplasia and squamous cell carcinoma of the uterine cervix showed weak or no Bcl-2 expression. These results suggest that upregulation of Bcl-2 in premalignant lesions and downregulation after malignant change is, to some extent, a common event in the glandular system, but not in the squamous epithelium of the uterine cervix. Bcl-2 may play an important role in keeping the transformed cells alive at the early stage of multistep carcinogenesis in the glandular tissue by an escape from a regulatory mechanism of apoptosis for further accumulation of gene abnormalities.

Colorectal polyps were analyzed from the standpoint of cell death by using the in situ 3'-tailing reaction (ISTR), which identifies cell death-associated DNA double strand breaks, and immunohistochemistry for bcl-2 oncoprotein (BCL-2) and for Ki-67. There were few ISTR-positive cells in the non-neoplastic glands, whereas 38% of non-neoplastic mucosa just adjacent to the adenoma had many labeled nuclei, suggestive of cell death associated with replacement by tumor. The neoplastic glands contained variable number of ISTR-positive nuclei, mostly showing the morphological feature of apoptotic bodies. In the representative glands with the most prominent ISTR-labeling, their indices did not have a significant relationship to the grade of atypia, to the proliferative activity (Ki-67 labeling indices) of neoplastic glands, or to BCL-2 stainability. In each case, however, the neoplastic glands with no or few ISTR-labeled nuclei tended to express BCL-2 intensely, and all lesions of adenoma or carcinoma with more than 15% of ISTR-labeling indices showed weak BCL-2 immunoreactivity. In general, BCL-2 expression was significantly stronger in the adenoma than in non-neoplastic mucosa and carcinoma, although there was no significant difference of ISTR-labeling between adenoma and carcinoma. These results indicate that cell death in colorectal neoplastic polyps does not have a significant influence on their growth rate, and that BCL-2 plays some role, at least in part, in the regulation of apoptosis.

症例は62歳女性.1987年より高血圧にて当科通院中,肝機能障害および抗ミトコンドリア抗体陽性のため,1989年9月に肝生検施行.慢性非化膿性破壊性胆管炎を認めScheuer分類2期の無症候性原発性胆汁性肝硬変(PBC)と診断した.1990年11月,腰椎の圧迫骨折,尿中BJ蛋白(κ型)を認め,骨髄像にて異型性のあるplasma cellを63.4%認めたため,BJ-κ型多発性骨髄腫(MM)と診断.2疾患の合併はまれで,文献上5例報告されているにすぎない.本例はPBCとBJ-κ型MMの合併,PBC合併のMMに対しインターフェロン(IFN)療法を行った点では最初の報告である.MMはIFN療法により良好なコントロールがえられ4年以上にわたってこの病態の推移を観察しえたので,両者の合併のメカニズム,IFN療法の影響などを考案する上で貴重な症例と考え報告した.

A peculiar case of bladder carcinoma showing shadow cell differentiation (SCD) in a 72-year-old man is presented. The tumor histologically revealed high grade urothelial carcinoma (UC) and partially contained squamous component with a transition to shadow cell nests, similar to those seen in cutaneous pilomatricoma (PMX). Immunohistochemically, the modes of cell death in the component of SCD were identical to those in PMX. The present case as well as 10 cases of cutaneous PMX showed nuclear expression of beta-catenin, whereas 10 cases of bladder UC with squamous differentiation revealed membranous localization without nuclear expression. These results suggest that nuclear accumulation of beta-catenin may play an important role for SCD in the present case. SCD in extracutaneous tumor is extremely rare and, in the literature, the present case is the second one as for bladder carcinoma.

Pleomorphic carcinoma is a rare malignancy of the lung. Here we present a 68-year-old man who was admitted to our hospital for examination of an abnormal radiogram of the chest. The radiogram revealed a large mass in the right lung field. A chest computed tomographic (CT) scan demonstrated a nonsegmentalmass like consolidation. Percutaneous CT-guided fine-needle needle biopsy from the lung was performed, and the specimen demonstrated pulmonary pleomorphic carcinoma. The patient was initially treated with two courses of cisplatin (CDDP) and docetaxel (DOC), and still showed progressive disease (PD). Therefore, we administered S-1 following radiotherapy. The chest CT revealed partial response after 4 months. We experienced a pulmonary pleomorphic carcinoma which showed a response to salvage chemotherapy with S-1.

A 33-year-old woman had hematochezia for 5 months. A total colonoscopy showed an easily-bleeding elevated lesion with a nodular lesion in the lower rectum. Histological findings of a conventional biopsy from the lesion showed MALT (mucosa-associated lymphoid tissue) lymphoma and she was diagnosed as stage I. The monoclonality of B-cells was not detected by polymerase chain reaction products for immunoglobulin heavy chain. We selected antibiotic therapy because Helicobacter pylori was detected in culture of the patient's gastric biopsy specimens. The antibiotic therapy was successful, but her symptoms worsened. We therefore gave her with 30 Gy radiation therapy. She recovered a month after the radiation. Histological complete remission was confirmed 4 months after the radiation. Adverse events of the radiation therapy included anal pain for 1 month and premature ovarian failure. Radiation therapy may be useful for localized rectal MALT lymphoma.

DNA strand breaks (nicks) in non-parenchymal cells (NPCs) in CCl4-induced acute or chronic liver injury in rats were detected using an in situ nick translation method; their dynamic changes were analysed in relation to the proliferation pattern of hepatocytes and NPCs, as revealed by bromodeoxyuridine (BrdU)-up-take. In acute injury, hepatocyte proliferation started before centrilobular necrosis had occurred, whereas BrdU-labeled sinusoidal NPCs markedly increased only after centrilobular necrosis was apparent. DNA breakages in NPCs paralleled the proliferation pattern of these cells, suggesting that nicks are physiological, and reflect proliferation and activated gene expression. In chronic injury, liver cirrhosis developed after 9 weeks, but BrdU-labeling of hepatocytes was almost the same level as that in untreated liver. The number of BrdU-labeled NPCs showed only a slight increase, while those with DNA breakages were much more frequent in the cirrhotic stage, suggesting a significant role for NPCs in the fibrotic process. These results indicate that DNA strand breaks in NPCs act as a marker for activation states such as proliferation, differentiation and/or activated gene expression.

Liver biopsy specimens of 65 cases of chronic viral hepatitis, including 29 cases of type B, 34 cases of type C, and two cases of non-A, non-B, non-C type, were immunohistochemically stained for proliferating cell nuclear antigen (PCNA) to evaluate the proliferative acivity of hepatocytes. According to a histopathologic evaluation using the histology activity index (HAI) scoring system, chronic persistent hepatitis and chronic active hepatitis were clearly differentiated with no overlapping of the score. The labeling indices of PCNA of hepatocytes in chronic persistent hepatitis had a significant relationship with HAI scores ( r = .54), suggestive of a contribution of lobular hepatocyte necrosis and/or portal inflammation to the regenerative rate of hepatocytes, but did not exceed 3.0%. On the other hand, 11 of 47 cases of chronic active hepatitis showed PCNA labeling indices higher than 3.5% without any significant relationship with the HAI scores. There was no significant difference, however, of distribution of HAI scores or PCNA labeling indices between hepatitis types B and C. Based on current concepts of the role of hepatocyte proliferation in the development of liver cirrhosis and hepatocellular carcinoma, the present results suggest that the high proliferative rate of hepatocytes subject to the persistent liver cell injury in chronic active hepatitis may be related to a reconstruction pattern of the liver in cases of progression to cirrhosis and development of hepatocellular carcinoma.

最近増加している弱毒腐生菌による深在性真菌症のうち, トリコスポロン症に注目して症例の検討・文献的および実験的検討を行い, 以下の結果を得た.1) トリコスポロンの組織内形態はカンジダに類似するが, 仮性菌糸・真性菌糸の両者が混在して存在し, 菌糸の太さが不規則で, 三日月形の胞子や四角形の分節胞子がみられるなど多彩な形態を示した. また免疫組織化学的にもカンジダとの鑑別が可能であった. 2) 文献的には1991年までに85例の深在性トリコスポロン症の報告があり, 67例が播種性または敗血症性であった. 55例が白血病などの血液疾患を有するcompromised hostsに発症し, 定型例では無反応性病変や壊死性病変が多いが, 生存例では何らかの組織反応が少なくとも一部に存在していた. 3) トリコスポロンの感染実験では, 無処置マウスに菌を静注すると肺に限局した化膿性肉芽腫が形成され, 菌は2日以内に処理された. これに対し, 抗癌剤投与により白血球減少をおこしたマウスでは全身諸臓器に菌糸の発育を伴う無反応性病変を形成したが, 白血球の回復と共に組織反応がおこり, 菌はすみやかに処理された. 以上の結果は定型的な日和見感染の所見で, 生体防御機能の破綻が発症に重要と考えられたが, カンジダ・アスペルギルス・ムーコルなどの感染実験と比較すると, トリコスポロンはこれらの菌よりも病原性は弱いものと思われた.

A78-year-old female was admitted to our hospital with anorexia due to ascites. We were not able to diagnose by cytological diagnosis. For a definite diagnosis she underwent an open biopsy. Histological findings revealed observable papillary adenocarcinoma with psammoma body, carcinoma cells were positive for Ber-EP4 on immunostaining, and ovaries were normal. Thus, we made a diagnosis of peritoneal serous papillary adenocarcinoma. She was treated by intraperitoneal administration of CDDP(20 mg/day: day 1, every four weeks). Ascites vanished and CA125 was within the normal range. There was no recurrence after 3 years, but Virchow's lymph node metastasis occurred. The patient is still alive 12 months after metastasis with CDDP intraperitoneal administration.

Increasing evidence shows the existence of nonproliferation-specific gene(s) whose expression is mostly present in growth-arrested cells. One member of this gene family has been identified by previous work as a nuclear protein of 57,000 Da, termed statin. Logical extensions of statin research are to identify the genomic and cDNA clones encoding for statin and to study the regulation of statin gene expression. During the search for the statin gene, we have identified a cDNA clone and a genomic clone named S1 and S10, respectively, by screening a rat brain lambda gt11 expression library with the statin antibody and subsequently using S1 cDNA as a probe to screen a rat genomic cosmid library. Here, we report the cloning and sequencing of the S1 cDNA and S10 genomic clones. Primary sequence analyses indicate that the derived amino acid sequence of S1 shares high homology (greater than 92.6%) with human elongation factor 1 alpha (EF-1 alpha), whereas the 5'- and 3'-untranslated regions are less than 20% homologous. Despite the unusually high degree of similarity between S1 and human EF-1 alpha at the amino acid sequence level, their protein products are different and immunologically distinct. The in vitro transcription and translation product of S1 (pS1), a 49,000-Da polypeptide, reacts only with the monoclonal antibody against statin; this antibody exhibits no antigenic reaction to the EF-1 alpha protein. Northern blot analysis shows that the S1 message is most abundant in G0 phase of 3T3 mouse fibroblasts, but becomes significantly reduced in G1 and S phase cells. EF-1 alpha messages do not show such dramatic changes during cell cycle phase transition. These findings suggest that the expression of the identified S1 cDNA clone is specific for nonproliferating cells and that the in vitro translation product of the S1 cDNA is recognized by the statin antibody. Genomic Southern blots indicate that S1 cDNA is encoded by a single copy gene in the rat genome and is a unique member of the EF-1 alpha/S1 supermultigene family. DNA sequence analysis demonstrates that the rat S1 transcription unit is 12 kilobase pairs in length and contains seven introns. The organization of exons is virtually identical between S1 and human EF-1 alpha. In contrast, neither a TATA box nor a CAAT box is located in the proximal 5'-flanking regions from positions -1 to -1359 of the S1 gene, where we could expect to find the regulatory region containing the elements controlling gene expression; no evident sequence homology to the human EF-1 alpha gene is detected in this region.(ABSTRACT TRUNCATED AT 400 WORDS)

We report a rare case in which mucous glands, similar to pyloric or Brunner's glands, developed in the residual jejunum (46 cm in length) long after wide resection of the small intestine. The mucous glands were observed in the mucosal and submucosal layers near the duodenum, and the mucin showed a positive reaction by paradoxical concanavalin A staining and immunoreactivity for HIK-1083, which were histochemically the same as those in the pyloric/Brunner's glands. This type of metaplasia in the small intestine without ulceration has not been described in the literature so far. It was speculated that these glands developed as a defense response or adaptation against relatively excessive acid due to the short small intestine.

A-46-year-old male with advanced-stage IV multicentric gastric cancer was treated with S-1/CDDP as neoadjuvant chemotherapy. S-1 (initially 100 mg/day, up to 120 mg/day) was orally administered for 3 weeks (day 1-21) followed by 1 drug-free week as a course, and CDDP (initially 60 mg/day, up to 100 mg/day) was administered by intravenous drip on day 8. After the fourth course, a significant tumor reduction was obtained and curative surgery was performed. Thereafter, S-1 therapy was continued. There has not been any recurrence for 19 months postoperatively.