[A Case of a Malignant Phyllodes Tumor of the Breast with Osteogenic Sarcoma Which Repeated Local Recurrence].

The patient is a 39-year-old woman. At the age of 34, she recognized a 22 mm sized mass in the upper outer quadrant of her right breast, which was diagnosed as a fibroadenoma. 5 years later, the mass increased to 45 mm. We performed lumpectomy which led to a diagnosis of a malignant phyllodes tumor with osteogenic sarcoma. Since the resection margins were positive, we performed mastectomy in addition. Nine months after surgery, a 23 mm large mass appeared on the right fifth costal. Recurrence of malignant phyllodes was suspicious from cytological diagnosis and since thoracoabdominal CT showed no metastasis to other organs, we performed resection. Histological results were the same as the primary tumor. Two months more later, an 11 mm large mass revealed in the right anterior thoracic region. We performed resection again, which showed the same histological features as the primary tumor. Since malignant phyllodes tumors often recur in the early postoperative period, a close follow-up is recommended.

[A Case of Transverse Colon Cancer with Metastatic Recurrence in Bilateral Inguinal Lymph Nodes].

A woman in the 60s. She was referred to our hospital because the fecal occult blood test was positive. Colonoscopy was performed. Cancer is found in the transverse colon. There were no metastases in the lungs and liver. Laparoscopic left hemicolectomy was performed. Histopathological examination was adenocarcinoma(tub1>tub2>muc), pT1b, pN2, ly2, v1, pPM0, pDM0, pRM0, budding(0, Grade 1), fStage Ⅲb. After postoperative adjuvant chemotherapy, she visited an outpatient clinic 8 months after surgery with a complaint of swelling of both inguinal lymph nodes. The swollen inguinal lymph node was relatively soft and there was no evidence of infection. A biopsy of the bilateral lymph nodes was performed. Histopathological examination revealed adenocarcinoma containing mucus components. These findings were consistent with histological findings in transverse colon cancer. Based on these results, we diagnosed metastatic recurrence from transverse colon cancer to both inguinal lymph nodes.

[Resection of a Desmoid Tumor Originated from Greater Omentum with No History of Open Surgery].

Here we report a case of a 41-year-old male patient who underwent resection of a desmoid tumor originating from the greater omentum with no history of open surgery. An elastic hard mass was palpated in the left upper abdomen, but there were no abnormalities on serum chemical tests, including tumor markers. Computed tomography showed a parenchymal tumor located near the descending colon. Integrated positron-emission tomography and computed tomography revealed moderate accumulation of tracer in the tumor. An intra-abdominal malignant mesenchymoma was suspected and surgery was performed. The tumor was located in the anterior portion of the greater omentum. It partially invaded the diaphragm, and the affected regions were concurrently resected. The resected specimen measured 80 mm at longest diameter. The cut surface was grayish white and parenchymal. The histopathological findings showed the atypical spindle shaped tumor cells grown with collagen fiber progression. Immunohistochemical staining for ß-catenin showed strong staining in the nuclei and cytoplasm of tumor cells. The patient was diagnosed with desmoid tumor originating from the greater omentum. The desmoid tumor with no history of open surgery was rare. We report this rare case, along with a discussion of the literature.

Transforming growth factor ß- and interleukin 13-producing mast cells are associated with fibrosis in bone marrow.

Although bone marrow fibrosis is a lethal condition, its underlying mechanism is not fully understood. This study aimed to investigate the pathogenesis of fibrosis in the bone marrow through histologic examination of mast cell infiltration and the expression of fibrosis-associated cytokines. We analyzed 22 bone marrows with fibrosis (8 primary myelofibrosis [PMF], 5 post-essential thrombocythemia [ET], myelofibrosis, and 9 myelodysplastic syndrome [MDS] with bone marrow fibrosis [BMF]). Immunohistochemical and immunofluorescence stainings were performed using anti-mast cell tryptase, interleukin (IL) 13, transforming growth factor ß (TGF-ß), CD34, and CD42b antibodies. The number of mast cells in bone marrows with fibrosis was significantly higher than that in controls (P<.0001 for all cases with fibrosis versus control, P=.0470 for PMF versus control, P<.0001 post-ET myelofibrosis versus control, and P=.0005 for MDS with BMF versus control). Moreover, bone marrows with higher fibrotic grades exhibited greater amounts of infiltrating mast cells. Mast cells were positive for TGF-ß and IL-13 in bone marrows with fibrosis of all 3 groups. Megakaryocytes were negative for TGF-ß in post-ET and MDS with BMF, but some megakaryocytes in PMF were weakly positive for TGF-ß. Megakaryocytes were negative for IL-13 in all 3 groups. Blasts were negative for both TGF-ß and IL-13 in all 3 groups. Thus, TGF-ß- and IL-13-producing mast cells might be key players in the development of BMF. Therefore, mast cells could be potential therapeutic targets for the treatment of BMF.

Infiltration of effector regulatory T cells predicts poor prognosis of diffuse large B-cell lymphoma, not otherwise specified.

Regulatory T cells (Tregs) specifically express the transcription factor forkhead box P3 (FOXP3) and contribute to tumor progression. FOXP3-positive cells have been recently proven to be heterogeneous in phenotype and function, including effector Tregs (eTregs), naïve Tregs, and non-Tregs, which harbor no suppressive function. Therefore, it is crucial to investigate the "true Treg (eTreg)" population, rather than the entire FOXP3 population, with regards to their effect on tumor immunity. In particular, in diffuse large B-cell lymphoma, not otherwise specified (DLBCL, NOS), FOXP3-positive cells correlated with a better prognosis. The present study sought to evaluate the relationship between the prognosis of DLBCL, NOS patients and the infiltration of true Tregs by employing dual immunostaining with FOXP3 and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4). CTLA-4 is a negative immunomodulatory known to be expressed by eTregs, but not by non-Tregs. Lymph nodes from 82 nodal DLBCL, NOS patients were stained with anti-FOXP3 and anti-CTLA-4 antibodies. A high infiltration of FOXP3-positive cells was associated with a significantly better prognosis than patients with low levels of FOXP3-positive cells for overall survival (OS) (P = .0233). In sharp contrast, a high infiltration of FOXP3/CTLA-4 double-positive cells was significantly associated with a poor prognosis than patients with low levels of FOXP3/CTLA-4 double-positive cells for OS (P = .0121) and progression-free survival (P = .0171), independent of the international prognostic index. FOXP3/CTLA-4 double-positive cells, eTregs, play an important role in DLBCL, NOS progression.

[A Case of Inflammatory Breast Cancer with Very Severe Obesity].

A 39-year-old woman with very sever obesity was admitted to our hospital for a right breast redness and hardness. Her height, weight and BMI were 166 cm, 145 kg and 52.6 kg/m2. Her breast had peau d'orange. CT scan showed swelling of whole right breast and Level I , II lymph node. We performed core needle biopsy and diagnosed as the inflammatory breast cancer with ER and HER2 positive. We introduced chemotherapy(pertuzumab, trastuzumab and paclitaxel)and nutrition counseling in order to reduce her body weight. After 4 courses of chemotherapy, the clinical complete response was obtained and her body weight decreased to 125 kg. We performed mastectomy and axillary node resection and confirmed pathological complete response. Adjuvant chemotherapy(5-FU, epirubicin and cyclophosphamide), adjuvant trastuzumab therapy, postmastectomy radiation therapy and adjuvant hormonal therapy were administered. There have been no signs of recurrence as of 2 years after the operation.

Role of mast cells in fibrosis of classical Hodgkin lymphoma.

The underlying mechanism of fibrosis in classical Hodgkin lymphoma (CHL) remains uncertain. This study aimed to investigate the association of fibrosis in the lymph nodes of patients with CHL through histological examination of the expression of cytokines associated with fibrosis and mast cell proliferation. Additionally, we sought to determine the degree of mast cell infiltration in a nodular sclerosis subtype of CHL (NSCHL) compared with that in non-NSCHL. We analyzed lymph nodes from 22 patients with CHL, of which eight were of the NSCHL and 14 of the non-NSCHL subtype, using immunohistochemical staining of forkhead box P3 (FOXP3), transforming growth factor (TGF)-ß, interleukin (IL)-3, IL-13, and stem cell factor (SCF). Mast cells were positive for TGF-ß and IL-13, and FOXP3-positive cells were negative for TGF-ß. Only the expression of IL-13 in Hodgkin and Reed-Sternberg (HRS) cells was significantly more frequently observed in NSCHL than that in non-NSCHL (P = 0.0028) and was associated with a higher rate of fibrosis (P = 0.0097). The number of mast cells was significantly higher in NSCHL than that in non-NSCHL (P = 0.0001). A significantly positive correlation was observed between the rate of fibrosis and the number of mast cells (correlation coefficient, 0.8524; 95% CI, 0.6725-0.9372) (P <0.0001). The number of mast cells was significantly higher in the group with IL-13-positive HRS cells than that in the group with IL-13-negative HRS cells (P = 0.0157). Based on these findings, we hypothesize that IL-13 production by HRS cells may lead to fibrosis, and furthermore, promote mast cell proliferation and infiltration. This in turn might further produce the fibrotic cytokines IL-13 and TGF-ß, resulting in fibrosis typical of NSCHL.

Central regions of keloids are severely ischaemic.

We classified scars as keloids, hypertrophic scars and mature scars, and then examined the scars for differences in central and marginal vascularization. We found significant differences in localized hypoxia-induced factor-1α (HIF-1α) expression and vascular density in keloids, but no localized differences in hypertrophic or mature scars. The central areas of keloids exhibited higher HIF-1α expression and lower vascular density than marginal areas, suggesting that the former are severely ischaemic.

Dermatopathic Lymphadenopathy With Increased IgG4-Positive Plasma Cells.

Both dermatopathic lymphadenopathy (DL) and immunoglobulin G4-related disease (IgG4-RD) are frequently complicated with allergic diseases. However, the relationship between DL and IgG4-RD is not well known. To clarify this relationship on the basis of clinical and pathological findings, including IgG4-positive (IgG4+) plasma cell infiltration in lymph nodes (LNs) of DL patients, we analyzed LNs of 11 DL patients using immunostaining of IgG, IgG4, forkhead box P3 (FOXP3), transforming growth factor (TGF)-ß, interferon (IFN)-γ, and matrix metalloproteinase (MMP)-1, MMP-8, and MMP-13. Toluidine blue staining was also performed to identify mast cells. Of 3 patients with a high ratio of IgG4+/IgG+ cells (>40%) and elevated serum IgG4 levels, 2 developed IgG4-RD, whereas the other patient did not. Of 8 patients with a low ratio of IgG4+/IgG+ cells (<40%) or no infiltration of IgG4+ cells, 5 who could be followed did not develop IgG4-RD. The numbers of mast cells were similar to those of TGF-ß-positive cells, and serial sections showed that mast cells possibly produce TGF-ß. LNs of DL patients with a high ratio of IgG4+/IgG+ cells had significantly more mast cells and TGF-ß-positive cells than those of patients with a low ratio of IgG4+/IgG+ cells or no infiltration of IgG4+ cells. However, no fibrosis was observed in LNs of both groups. IFN-γ was positive in interdigitating dendritic cells, Langerhans cells, and macrophages. MMP-1, MMP-8, or MMP-13 was expressed in macrophages. The lack of fibrosis in LNs may have been due to the production of IFN-γ, MMP-1, MMP-8, or MMP-13. Thus, DL with increased IgG4+ cells seems to be a phenotype of IgG4-RD in LNs.

Assessing the histological type and grade of primary parotid carcinoma by fine-needle aspiration and frozen section.

OBJECTIVE: The aim of this study is to compare preoperative fine needle aspiration cytology (FNAC) and intraoperative frozen section (FS) for the correct identification of malignancy, histological grade, and histological type. METHODS: FNAC was performed on all 105 patients and FS on 71 patients with parotid carcinoma. RESULTS: The rate of correctly determining the histological grade by FNAC and FS was 32% and 73%, respectively. The correct diagnosis rate for both the histological type and grade by FNAC and FS was 20% and 48%, respectively. CONCLUSIONS: The correct grading of both high and low/intermediate grade carcinoma is possible in 70-80% of patients by FS. If the histological grade is identified correctly, the extent of resection can usually be decided appropriately. Therefore, we should put emphasis on determining the histological grade.

Takayasu arteritis and ulcerative cutaneous sarcoidosis.

A 67-year-old woman was referred to our hospital due to a refractory lower extremity ulcer. Occlusion of the bilateral superficial femoral arteries and a difference (>50 mmHg) in blood pressure between the bilateral upper limbs were noted. In addition to occlusion of the left subclavian artery and stenosis at the ostium of the right coronary artery, these findings led to a diagnosis of Takayasu arteritis. Furthermore, a biopsy of the ulcerated skin lesion localized on the fibular surface showed a non-caseating cutaneous granulomatous lesion resulting in the diagnosis of cutaneous sarcoidosis. The simultaneous occurrence of cutaneous sarcoidosis and Takayasu arteritis, albeit rare, should not be overlooked.

[A CASE OF ADVANCED BLADDER NEUROENDOCRINE CARCINOMA (SMALL CELL CARCINOMA) SIGNIFICANTLY IMPROVED BY LOW DOSE OF ORAL TEGAFUR-URACIL].

A 81-old-woman underwent a transurethral resection of bladder tumor (TURBT) at a nearby hospital in April 2011. The diagnosis was invasive urothelial carcinoma, G3 with a component of bladder small cell carcinoma, T1 or more. She was recommended to visit our hospital for combined modality therapy of bladder cancer, but she refused the treatment for over one year. In May 2012, she came to our hospital with the chief complaint of pain at urination. Cystoscopy revealed non-papillary sessile tumor in the top of the bladder, and CT scan demonstrated the presence of the right obturator lymph nodes swollen up to 1.2 cm in size. The second TURBT was performed and the diagnosis was bladder small cell carcinoma (pT3N2M0) according to urothelial cancer guidelines of the Japanese Urological Association (JUA). Because she strongly refused hospitalization anymore, we started daily oral intake of low dose Tegafur-Uracil (100 mg) for the treatment. After one month, the serum Neuron-Specific Enolase (NSE; tumor maker of small cell cancer) level was elevated to 27.6 ng/ml and the right obturator lymph node was enlarged up to 1.9 cm. Therefore, the Trgafur-Uracil dose was increased to 200 mg daily. After then, the serum NSE level was decreased to 15.5 ng/ml following reduction in size of the obturator lymph nodes with partial response in December 2013. After two years of follow-up period, her regular urine test showed normal findings, and no apparent recurrence was detected on urinary bladder with MRI and Cystoscopy. This is a case of advanced bladder small cell carcinoma significantly improved by oral administration of Tegafur-Uracil 200 mg/day for over 2 years.

A case of acute kidney injury due to secondary retroperitoneal fibrosis caused by direct invasion of esophageal squamous cell carcinoma.

A 71-year-old man who developed renal failure was admitted to our hospital. Computed tomography without contrast enhancement showed bilateral hydronephrosis together with a soft tissue mass around the abdominal aorta, leading to the diagnosis of retroperitoneal fibrosis. Serum levels of immunoglobulin G4 were within the normal range. The patient was then evaluated for the presence of undiagnosed malignancy as a possible cause of secondary retroperitoneal fibrosis. Upper gastrointestinal tract endoscopy demonstrated esophageal cancer. Histology of the esophageal lesion and the retroperitoneal mass showed squamous cell carcinoma (SCC). Therefore, the retroperitoneal fibrosis was considered to be due to the invasion of SCC of the esophagus, and chemotherapy was chosen as the treatment. This is the first case report of postrenal failure due to secondary retroperitoneal fibrosis caused by the direct invasion of esophageal SCC. Physicians should be aware of occult malignancy as the cause of unexplained retroperitoneal fibrosis, even clinically silent, to avoid inappropriate management or delay in the treatment of potentially life-threatening co-morbidities.

Immunohistochemical findings and differential diagnosis of papillary-type cutaneous verrucous carcinoma of the neck: A case report.

Verrucous carcinoma (VC) is a rare subtype of squamous cell carcinoma, with the majority of cases occurring in the oral cavity and genital area. The present study describes a rare case of cutaneous VC of the neck manifesting as a semi-pedunculated multinodular protrusion. Histological analysis revealed thickening of the epidermis and papillary growth. Although cellular atypia was generally mild, a large number of mitoses were observed, of which a small number were abnormal. Additionally, bulbous subepidermal invasion was observed. The lesion was differentiated from papillary squamous cell carcinoma, another rare subtype of squamous cell carcinoma, based on the presence of epidermal verrucous growth and the lack of remarkable nuclear atypia. Benign disorders, including seborrheic keratosis, fibroepithelial polyp, verruca vulgaris and pseudocarcinomatous hyperplasia, were also differentiated from the lesion. Immunohistochemical analysis of cytokeratin (CK)10 expression revealed attenuated staining of the lesion, therefore, anti-CK10 immunohistochemistry may be valuable in the diagnosis of VC.

TNF-α receptor 1 expression predicts poor prognosis of diffuse large B-cell lymphoma, not otherwise specified.

We have previously shown that in tumor specimens from patients with diffuse large B-cell lymphoma, not otherwise specified (DLBCL, NOS), the tumor necrosis factor-α (TNF-α)-positive type correlates with a poorer prognosis compared with the TNF-α-negative type. In the present study, we further evaluated 60 lymphoma tissue specimens from patients with DLBCL, NOS by immunohistochemical staining with antibodies against TNF-α receptor 1 (TNFR1) and TNF-α receptor 2 (TNFR2). Our results demonstrated that 31 cases (52%) were positive and 29 (48%) were negative for TNFR1 and that the TNFR1-positive cases were significantly correlated with a poorer overall survival (OS; P=0.0006, log rank test) than the TNFR1-negative cases. The TNFR2-positive cases tended to have a poorer OS than the TNFR2-negative cases, although the difference was not significant. TNFR1 expression in tumor cells was a significant prognostic factor for OS and was independent of the International Prognostic Index (IPI). Among 31 TNF-α-positive DLBCL, NOS cases, 27 (87%) were positive and 4 (13%) were negative for TNFR1. Both TNF-α-positive and TNFR1-positive cases were significantly correlated with a poorer OS compared with the TNF-α-positive but TNFR1-negative cases. Twenty-seven cases (45%) with the TNF-α-positive and TNFR1-positive subtype of DLBCL, NOS had a poorer prognosis for OS and progression-free survival compared with the 33 cases (55%) with the remaining subtypes, and the TNF-α-positive and TNFR1-positive subtype of DLBCL, NOS was also shown to be independent of the IPI. In addition to the IPI, the prognosis of patients can be more accurately identified by evaluating both TNF-α and TNFR1 expression.