The association between CD34 expression status and the clinicopathological behavior of dedifferentiated liposarcoma.

Lipogenic and fibrous tumors are thought to originate from CD34-positive stromal fibroblastic/fibrocystic cells. Well-differentiated lipogenic tumors typically express CD34, whereas dedifferentiated liposarcoma (DDLPS) often loses it. We conducted survival analyses involving 59 patients with DDLPS. Males comprised 53% of the cohort, and the median age at the time of wide resection of primary DDLPS was 60 years. Loss of CD34 expression was defined as when ≥50% of the dedifferentiated area was immunohistochemically negative for CD34. As a result, 39 of the 59 patients showed loss of CD34 expression during the initial operation for DDLPS. In the univariate analyses, the tumor site in the retroperitoneum/abdominal cavity and loss of CD34 expression were significantly associated with poor overall survival. In the multivariate analyses, loss of CD34 expression (HR = 2.26; 95% CI = 1.02-5.02; p = 0.04) and the tumor site in the retroperitoneum/abdominal cavity (HR = 3.11; 95% CI = 1.09-8.86; p = 0.03) were retained as independent prognostic factors. Six CD34-positive cases lost CD34 expression when they developed metastasis and/or local recurrence, suggesting that the loss was associated with the later stage of the tumor. Therefore, an association existed between the loss of CD34 expression and clinicopathological behaviors such as poorer prognoses and recurrence.

[A case of fibrolamellar hepatocellular carcinoma mimicking a liver abscess].

A 23-year-old woman was presented with fever and epigastric pain. Contrast enhanced computed tomography revealed a 40mm mass in the lateral segment. Blood tests showed the elevation of WBC and CRP. With the diagnosis of liver abscess, the antibiotics were administered, and the clinical findings were promptly improved. One year later, she complained of the same symptoms, and the mass had increased to 50mm in diameter. Percutaneous liver biopsy led to the diagnosis of fibrolamellar hepatocellular carcinoma.

Simultaneous occurrence of accelerated nodulosis in lungs, liver, and kidneys, and acute exacerbation of interstitial pneumonia in a patient with rheumatoid arthritis: an autopsy case report.

BACKGROUND: Accelerated nodulosis (ARN) is a rare variant of rheumatoid nodules (RNs) that is characterized by a rapid onset or the worsening of RNs. It generally develops at the fingers in patients with rheumatoid arthritis (RA) receiving methotrexate (MTX). Few case reports have described ARN at an extracutaneous location. CASE PRESENTATION: An elderly patient with long-standing RA was admitted to our hospital with acute respiratory failure. Computed tomography upon admission showed diffuse ground-glass opacities superimposed with subpleural reticular shadowing and honeycombing and multiple nodules in the lungs and liver. Despite the discontinuation of MTX and introduction of an immunosuppressive regimen with pulse methylprednisolone followed by a tapering dose of prednisolone and intravenous cyclophosphamide, the patient died due to the acute exacerbation (AE) of RA-related interstitial lung disease (ILD) following the parallel waxing and waning of a diffuse interstitial shadow and pulmonary and liver nodules. At autopsy, RNs were scattered throughout both lung fields in addition to extensive interstitial changes. RNs were also detected in the liver and kidneys. The foci of cryptococcosis were mainly identified in alveolar spaces. Based on the clinical and pathological findings, these nodules were most consistent with ARN because of acute increases in the size and number of previously detected pulmonary nodules. CONCLUSION: The present case is noteworthy because ARN was concurrently detected in multiple internal organs and may be associated with the AE of RA-related ILD.

High prevalence of TERT aberrations in myxoid liposarcoma: TERT reactivation may play a crucial role in tumorigenesis.

Myxoid liposarcoma (MLPS) is genetically characterized by FUS-DDIT3 or EWSR1-DDIT3 gene fusion and the high frequency of hotspot mutations (C228T or C250T) in the promoter region of telomerase reverse transcriptase (TERT) that encodes the TERT protein. The latter leads to telomerase reactivation, a mechanism of telomere maintenance. Although the TERT promoter hotspot mutation is a poor prognostic factor in various tumors, its effect on MLPS has not been reported in detail. In the present study, we examined the clinicopathological characteristics, prognosis, and telomere maintenance mechanisms in 83 primary tumor samples of MLPS, which were resected surgically at the Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan, from 2008 to 2020. TERT promoter hotspot mutations were observed in 77% (63/82) cases, and alternative lengthening of telomeres (ALT) was absent in all cases. Among the cases without TERT promoter hotspot mutations, TERT rearrangements, and minor point mutations in the TERT promoter region were found in 3 and 2 cases, respectively. TERT mRNA expression was observed consistently even in patients for whom no genomic TERT aberrations were detected, and the presence of TERT promoter hotspot mutation did not correlate significantly with either overall and metastasis-free survival (P = .56, P = .83, respectively) or clinicopathological features. Therefore, patients with MLPS characteristically shows TERT expression and a high prevalence of TERT aberrations. Our findings suggest that TERT aberration is not prognostic factor, but might occur at an early stage and play a key role in tumorigenesis.

S100-negative epithelioid malignant peripheral nerve sheath tumor with possible perineurial differentiation.

Epithelioid malignant peripheral nerve sheath tumor (MPNST) is a rare subtype of MPNST composed of epithelioid cells with abundant cytoplasm. Currently, strong and diffuse immunostaining for S100 protein and SOX10 is generally regarded as a characteristic feature of epithelioid MPNST. However, malignant tumors with epithelioid morphology that arise from a peripheral nerve or a pre-existing benign nerve sheath tumor should be regarded as epithelioid MPNSTs when they do not show characteristic features that definitively lead to other specific diagnoses. Here, we describe 3 cases of epithelioid MPNST in the peripheral nerve or schwannoma that was negative for S100 protein and SOX10 expression. Instead, these tumors were positive for EMA, GLUT1, claudin 1, and cytokeratin to varying degrees, while all of them retained SMARCB1 and H3K27me3 by immunohistochemistry. EMA, GLUT1, and claudin 1 are known markers of perineurial cell differentiation; thus, they could possibly represent epithelioid MPNST with perineurial cell differentiation.

[A Case of Rectal Cancer with Hemorrhagic Shock with Bleeding Controlled via Stent Placement That Underwent Radical Resection after Preoperative CRT].

Colorectal stents are used mainly for the palliative treatment of colorectal obstruction or preoperative re-obstruction. However, the hemostatic effect of covered stents reportedly induced bleeding of esophageal cancer and varicosities. Here, we report a case of mildly obstructed rectal cancer with severe anemia and hemorrhagic shock that resulted in pulsatile tumor bleeding. Curative surgical resection was performed successfully after the administration of chemoradiotherapy. The patient was a 67-year-old man. A nearby doctor diagnosed him with anemia(Hb 4.6 g/dL)and referred him to our hospital, where he was diagnosed with rectal cancer at the Ra position. He was immediately hospitalized owing to voluminous melena, loss of consciousness, and hematoma formation on the posterior aspect of the head. Urgent CF was performed due to persistent melena and decreased blood pressure. The pulsatile bleeding from rectal cancer was identified. To address the diffuse bleeding, a covered stent was placed to induce hemostasis and dilation. This also served as a bridge to surgery( BTS). Hemostasis was successfully achieved. After chemoradiotherapy( CRT), a laparoscopic low anterior resection was performed. Radical surgery was performed, and S-1 was taken 6 months postoperatively. At 2 years postoperatively, metastatic recurrence was not observed.

Prognostic value of CD34 expression status in patients with myxofibrosarcomas and undifferentiated pleomorphic sarcomas.

It is controversial whether patients with myxofibrosarcomas (MFSs) have better prognoses than those with undifferentiated pleomorphic sarcomas (UPSs). No useful prognostic factors have been established to date. We therefore aimed to evaluate the prognostic value of CD34 expression status in 192 patients with MFSs and UPSs. Using the log-rank test, we showed that patients with MFSs had a significantly better overall survival than did those with UPSs when defining the former as having a > 10% myxoid component (p = 0.03), but not when defining it as having a > 50% myxoid component (p = 0.1). Under the definition of MFSs as > 10% myxoid component, the log-rank test revealed that the diagnosis of the UPS and the CD34 loss (p < 0.001) were significant adverse predictors of overall survival. As per the Cox model, the CD34 loss remained an independent prognostic factor (hazard ratio = 3.327; 95% confidence interval 1.334-8.295), while the diagnosis of the UPS was a nonsignificant confounding factor (hazard ratio = 1.084; 95% confidence interval 0.679-1.727). In conclusion, CD34 expression status is a useful prognostic factor in patients with MFS and UPS, and it should be incorporated into grading systems that are used to predict outcomes.

Giant cell tumor of soft tissue of the breast: Case report with H3F3A mutation analysis and review of the literature.

Giant cell tumors of soft tissue (GCT-ST) arising in the breast are extremely rare. We report a unique case of breast GCT-ST coincident with ductal carcinoma in situ (DCIS), diagnosed with histological, immunohistochemical, and H3F3A (Histone H3.3) mutation analyses. A 59-year-old woman preoperatively diagnosed with DCIS underwent total mastectomy for a cystic mass. Histology revealed a tumor composed of mononuclear cells interspersed with numerous osteoclast-like giant cells, resembling giant cell tumor of bone (GCT-B), with apocrine DCIS in proximity to the tumor. The mononuclear and giant cells were immunoreactive for CD68 and negative for cytokeratins. Granulomatous diseases, carcinomas with giant cells, and giant cell-type sarcomas were excluded by histological and immunophenotypic features. Lack of H3F3A mutation eliminated the possibility of GCT-B metastasizing to the breast. These findings were consistent with GCT-ST of the breast. To our knowledge, this is the ninth reported case of breast GCT-ST, but the first case that accompanied DCIS or involved H3F3A mutation status investigation. For correct diagnosis of this rare tumor, it is important for pathologists to raise the possibility of GCT-ST when encountering giant cell-rich breast lesions and to exclude other differential diagnoses by combining the results of histological, immunohistochemical, and genetic analyses.

Osteosarcoma arising in fibrous dysplasia, confirmed by mutational analysis of GNAS gene.

Malignancy arising in fibrous dysplasia (FD) is rare. Approximately 100 cases have been reported so far, and osteosarcoma is the most common malignancy. We report a case of osteosarcoma in a 33-year-old Japanese man with monostotic FD of the right proximal femur from the age of 16 years. Histologically, relatively well-differentiated osteosarcoma was found in the FD lesion. Immunohistochemically, the FD was negative for p53 or MDM2, and the MIB-1 index was less than 1%, whereas the osteosarcoma was positive for both p53 and MDM2, and the MIB-1 index was up to 15%. The FD and osteosarcoma were negative for CDK4. Fluorescent in situ hybridization assay showed no amplification of the MDM2 gene, indicating that the osteosarcoma was a conventional osteosarcoma, not an intraosseous well-differentiated type. The original cell of malignancy in FD is unclear. Malignancy can be potentially derived from dysplastic cells in the area of the FD or cells in the adjacent normal tissues. GNAS gene mutation has recently been reported for fibrous dysplasia and the mutation is highly specific to fibrous dysplasia among fibro-osseous lesions including osteosarcoma. In this case, point mutations of GNAS were found in the FD and osteosarcoma but not in the adjacent normal tissues, suggesting that osteosarcoma was derived from the spindle cells of FD. This is the first report to clearly show that osteosarcoma is derived from the spindle cells in fibrous dysplasia (FD).

Systemic lupus erythematosus as the concomitant manifestation of angioimmunoblastic T-cell lymphoma.

Herein we report a case of the simultaneous occurrence of angioimmunoblastic T-cell lymphoma (AITL) and systemic lupus erythematosus (SLE) in a 76-year-old woman. She presented with fever, night sweats, and general malaise. A laboratory examination revealed leukopenia, anemia, polyclonal hypergammaglobulinemia, hypocomplementemia, positive results for anti-nuclear antibodies and anti-double strand DNA (anti-dsDNA) antibodies, and mild proteinuria. A computed tomography scan of the abdominal cavity showed multiple swollen intra-abdominal and intra-pelvic lymph nodes. A biopsy specimen obtained from the peri-iliac lymph node confirmed the diagnosis of AITL, while renal biopsy results were consistent with lupus nephritis, International Society of Nephrology and Renal Pathology Society class V. These results indicated that our patient developed SLE concomitantly with AITL. These findings will lead to further understanding of the pathogenic mechanism of SLE.

Hepatoid tenosynovial giant cell tumor - a rare morphologic variant case report.

We report a morphologically rare type of tenosynovial giant cell tumor (TSGCT), localized type, occurring in a 49-year-old man. Imaging examination revealed multiple nodular lesions around the right knee joint. The largest one extended to both intra- and extra-osseous region of the right distal femur. Histologically, the tumor consisted of epithelioid mononuclear cells and they looked like to have abundant eosinophilic cytoplasm reminiscent of hepatic tissues. In some areas, however, typical histologic features of TSGCT were observed. Electron microscopy revealed that the eosinophilic cytoplasm-like substance was intercellular fibrinous material surrounding the mononuclear tumor cells. Immunohistochemically, mononuclear tumor cells and multinucleate giant cells were positive for CD68 (Kp1) and some of the mononuclear tumor cells were also positive for desmin. Finally, we made the diagnosis of hepatoid TSGCT.

[A very elderly case of complete remission by chemotherapy in a patient of primary esophageal non-Hodgkin lymphoma].

A very elderly patient with primary non-Hodgkin lymphoma of the esophagus is reported. An 87-year-old woman presented with dysphagia. Endoscopy revealed an elevated lesion with ulceration in the middle and lower esophagus. Endoscopic biopsy demonstrated pathological diagnosis and immunochemistry typical of non-Hodgkin lymphoma (Ann Arbor stage IIIEA), diffuse large B-cell lymphoma on the WHO classification. Systemic chemotherapy with 6 courses of a 50% dose of R-CHOP followed by 8 courses of rituximab for maintenance, successfully resulted in complete remission. Complete remission has been maintained for 58 months.

[A case of advanced rectal cancer with multiple liver metastases successfully treated by perioperative administration of UFT and oral leucovorin].

The patient was a sixty-five-year-old man who had an advanced rectal cancer (Ra, type 2) with liver metastases. Low anterior resection with lymphnode dissection (D3) was done, but hepatectomy was not performed because of the multiple metastases besides the five tumors detected preoperatively. The pathological finding was moderately-differentiated adenocarcinoma. He was treated with 5-FU via the hepatic artery, but the therapy failed due to catheter infection after 3 postoperative months. Then, he received general 5-FU/l-LV therapy intravenously from 3 to 8 months after the operation, and oral UFT/LV (Uzel®) from 9 to 22 months. Next, we switched to single UFT therapy at 23 months because CT findings showed remarkable calcification in the liver metastases. But only one tumor of the liver (S6) among liver metastases enlarged at 27 months. We switched the chemotherapy again to UFT/Uzel and mFOLFOX6, but decided to perform hepatectomy of S6/7 at 39 months since it proved ineffective. The pathological finding was 90% necrosis and calcification of the tumor. Metastasis of the right 10th rib was newly found and was removed at 63 months after the first operation. Now, NC in the liver is continued 67 months after the first operation, and the patient is doing well.

The topoisomerase II alpha gene status in primary breast cancer is a predictive marker of the response to anthracycline-based neoadjuvant chemotherapy.

This study aimed at evaluating the usefulness of topoisomerase II alpha (TOP2A) for predicting the effect of anthracycline-based neoadjuvant chemotherapy in breast cancer. The TOP2A status was examined using fluorescent in situ hybridization (FISH) in 14 pre-chemotherapeutic breast cancer tissues, and was also assessed by immunohistochemistry (IHC) in 14 pairs of pre- and post-chemotherapeutic breast cancer specimens. TOP2A gene aberration by IHC tended to show a correlation with pathological responses but this was not statistically significant (p=0.060). On the other hand, the low TOP2A/CEP17 ratio correlated with good pathological responses (p=0.012). TOP2A overexpression was not significantly associated with response (p=0.580). Our results thus suggest that the TOP2A/CEP17 ratio may be a useful predictor of the effects of anthracycline-based neoadjuvant chemotherapy in breast cancer.

Dedifferentiated liposarcoma with rhabdomyoblastic differentiation in an 8-year-old girl.

The development of a liposarcoma during childhood is extremely rare. We report a case of dedifferentiated liposarcoma arising in the left thigh of an 8-year-old girl. Morphological and immunohistochemical studies revealed occasional rhabdomyoblastic differentiation in the dedifferentiated component. The identical cells were co-mingling with the well-differentiated liposarcoma component. This is the first description of such a case of liposarcoma occurring in a child.

Carcinosarcomatous malignancy, osteosarcoma and squamous cell carcinoma, in giant cell tumor of the right distal femur.

We report a new type of secondary malignant giant cell tumor of bone, the malignancy of which was assigned to a carcinosarcoma, i.e., osteosarcoma and squamous cell carcinoma. It occurred 25 years after curettage and bone graft surgery under the diagnosis of giant cell tumor of the right distal femur. Although secondary malignant giant cell tumor is known as a sarcoma arising at the site of a previously diagnosed giant cell tumor, this case should be regarded as a new type of secondary malignant giant cell tumor of bone.

A Japanese patient with Li-Fraumeni syndrome who had nine primary malignancies associated with a germline mutation of the p53 tumor-suppressor gene.

We describe a patient who had nine primary malignant tumors and a germline mutation in the p53 tumor-suppressor gene, characteristically found in the Li-Fraumeni syndrome (LFS). A 15-year-old girl with no family history of cancer was referred to our hospital because of pain and swelling of the right knee. Osteosarcoma was diagnosed. The patient received chemotherapy followed by surgery and had a remission. After the age of 28 years, nine primary malignant tumors developed successively, including right breast cancer, colon cancer, malignant fibrous histiocytoma (MFH) of the abdominal wall, right lung double cancers, bilateral breast cancers, and MFH of the left thigh. This is the second highest number of types of primary malignant tumors to be reported in LFS. All tumors were treated by a multidisciplinary approach, including surgery. Genetic analysis revealed a germline missense mutation in the p53 gene (c.659 A > G), resulting in Y220C, which has been reported in three families with LFS. The patient died of lung metastasis from MFH at the age of 37 years. Despite the multiple tumors, repeated induction of remissions resulted in long survival. Our findings suggest that a multidisciplinary approach to treatment, including surgery, is beneficial in patients with LFS.

Different immunophenotypes in Buerger's disease.

Recently, we reviewed the morphology of 31 specimens of thromboangiitis obliterans (TAO, Buerger's disease) in a multivariate analysis and showed that certain novel features of the affected vessels are different from arteriosclerosis obliterans (ASO) and thromboembolism. However, the pathogenic concept of TAO is still controversial. We applied immunohistochemistry to 58 amputated lower extremities and five autopsy controls. At specific sites of the diseased vessels, different cellular components were immunotyped by CD3, CD4, CD20, CD31, CD68, actin and desmin. These results were carefully compared among different diagnostic groups of vasoocclusive lesions by statistical methods. Some unique characteristics of TAO were identified when compared with ASO or thromboembolism. Consistent with a primary inflammatory and immunogenic lesion, lymphocytes and especially CD4+ T cells emerged significantly in TAO vessels and their adventitia. In the subset of definite TAO cases defined by all clinical criteria, the linear arrangement of macrophages, and B- and T-lymphocytes along vascular elastic fibers was the most striking additional finding, suggesting elastic fibers are an important immunogen. However, this feature was not apparent in closely related cases, otherwise similar to TAO and different from ASO and thromboembolism. Thus, our results indicate a heterogeneous group of TAO diseases, suggesting that damage to elastic fibers may be a secondary change to primary inflammation.

[Phase III additional clinical study of 111In-pentetreotide (MP-1727): diagnosis of gastrointestinal hormone producing tumors based on the presence of somatostatin receptors].

Additional phase III multicenter clinical study was performed to investigate the efficacy, safety, and usefulness of somatostatin receptor scintigraphy using 111In-pentetreotide (MP-1727), which binds to somatostatin receptors. Forty patients were included in the study; Group A: 18 patients, gastrointestinal hormone producing tumors had been detected with conventional imaging modalities, Group B: 22 patients, no tumors had been detected with conventional imaging modalities in spite of high serum hormone levels. By comparing the results of the octreotide suppression test, 12/16 cases (75.0%) of Group A and 11/19 cases (57.9%) of Group B were assessed as "effective." By comparing the results of immunohistological examination, 5/9 cases (55.6%) of Group A and 2/4 cases (50.0%) of Group B were assessed as "effective." Severe adverse events were not observed in any of the evaluable 35 cases. MP-1727 was judged as clinically useful in 11/16 cases (68.8%) of Group A and 5/19 cases (26.3%) of group B. These results suggest that MP-1727 scintigraphy is very useful for the diagnosis and decision of the therapeutic strategy of gastrointestinal hormone producing tumors.