Predominance of T-bet-positive Th1 cells in infiltrating T-lymphocytes in most of active arteritis lesions of giant cell arteritis.

Immunological mechanisms through the activation of CD4-positive T-cells have been assumed to be involved in the pathogenesis of giant cell arteritis (GCA). Many studies employing frozen tissues of temporal artery biopsy, peripheral blood lymphocytes, and plasma of GCA patients have revealed the contribution of interferon-γ and interleukin-17 in both protein and mRNA levels. However, the analyses using formalin-fixed and paraffin-embedded (FFPE) tissue specimens, in which the correlation between histopathologic pictures and immunological circumstances would be elucidated, have been limited. Here, we performed the immunohistochemical analyses of infiltrating small lymphocytes in GCA lesions using FFPE specimens, especially of the subsets of CD4-positive T-cells by immunohistochemistry with antibodies against T-bet, GATA-3, RORγT, and Foxp3, which is the differentiation-specific transcription factor for Th1, Th2, Th17, and Treg cells, respectively. In these slides, the nuclear-positive staining is much more clearly and easily identifiable than the cytoplasmic staining for cytokines. The results indicate the predominance of T-bet-positive Th1 cells in infiltrating T-cells in most of active arteritis lesions of GCA. Furthermore, our data suggest the possible immunosuppressive microenvironment induced by T-reg cells and M2-type macrophages in the arteritis lesions throughout the course of GCA inflammation.

Successful Treatment of Epstein-Barr Virus Reactivation-associated Transverse Myelitis Following Herpes Zoster with Intravenous Rituximab in a Cord Blood Transplant Recipient.

The Epstein-Barr virus (EBV) is associated with many malignancies and autoimmune diseases, including multiple sclerosis. In addition, EBV rarely but occasionally causes central nervous system (CNS) complications. We herein report a case of transverse myelitis (TM) associated with systemic EBV reactivation after herpes zoster infection in a cord blood transplant recipient. Identification of EBV-infected peripheral blood cells revealed a predominance of B cells. Notably, intravenous rituximab ameliorated EBV reactivation and TM. Since the CNS infiltration rate of intravenous rituximab is markedly low, the clinical efficacy of rituximab against TM suggests that EBV reactivation may cause TM via immune-mediated mechanisms.

[Perforated upper gastrointestinal ulcers potentially attributable to mycophenolate mofetil after allogeneic hematopoietic stem cell transplantation].

A 46-year-old man with myelodysplastic syndrome/myeloproliferative neoplasm-unclassifiable underwent myeloablative bone marrow transplantation from an HLA-DR-1-antigen-mismatched related donor while receiving tacrolimus and mycophenolate mofetil (MMF) for graft-versus-host disease (GVHD) prophylaxis. However, grade III acute GVHD of the gut occurred on day 20 and was treated with prednisolone (PSL) and oral beclomethasone dipropionate while continuing MMF. Subsequently, he presented with progressive epigastric pain. Endoscopy demonstrated multiple stomach and duodenal deep ulcers. The ulcers were suspected to be GVHD; thus, the PSL dose was increased and infliximab was administered; however, the ulcers exacerbated, resulting in repeated perforations and hemorrhagic shock. Furthemore, MMF was suspected as the cause of refractory ulcers and was discontinued on day 156, which resolved the ulcers after 6 months. MMF-induced gastrointestinal (GI) injury resembles anti-inflammatory drug-related ulcers and upper and lower GI tract GVHD, respectively. MMF-induced GI injury has been reportedly resolved after discontinuing or reducing the MMF dose. Several reports suggested that refractory upper GI ulcers and rectal sparing colitis were associated with MMF toxicities rather than GVHD in hematopoietic stem cell transplantations. Physicians should be aware that MMF can induce severe GI injury.

Case report: Common clonal origin of concurrent langerhans cell histiocytosis and acute myeloid leukemia.

Langerhans cell histiocytosis (LCH) and acute myeloid leukemia (AML) are distinct entities of blood neoplasms, and the exact developmental origin of both neoplasms are considered be heterogenous among patients. However, reports of concurrent LCH and AML are rare. Herein we report a novel case of concurrent LCH and AML which shared same the driver mutations, strongly suggesting a common clonal origin.An 84-year-old female presented with cervical lymphadenopathy and pruritic skin rash on the face and scalp. Laboratory tests revealed pancytopenia with 13% of blasts, elevated LDH and liver enzymes, in addition to generalised lymphadenopathy and splenomegaly by computed tomography. Bone marrow specimens showed massive infiltration of MPO-positive myeloblasts, whereas S-100 and CD1a positive atypical dendritic cell-like cells accounted for 10% of the atypical cells on bone marrow pathology, suggesting a mixture of LCH and AML. A biopsy specimen from a cervical lymph node and the skin demonstrated the accumulation of atypical cells which were positive for S-100 and CD1a. LCH was found in lymph nodes, skin and bone marrow; AML was found in peripheral blood and bone marrow (AML was predominant compared with LCH in the bone marrow). Next generation sequencing revealed four somatic driver mutations (NRAS-G13D, IDH2-R140Q, and DNMT3A-F640fs/-I715fs), equally shared by both the lymph node and bone marrow, suggesting a common clonal origin for the concurrent LCH and AML. Prednisolone and vinblastine were initially given with partial response in LCH; peripheral blood blasts also disappeared for 3 months. Salvage chemotherapy with low dose cytarabine and aclarubicin were given for relapse, with partial response in both LCH and AML. She died from pneumonia and septicemia on day 384. Our case demonstrates a common cell of origin for LCH and AML with a common genetic mutation, providing evidence to support the proposal to classify histiocytosis, including LCH, as a myeloid/myeloproliferative malignancy.

The implicated clinical factors for outcomes in 304 patients with salivary duct carcinoma: Multi-institutional retrospective analysis in Japan.

BACKGROUND: Salivary duct carcinoma (SDC) is a high-grade salivary malignancy that frequently occurs as the carcinomatous component of carcinoma ex pleomorphic adenoma. We herein examined the clinical factors affecting outcomes in a large cohort of SDC. METHODS: We selected 304 SDC cases and investigated clinical characteristics and the factors affecting outcomes. RESULTS: The median age of the cases examined was 68 years, the most common primary site was the parotid gland (238 cases), and there was a male predominance (M/F = 5:1). Outcomes were significantly worse when the primary tumor site was the minor salivary glands (SG) than when it was the major SG. Outcomes were also significantly worse in pN(+) cases (161 cases) than in pN0 cases, particularly those with a metastatic lymph node number ≥11. The cumulative incidence of relapse and distant metastases was significantly higher in stage IV cases than in stage 0-III cases. CONCLUSIONS: The absolute number of lymph node metastases, higher stages, and the minor SG as the primary tumor site were identified as factors affecting the outcome of SDC.

Clinical Characteristics of Posttransplant Lymphoproliferative Disorder After Cord Blood Transplantation Without Antithymocyte Globulin.

BACKGROUND: CBT with ATG use is a well-known PTLD risk factor. However, little is known regarding the clinical features of PTLD after ATG-free CBT. PATIENTS AND METHODS: We analyzed the incidence, risk factors and prognosis of PTLD in 183 adults undergoing ATG-free CBT. RESULTS: Fifteen patients (diffuse large B-cell lymphoma, n = 9, mucosa-associated lymphoid tissue lymphoma, n = 2 nondestructive PTLD, n = 1, T-cell lymphoma, n = 3) developed PTLD. The 2-year CuI of PTLD was 8.0% (95% CI: 4.6-12.7). Pathologically, all 12 B-cell PTLD patients had Epstein-Barr virus (EBV), compared with 1 of 3 T-cell PTLD patients. All patients, excluding one with nondestructive PTLD, showed extranodal involvement. In the univariate analysis, the 2-year CuI of PTLD was significantly higher in patients who received mycophenolate mofetil to prevent graft-versus-host disease than in nonrecipients (11.2%/2.9%, P = .0457). However, multivariate analysis revealed no independent PTLD risk factors. All 11 PTLD patients who received specific therapy achieved complete remission. The 1-year overall survival of PTLD patients was 70.9%. CONCLUSION: Although we found a higher CuI of PTLD than previously reported, the prognosis was generally good. In CBT recipients, many factors, including MMF use, may be associated with the clinical features of PTLD.

Reliability of IDH1-R132H and ATRX and/or p53 immunohistochemistry for molecular subclassification of Grade 2/3 gliomas.

Since the World Health Organization 2016 classification (2016 WHO), genetic status has been incorporated into the diagnosis of Grade 2/3 gliomas (lower-grade gliomas). Therefore, immunohistochemistry (IHC) of IDH1-R132H, ATRX, and p53 have been used in place of genetic status. We report the associations between histological findings, IHC, and genetic status. We performed IHC of IDH1-R132H, ATRX, and p53 in 76 lower-grade gliomas and discussed its validity based on the 2016 WHO and the upcoming 2021 WHO classification. The sensitivity and specificity of anti-ATRX, p53, and IDH1-R132H IHC were 40.9%/98.1%, 78.6%/85.4%, and 90.5%/84.6%, respectively. Among 21 IDH1-mutant gliomas without 1p/19q codeletion, two gliomas (9.5%) mimicked the so-called classic for oligodendroglioma (CFO) in their morphology. Of the 42 gliomas with 1p/19q codeletion, four cases were difficult to diagnose as oligodendroglioma through morphological examination. Moreover, there were three confusing cases with ATRX mutations but with retained ATRX-IHC positivity. The lessons learned from this study are as follows: (1) ATRX-IHC and p53-IHC should be supplementary to morphological diagnosis, (2) rare IDH mutations other than IDH1 R132H should be considered, and (3) there is no complete alternative test to detect molecular features of glioblastoma under the 2021 WHO classification.

Serial Cancer Development Three Times in a Patient with Fanconi Anemia.

Fanconi anemia (FA) is characterized clinically by bone marrow failure, congenital malformations, sensitivity to DNA cross-linking agents, and increased risk of malignancy. Hematological cancer is the best-described malignancy in patients with FA, but the susceptibility to the development of solid tumors is also well documented, especially after hematopoietic stem cell transplantation (HSCT). With regard to the development of solid tumors in patients with FA, head and neck, esophageal, and anal squamous cell carcinoma are well known, but reports of lung cancer are extremely rare. Here, we describe an FA patient with a history of HSCT that developed 3 serial cancers - oral, esophageal, and nonsmall cell lung cancer - over a period of 6 years. The third lesion was nonsmall cell lung cancer and its location corresponded closely to the field of irradiation treatment for prior esophageal cancer. The occurrence of lung cancer in patients with FA is uncommon, but FA patients should be screened regularly and serially. Our case also indicated the importance of the irradiated field as a location for subsequent cancer development.

A rare case of high-grade intraductal carcinoma of the upper lip: immunohistochemical and genetic analyses.

Although intraductal carcinoma (IDC) of the salivary glands was previously called low-grade cribriform cystadenocarcinoma, it was newly categorized in the 4th version of the World Health Organization classification. We report a case of IDC of the upper lip and examined it immunohistochemically and genetically. The patient was a 48-year-old Japanese female, who noticed a tiny nodule on her left upper lip. Histologically, the tumor cells, which had eosinophilic cytoplasm, exhibited papillary and solid growth patterns, and regions of suspected microinvasion or intraductal spread were also seen at the periphery of the tumor. Small necrotic foci were noted. Immunohistochemically, the tumor cells were diffusely positive for the androgen receptor, CK19, CK5/6, EGFR, and SOX10, whereas they were focally positive for GCDFP-15, S-100 protein, and mammaglobin. The tumor nests were surrounded by alpha-smooth muscle actin-p63-/calponin-/CK14-positive myoepithelial cells. The Ki-67 labeling index was 51.2%. Genetic analysis showed no evidence of the TRIM27-RET or NCOA4-RET fusion gene. We finally diagnosed the tumor as a high-grade mixed intercalated duct/apocrine-type IDC of the upper lip. IDC of the minor salivary glands is exceedingly rare. We discuss diagnostic problems associated with minor salivary gland lesions, and the "basal-like" phenotype of this case.

CNS Low-grade Diffusely Infiltrative Tumors With INI1 Deficiency, Possessing a High Propensity to Progress to Secondary INI1-deficient Rhabdoid Tumors.

Atypical teratoid/rhabdoid tumors (AT/RTs) are highly malignant tumors of the central nervous system that predominantly occur in infants, and are characterized by the presence of rhabdoid cells and inactivation of INI1 or (rarely) BRG1. Most AT/RT are identified as primary tumors; however, rare AT/RT or INI1-deficient RTs arising from other primary tumors have been reported. Here, we report 3 cases of hitherto unclassifiable low-grade tumors with loss of INI1 nuclear expression, for which we propose the designation of central nervous system low-grade diffusely infiltrative tumors with INI1 deficiency (CNS LGDIT-INI1), 2 of which progressed to secondary RT. All 3 CNS LGDIT-INI1 exhibited a similar histology: diffusely distributed small tumor cells with round to oval or irregular nuclei and scant cytoplasm were admixed with degenerative neurons and large reactive astrocytes in an edematous, myxoid, or collagenous background. Mitotic figures were absent. Immunohistochemistry revealed that the tumor cells in all 3 CNS LGDIT-INI1 and 2 RT were negative for INI1. Genetically, total or partial homozygous deletions of the INI1 gene were detected in all CNS LGDIT-INI1 and RT excluding 1 CNS LGDIT-INI1 without sufficient DNA quality and quantity. Despite the loss of INI1 expression, these low-grade lesions were clearly distinguishable from AT/RT by their low proliferative activity, diffusely infiltrative growth pattern, and lack of rhabdoid cells and polyphenotypic immunoreactivity. In conclusion, CNS LGDIT-INI1 may represent a rare group of tumors that are clinically indolent but have a high propensity to progress to RT.

Alpha-type-1 Polarized Dendritic Cell-based Vaccination in Newly Diagnosed High-grade Glioma: A Phase II Clinical Trial.

BACKGROUND/AIM: Glioblastoma multiforme (GBM) is an intractable tumor that has a very poor prognosis despite intensive treatment with temozolomide plus radiotherapy. PATIENTS AND METHODS: Sixteen newly diagnosed patients with high-grade gliomas were enrolled in a phase II study of the α-type-1 DC vaccine. Briefly, DCs obtained from the culture of enriched monocytes in the presence of a cytokine cocktail, were pulsed with a cocktail of 5 synthetic peptides and cryopreserved until injection into patients. RESULTS: The amount of IL-12 produced by activated DCs was higher than that previously reported. Among 15 evaluable patients, 10 showed positive CTL responses to any peptides in an ELISPOT assay. After 6 years of observation, five patients were still alive, and two of these patients were relapse-free. Moreover, a significant survival-prolonging effect was verified in DC-treated glioma patients. CONCLUSION: Peptide-cocktail-pulsed α-type-1 DC vaccines have a potential therapeutic effect on survival when used in combination with the standard regimen, which is partly based on IL-12-IFN-γ-mediated T-cell activation.

Anaplastic transformation of thyroid cancer in mesentery metastases presenting as intestinal perforation: a case report.

BACKGROUND: Anaplastic thyroid carcinoma is a highly aggressive form of thyroid cancer associated with a very poor prognosis. Anaplastic transformation most commonly occurs in the thyroid itself or within regional lymph nodes. Here we report the case of a patient with papillary thyroid cancer, presenting with colon perforation as a result of anaplastic transformation of metastases in the mesentery tissue. There have been no previous reports of this form of anaplastic transformation. CASE PRESENTATION: A 74-year-old man was admitted to our hospital, presenting with abdominal pain that he had been experiencing for 1 week prior to admission. The patient had a history of papillary thyroid carcinoma, for which he underwent a total thyroidectomy and mediastinal lymph node dissection 6 years earlier, and subsequently received radioactive iodine therapy for postoperative recurrence in the lung 2 years later. During the present reported admission, a computed tomography scan revealed a large intra-abdominal mass infiltrating into the colon and retroperitoneum and also highlighted the pneumoperitoneum. The patient was diagnosed with generalized peritonitis as a result of colon perforation, as such, we conducted an emergency laparotomy. Intraoperative findings showed a mass affecting the ascending colon and kidney, following which, an ileostomy and biopsy were completed. Poorly differentiated spindle cells were identified in the biopsy specimens, and histopathological and immunohistochemical findings revealed the absence of thyroid carcinoma cells. The tumor was therefore believed to be a primary sarcoma. Following surgery, the patient recovered from sepsis that had arisen as a result of colon perforation, however, rapidly developed systemic metastases and died 1 month post-operation. An autopsy was performed, and the patient was diagnosed with anaplastic papillary thyroid cancer at the mesentery site of metastasis. This conclusion was reached owing to the presence of the squamous differentiation of lymph node cells, and because tumor cells were positive results for paired-box gene 8 expressions. CONCLUSIONS: Anaplastic transformation of papillary thyroid carcinoma should be considered in the diagnosis of a large mesentery mass in patients with a history of papillary carcinoma. An appropriate biopsy and paired-box gene 8 immunostaining can be useful in confirming such a diagnosis.

The ratio of CD163-positive macrophages to Iba1-positive macrophages is low in the intima in the early stage of cutaneous arteritis.

The etiology of polyarteritis nodosa (PAN) and localized PAN, including cutaneous arteritis (CA), remains unknown; however, initial endothelial damage has been implicated. The intima of the vasculitis lesions is predominantly infiltrated by innate-like bystander-activated CD8 T cells, in addition to the macrophages. Macrophages are among the major inflammatory cells involved in innate immunity and are classified into M1 and M2 subtypes. M1-type macrophages kill pathogens and cause inflammation, while M2-type macrophages promote the repair of tissues. Macrophage subtypes infiltrating in PAN and localized PAN vasculitis lesions have not yet been investigated. Innate immune response to a triggering factor on the endothelial cell surface may initiate CA pathogenesis. Thus, many M1-type macrophages may infiltrate in the intima during early CA. We assessed this hypothesis by immunohistochemical observation of macrophage phenotypes and polarization. Twenty-seven skin biopsy specimens from patients with CA were retrieved. Based on histology, we classified CA into four phases. The phenotypes of infiltrating macrophages in CA were evaluated by immunohistochemistry using antibodies against Iba-1, a pan-macrophage marker, and CD163, an M2-type macrophage marker. Our results showed that the ratio of CD163-positive M2-type macrophages to Iba1-positive macrophages was lower in the intima in the early stage of CA than in the later stage. In the media to adventitia, there was no significant difference in the ratios between these stages. These findings indicate that innate immunity is involved in the intima in the early stage of CA, suggesting that a trigger for CA might exist in endothelial cells.

A practical predictor of the growth potential of benign meningiomas: Hypointensity of surface layer in T2-weighted magnetic resonance imaging.

BACKGROUND: Accurate evaluation of proliferative potential is particularly important in the clinical management of individual patients with meningiomas. We introduce a new feature in the parenchyma of meningioma, namely, hypointensity of the surface layer (HSL), on T2-weighted MR images and compare it with a cellular proliferation index and growth speed. MATERIALS AND METHODS: We retrospectively analyzed the records of consecutive patients with WHO grade I meningiomas in two institutes: an operated group with 124 meningiomas resected in one institute, and an observed group with 89 meningiomas monitored without surgery in the other. Proliferative potential was evaluated using the MIB-1 labeling index (MIB-1 LI) for the operated group and using the relative growth rate on serial MR images for the observed group. RESULTS: In the operated group, 60 (48.4%) meningiomas exhibited HSL. HSL-positive meningiomas were significantly smaller in size and more often calcified than HSL-negative ones. Univariate analysis showed that HSL negativity, large size, no calcification, and surrounding brain edema were significantly associated with high MIB-1 LI (p < 0.05). Multivariate analysis demonstrated that only HSL was significantly related to MIB-1 LI (p = 0.001). HSL did not correlate with tumor recurrence after resection. In the observed group, 43 (48.3%) meningiomas exhibited HSL and they presented a significantly slow relative growth rate. CONCLUSIONS: HSL is a simple and new radiological feature indicative of low proliferative potential and a low risk of enlargement of meningiomas. The presence or absence of HSL may serve as a key parameter for the selection of aggressive treatment or active observation.

Pathological complete response by advanced hepatocellular carcinoma with massive macrovascular invasion to hepatic arterial infusion chemotherapy: a case report.

BACKGROUND: Advanced hepatocellular carcinoma (HCC) with macrovascular invasion has an extremely dismal prognosis. We report a rare case of multiple HCC with tumor thrombosis in the portal vein and inferior vena cava that was initially treated with hepatic arterial infusion chemotherapy (HAIC); later resection revealed pathological complete response. CASE PRESENTATION: A 75-year-old man presented with HCC in his right liver, with tumor thrombosis growing to the right portal vein and the inferior vena cava, and bilateral intrahepatic liver metastases. He underwent HAIC (5-fluorouracil [170 mg/m2] + cisplatin [7 mg/m2]) via an indwelling port. Although the tumor shrank and tumor marker levels decreased rapidly, we abandoned HAIC after one cycle because of cytopenia. We resumed HAIC 18 months later because of tumor progression, using biweekly 5-fluorouracil only [1000 mg] due to renal dysfunction. However, after 54 months, the HAIC indwelling port was occluded. The patient therefore underwent a right hepatectomy to resect the residual lesion. Histopathological findings showed complete necrosis with no viable tumor cells. The patient has been doing well without postoperative adjuvant therapy for more than 10 years after initially introducing HAIC and 6 years after the resection, without evidence of tumor recurrence. CONCLUSIONS: HAIC can be an effective alternative treatment for advanced HCC with macrovascular invasion.

Pro-gastrin-releasing peptide as a marker for the Ewing sarcoma family of tumors.

BACKGROUND: Pro-gastrin-releasing peptide (ProGRP) is an established tumor marker of small cell lung cancer. The purpose of this study was to determine if ProGRP could serve as a tumor marker for the Ewing sarcoma family of tumors (ESFTs). METHODS: Sixteen patients with ESFTs (mean age 32 years) were included in this study. As a control group, 42 patients with other tumor types that clinically or pathologically mimic ESFTs were also analyzed. Pre-treatment serum ProGRP and neuron-specific enolase (NSE) levels, the relationships between these levels, and tumor volume were investigated. In addition, serial changes in the serum or plasma ProGRP (6 patients) and NSE levels (5 patients) were measured over the course of treatment. RESULTS: Pre-treatment serum ProGRP levels were higher than the normal range in 8 of 16 patients; for these eight patients, ProGRP levels positively correlated with tumor volume (R = 0.99). In the control group, ProGRP levels were within the normal range, except for the two patients. Changes in ProGRP levels during treatment were consistent with tumor volume. Serum NSE levels were elevated in 14 of 16 patients with ESFTs and 8 of 42 patients with other tumor types. The range of NSE elevation was much smaller compared to that of ProGRP. Our data indicate that ProGRP is superior to NSE in terms of specificity. CONCLUSIONS: Serum ProGRP levels were elevated in half of the patients with ESFTs and reflected therapeutic response. ProGRP is a reliable tumor marker for the diagnosis of ESFTs and evaluation of treatment response.

Solitary peribronchiolar metaplasia showing a sub-solid nodule on computed tomography.

Recent advances in radiographic imaging and thoracic surgery have facilitated surgery for small lung tumors by eliminating the need for pathological diagnosis. To date, we have experienced two cases of small lung tumors that were surgically resected without pathological diagnosis as malignant. Computed tomography (CT) revealed sub-solid nodules in the peripheral lung. After tumor resection, both tumors were pathologically diagnosed as peribronchiolar metaplasia. To the best of our knowledge, solitary peribronchiolar metaplasia showing a sub-solid nodule on CT imaging has not previously been reported.

Pulmonary mucormycosis developed during acute myelogenous leukemia and successfully treated by surgical resection before blood stem cell transplantation.

Pulmonary mucormycosis is relatively rare and occurs in immunosuppressed patients, for example, individuals with hematologic malignancies such as leukemia. As pulmonary mucormycosis increases rapidly and is often fatal, appropriate treatment including surgical resection is necessary. We report a patient with pulmonary mucormycosis and acute myelogenous leukemia for which antifungal drugs were invalid. After rapid surgical resection, the patient was administered a peripheral blood stem cell transplantation. In conclusion, we emphasize that patients with pulmonary mucormycosis undergoing leukemia treatment should be considered for rapid surgical treatment if the infected lesion is limited, as overcoming this acute infection increases their chance to undergo hematopoietic stem cell transplantation and potential for long-term survival.

Lambert-Eaton Myasthenic Syndrome Associated with Synchronous Double Cancer: A Combination of Small Cell Carcinoma of the Cervix and Breast Carcinoma.

Lambert-Eaton myasthenic syndrome (LEMS) is most commonly associated with small cell lung carcinoma, while it is rarely associated with gynecological and breast carcinoma. We herein report a case of LEMS associated with synchronous double cancer, which was a combination of small cell carcinoma of the cervix and breast carcinoma. The early diagnosis and treatment of LEMS are important for achieving a good outcome. The possibility of accompanying paraneoplastic neurological syndrome must be sufficiently considered in gynecology and breast cancer patients. To our knowledge, this is the first report of LEMS associated with synchronous double cancer.

Osteogenic differentiation in dedifferentiated liposarcoma: a study of 36 cases in comparison to the cases without ossification.

AIMS: Ossification is found occasionally in dedifferentiated liposarcoma (DDLPS). The aims of this study were to elucidate whether the formed bone tissue is usually produced by tumour cells or by reactive non-neoplastic cells, and to reveal the clinicopathological characteristics of DDLPS with ossification. METHODS AND RESULTS: We examined 36 cases of ossified DDLPS by comparing them to 31 cases of non-ossified DDLPS. MDM2 amplification was confirmed in osteocytes and/or osteoblastic cells in all but one ossified DDLPS cases (27 of 28) using fluorescence in-situ hybridisation, although the morphological impression of ossification appeared to be mainly metaplastic (27 of 36) or high-grade osteosarcoma-like (six of 36). The bone tissue was often formed predominantly at the periphery of the DDLPS area near the well-differentiated liposarcoma component (18 of 36), and an organised structure such as bone marrow-like differentiation was not uncommon (12 of 36). According to a modified French Fédération Nationale des Centers de Lutte Contre le Cancer (FNCLCC) grading system, ossified DDLPS tended to be lower grade than non-ossified DDLPS (mean grade: 1.88 and 2.15, respectively). Ossification in DDLPS was associated significantly with shorter local recurrence-free survival by multivariate analysis (P = 0.02347), but metaplastic-appearing ossification tended to be associated with longer overall survival (P = 0.1400). CONCLUSIONS: The bone tissue formed in DDLPS was mainly neoplastic regardless of its morphology and maturity, which highlighted the osteogenic differentiation of the tumour cells. DDLPS patients with osteogenic differentiation tended to suffer from earlier local recurrences, which did not necessarily lead to poor life outcomes.