Search

Ossifying fibromyxoid tumor (OFMT) is a rare soft tissue neoplasm of uncertain differentiation that has the capacity for local recurrence and metastasis. Many OFMTs, including typical, atypical, and malignant tumors, have demonstrated recurrent gene fusions. The fusion partners reported to date share a common core function in that they play either a direct or indirect role in processes influencing histone modification. Herein, we report an OFMT with unusual morphology and non-specific immunoprofile harboring a novel MEAF6-SUZ12 fusion. A 34-year-old male presented with a slowly growing mass in the right antecubital fossa. Excision demonstrated a 6.9 cm partially encapsulated, tan-white, lobulated, and calcified lesion. Microscopic evaluation demonstrated cytologically bland spindle to ovoid cells arranged in a haphazard manner within a fibromyxoid background containing dense collagen, often with sclerotic nodules, and randomly distributed ossification. The tumor cells were diffusely positive for CD34 while essentially negative for S100, desmin, MUC4, SOX10, AE1/3, SMA, and EMA. Next-generation sequencing studies (sarcoma gene fusion next-generation sequencing panel with subsequent Sanger confirmation) performed on formalin-fixed paraffin-embedded tissue detected a fusion product between MEAF6 exon 4 (NM_001270875) and SUZ12 exon 2 (NM_001321207.1). The proposed mechanism of pathogenesis in OFMT, namely epigenetic dysregulation, is reinforced by the fact that both of these partner genes are involved in histone modification.

T-cell prolymphocytic leukemia (T-PLL) is a rare, aggressive neoplasm derived from post-thymic T-cells. Patients are typically middle aged with a slight male predominance who present with a high white blood cell count, hepatosplenomegaly, lymphadenopathy, and other symptoms typically associated with leukemia. Although cutaneous involvement has been reported in up to 30% of cases of T-PLL, to our knowledge, none have presented with a presentation resembling livedoid vasculopathy. In the correct clinical context, an underlying hematolymphoid neoplasm should be included in the differential diagnosis of a patient presenting with livedoid vasculopathy.

Myoepithelial tumors of soft tissue are rare mesenchymal neoplasms that overlap with their salivary gland and skin counterparts at both the histopathologic and molecular levels. EWSR1 gene rearrangements with various fusion partners represent a common genetic event in myoepithelial tumors of soft tissue, whether benign or malignant, and may prove useful as a diagnostic tool in difficult cases. However, the number of diagnostic entities with EWSR1 gene rearrangements has grown considerably in recent years, and there is significant morphologic and immunophenotypic overlap amongst this group, underscoring the importance of fusion testing to detect fusion partners that are characteristic of discrete diagnostic entities. Herein, we report a malignant myoepithelial tumor of soft tissue/myoepithelial carcinoma with an undifferentiated round cell morphology arising in a pediatric patient with a EWSR1-ATF1 gene fusion.

SMARCA4-deficient thoracic sarcoma (SMARCA4-DTS) is a recently recognized entity with undifferentiated rhabdoid morphology and mutations in the switch/sucrose nonfermenting BRG1-associated factors complex. Patients are typically males in their fifth decade with a history of smoking who present with rapidly progressive intrathoracic disease and follow an aggressive clinical course. Metastatic disease is reported in up to 77% of cases; however, to our knowledge, cutaneous metastasis has not been reported nor has it been reported as the initial manifestation of the disease. Recognizing SMARCA4-DTS from other types of epithelioid tumors that involve the skin is clinically relevant, as targeted therapies for SMARC-deficient tumors are currently being investigated and early clinical trial data show therapeutic benefit.

Background: Biologic augmentation via extracellular matrix (ECM) scaffolds has been utilized to address rotator cuff tears with poor-quality tissue. Purpose: To evaluate the cellular changes in graft explants taken from patients treated with porcine dermal grafts for rotator cuff tears. Study Design: Case series; Level of evidence, 4 Methods: Four graft biopsy specimens were obtained from patients treated with porcine dermal grafts in an interposition technique for rotator cuff tears and compared with a nonimplanted graft and a normal rotator cuff specimen. Biopsy of the graft site was performed at 18 days, 3 months, 7 months, and 10.5 months after implantation. Hematoxylin and eosin staining was used to evaluate for cellular and vascular changes. Picrosirius red (PSR) stain with 90° polarized light was performed to evaluate collagen fibril size and orientation. All biopsy specimens were analyzed by a pathologist. Results: There was evidence of progressive remodeling of the porcine dermal grafts. The most mature grafts demonstrated vessel infiltration and extensive remodeling without evidence of inflammation, foreign body reaction, or tissue rejection. PSR demonstrated increased organization of collagen domains, resembling normal tendon by 10.5 months postoperatively. Conclusion: This series suggests that ECM grafts may serve as an effective scaffold for host cell infiltration, collagen reorganization, and vascularization as a result of histologic changes demonstrated with retrieval of specimens from patients with rotator cuff tears that were augmented with porcine dermal grafts.

Introduction. Fibrosarcomas, once comprising the majority of unclassifiable spindle-cell sarcomas, are now regarded as a diagnosis of exclusion. Objectives. Prompted by an index report of neurotrophic receptor tyrosine kinase (NTRK)3 fusion in fibrosarcomas by Yamazaki et al bone/soft tissue tumors diagnosed as fibrosarcoma at our institution were evaluated in an attempt to expand the genetic spectrum of fibrosarcomas and identify therapeutically targetable cases. Methods. Institutional archives were searched for cases diagnosed as “fibrosarcoma” involving bone/soft tissue from 2000 to present. Twenty-one cases meeting inclusion criteria were identified, 10 of which had formalin-fixed paraffin-embedded tissue available for molecular testing. One case, at the submitting clinician's request, underwent outside deoxyribonucleic acid/ribonucleic acid (DNA/RNA) sequencing while the 9 remaining cases underwent in-house next-generation sequencing RNA fusion analysis. Results. At the time of diagnosis the mean age was 54.5 (range 14-88) with a male to female ratio of 1.5:1. Locations included soft tissue of the lower extremity (3), trunk (2), pelvis (2), head (1), upper extremity (1), and bone (1). Of the 10 cases, 1 demonstrated an FNDC3B-PIK3CA gene fusion and 1 demonstrated a BRAF (p.G469A ) mutation and CDKN2A/B loss. Conclusion. In conclusion, our study demonstrated gene fusions in 1 (10%) of 10 fibrosarcomas diagnosed at our institution in the past 20 years, including FNDC3B-PIK3CA gene fusion. Additionally, 1 case harbored BRAF (p.G469A) mutation and CDKN2A/B loss with no evidence of gene fusion. NTRK rearrangements were not detected. The significance of these molecular aberrations is presently unclear and future studies are needed to establish whether these findings carry any clinicopathologic significance.

Background Disabled-2 (Dab2) is known as a tumor suppressor as well as a Wnt pathway inhibitor. We previously reported that Dab2 was down-regulated due to gene promoter hypermethylation in lung cancer. Here, we aim to study if X-ray irradiation can induce de-methylation of the Dab2 gene and subsequently up-regulate its expression, and also to attempt to suppress the malignant biological behavior of and enhance the radiosensitivity in lung cancer cells with hypermethylation of the Dab2 gene. Methods Immunostaining was performed to investigate the relationship between Dab2 expression and lung cancer clinicopathological characteristics. Bisulfite sequencing PCR (BSP) was used to evaluate the methylation status of lung cancer cells with or without X-ray treatment. Real-time PCR and western Blot were performed to investigate the expression of Dab2, Wnt pathway factors, DNMTs and methyl CpG binding protein 2 (MeCP2). Colony Formation, matrigel invasion and xenograft experiment were performed to evaluate the malignant biological behavior of lung cancer cells with irradiation. Results The result of immunostaining of Dab2 in lung cancer tissues showed that decreased Dab2 expression was positively correlated with poor differentiation, lymph node metastasis, advanced TNM stage and poor prognosis. X-ray treatment significantly up-regulated Dab2 expression and inhibited Wnt factors in LK2 cells (with hypermethylation of the Dab2 gene promoter, P

Pleuropulmonary blastomas (PPB) are rare aggressive paediatric lung malignancies associated withDICER1variants. We present two cases, a 2-year-old girl with upper respiratory tract symptoms as well as a 6-month-old girl sibling undergoing screening due to family history of malignancy. Imaging of the 2-year-old girl revealed a large mass filling the right hemithorax which was determined to be a type II PPB after pathological examination. Imaging of the 6-month-old sibling demonstrated a small cystic lesion in the posterior basal segment of the right lower lobe which was determined to be a type 1r PPB after pathological examination. The 2-year-old girl received adjuvant chemotherapy while the baby sister underwent resection alone and both are alive and well at 12 months and 7 months, respectively. Sequence analysis in both cases confirmed the sameDICER1variation, c.2437-2A>G (likely pathogenic), which has not been previously described in the literature.

Rationale Signet-ring cell is a rare morphological finding in bone marrow, which usually indicates metastatic carcinoma from either the gastrointestinal tract or a primary hematolymphoid neoplasm. Here, we present a very unusual case of lobular breast carcinoma with metastasis to the bone marrow. Patient concerns A 67-year-old female with estrogen receptor (ER)-positive lobular breast carcinoma was staged as T3N3M0, and treated with modified radical mastectomy followed by chemotherapy and radiotherapy. One year after treatment, she was noted to have moderate thrombocytopenia on complete blood count with the remainder of the parameters within normal limits. Radiographic examination revealed no evidence of recurrent disease. Diagnosis Bone marrow biopsy was performed to exclude therapy-related myelodysplastic syndrome (MDS), which demonstrated hypercellularity with "hyperplastic" hematopoiesis. Upon closer inspection, a few signet-ring cells were identified which morphologically resembled histiocytes. These formed an interstitial infiltrate among the predominantly hematopoietic elements, and could have been easily overlooked. Immunohistochemistry demonstrated that these signet-ring cells were positive for pancytokeratin as well as ER which confirmed metastatic lobular breast carcinoma. On retrospective review of the aspirate smear, rare signet-ring cells were identified. Interventions The patient was treated with additional chemotherapy. Outcomes The patient eventually succumbed to overt dissemination after 14 months. Lessons Due to the relative discohesiveness of lobular breast carcinoma, the cells frequently assume single-cell infiltration in bone marrow. This attribute, along with small cell size, bland cytologic features and paucity of tissue response, contributes to its escaping from identification on hematoxylin-eosin (H&E) sections. In this case, the signet-ring cells were hidden in apparently hyperplastic hematopoiesis. Careful inspection raised the possibility of occult metastasis which was readily detected and confirmed with immunohistochemistry.

The heat shock response (HSR) is responsible for maintaining cellular and organismal health through the regulation of proteostasis. Recent data demonstrating that the mammalian HSR is regulated by SIRT1 suggest that this response may be under metabolic control. To test this hypothesis, we have determined the effect of caloric restriction in Caenorhabditis elegans on activation of the HSR and have found a synergistic effect on the induction of hsp70 gene expression. The homolog of mammalian SIRT1 in C. elegans is Sir2.1. Using a mutated C. elegans strain with a sir2.1 deletion, we show that heat shock and caloric restriction cooperate to promote increased survivability and fitness in a sir2.1-dependent manner. Finally, we show that caloric restriction increases the ability of heat shock to preserve movement in a polyglutamine toxicity neurodegenerative disease model and that this effect is dependent on sir2.1.