Primary epithelioid angiosarcoma of endometrium.

Angiosarcoma is a poor prognostic tumor observed less than 1% in soft tissue, while it is rarely detected in the endometrium and has been described in few case reports. In this report, we present a case of primary epithelioid angiosarcoma of endometrium to raise awareness and emphasize for pathologists and clinicians.

Relevance of Additional Immunohistochemical Markers in the Differential Diagnosis of Small B-Cell Lymphomas: A Case-Control Study

Objective: Clinical and pathological differential diagnosis of small B-cell lymphomas (SBCLs) is still controversial and may be difficult due to their overlapping morphology, phenotype, and differentiation to plasma cells. We aimed to examine the expression of the immune receptor translocation-associated protein 1 (IRTA1), myeloid cell nuclear differentiation antigen (MNDA), lymphoid enhancer-binding factor-1 (LEF1), and stathmin 1 (STMN1) markers in SBCL cases involving different sites that may have plasma cell differentiation. Materials and Methods: We studied 154 tissue samples with lymphoma involvement from 116 patients and evaluated the staining distribution of the markers. Expressions were evaluated in 21 chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), 7 follicular lymphoma (FL), 14 nodal marginal zone lymphoma, 17 extranodal marginal zone lymphoma, 55 splenic marginal zone lymphoma, 22 marginal zone lymphoma-not otherwise specified, and 18 lymphoplasmacytic lymphoma/Waldenström macroglobulinemia cases by immunohistochemistry. Results: The results confirmed that LEF1 was the most sensitive and specific marker for CLL/SLL and STMN1 was the most sensitive and specific marker for FL (p<0.001). MNDA and IRTA1 were useful markers to distinguish marginal zone lymphomas. Conclusion: Our results suggest that LEF1 for CLL/SLL and STMN1 for FL are reliable markers. LEF1, MNDA, STMN1, and IRTA1 are helpful with other routinely used immunohistochemical markers in a diagnostic algorithm considering their limitations.

Superficial Acral Fibromyxoma.

Superficial acral fibromyxoma is a rare, benign, slow-growing, soft-tissue tumor commonly located in the acral regions, with a predilection for the great toe, developing from the nail unit. Because of its nonspecific features and rarity, clinical diagnosis is difficult. In this article, we present a case of superficial acral fibromyxoma located in the nail unit with new dermatoscopic and radiologic findings that have not been previously reported in the literature.

A Novel PUS1 Mutation in 2 Siblings with MLASA Syndrome: A Review of the Literature.

ABSTRACT: Myopathy, lactic acidosis, and sideroblastic anemia (MLASA) is a rare mitochondrial disorder characterized by MLASA. Variable features of this condition include failure to thrive, and developmental delay or intellectual disability. Additional symptoms consist of cognitive impairment, skeletal and dental abnormalities, delayed motor milestones, cardiomyopathy, dysphagia, and respiratory insufficiency. MLASA has previously been associated with mutations in pseudouridylate synthase 1 (PUS1) and YARS2. PUS1 encodes the nuclear PUS1 enzyme, which is located in both the nucleus and the mitochondria. PUS1 converts uridine into pseudouridine in several cytosolic and mitochondrial transfer RNA positions and increases the efficiency of protein synthesis in both compartments.In the present report, we report on 2 Turkish sisters 4 and 11 of years with an MLASA plus phenotype. Both patients have sideroblastic anemia, lactic acidosis, failure to thrive, developmental delay, and chronic diarrhea; in addition, the older sister has strabismus and skeletal anomalies. The sequencing of the PUS1 gene revealed a novel homozygous p.Glu311* mutation. The phenotype of the older sibling is also unique because of the strabismus and skeletal anomalies, when compared with her sister and other previously reported patients with MLASA. The structural differences in the nuclear versus mitochondrial isoforms of PUS1 and modifier genes may be implicated in the variability of the clinical presentations in MLASA. CONCLUSION: This report adds to the growing number of mutations causing complex clinical manifestations of MLASA including lactic acidosis, sideroblastic anemia, chronic diarrhea, and myopathy.

Diagnostic importance of clinicopathologic features and p16, CD34, MDM2 expression in differential diagnosis of adipocytic tumors.

OBJECTIVE: The aim of this study was to investigate the immunohistochemical stain profiling of adipocytic tumors. METHODS: From our archive files between the years of 2012-2018, excised, formalin-fixed and paraffin-embedded adipocytic tumors were retrospectively screened and 61 subjects were selected. The gender, age, tumor location and tumor diameter were evaluated. The cases were investigated in terms of p16, CD34, MDM2 expression and clinicopathological information. RESULTS: Of the 61 patients included in the study, we found that 2 had hibernoma, 4 had lipoblastoma, 14 had spindle cell lipoma (SCL), 10 had lipoma, 20 had atypical lipomatous tumor/well differentiated liposarcoma (ALT/WDL), and 11 had dedifferentiated liposarcoma (DDL). In terms of diameter, ALT/WDL and DDL were significantly different from the others (p=0.001, p=0.001, respectively). There was a significant difference between the groups according to the location (p=0.001). 35% (7/20) of ALT/WDLs were in the lower extremities (thighs) and 35% (7/20) were located in the retroperitoneal region. 70% of DDLs (7/11) were located in the retroperitoneum. When CD34 expression was evaluated among the groups, a significant difference was observed (p=0.001). CD34 was positive in 92.9% of SCL cases. p16 immunoreactivity was significantly different between the groups (p=0.001). p16 expression was observed in 50.5% of ALT / WDL cases and 79% of DDL cases. CONCLUSION: p16 and CD34 expression are valuable in the differential diagnosis of lipomatous tumors when radiological and clinical considerations do not help to differential diagnosis of adipocytic tumors. LEVEL OF EVIDENCE: Level IV, Therapeutic Study.

The prognostic importance of TGF-ß, TGF-ß receptor, and fascin in childhood solid tumors.

Fascin plays a role in tumor metastasis under the influence of TGF-ß, each potentiating the effect of the other. We retrospectively investigated whether there was a prognostic relationship between TGF-ß and fascin, and disease stage, local recurrence, metastasis tendency, and response to treatment. Twelve neuroblastomas, 17 osteosarcomas, 14 Ewing's sarcomas, 15 rhabdomyosarcoma cases, and 8 rare solid tumors were included. Serum TGF-ß levels were high at the time of diagnosis in all groups (p = .015) and decreased significantly during remission (p = .008). Serum TGF-ß values in the relapse period rarely reached high levels at the time of diagnosis and even stayed under the control group values (p = .017). When TGF-ß receptor expression in tumor tissues was evaluated, the association of TGF-ß receptor positivity with metastatic disease and advanced stage was striking. We found that 88% of rhabdomyosarcoma cases with alveolar histopathology expressed the TGF-ß receptor, and the association between TGF-ß receptor positivity and alveolar histopathology seemed to be a negative prognostic marker. When fascin levels were evaluated in childhood solid tumor tissue, the risk of relapse increased when the fascin total score at diagnosis was >4. This is one of the few studies including prognostic markers such as serum TGF-ß, tissue TGF-ß, TGF-ß receptor, and fascin in pediatric solid tumors. Considering the poor prognosis of advanced stage pediatric solid tumors and the need for biomarkers to predict which patient might need more intensive therapy or warrant closer follow-up afterward, we think that TGF-ß, TGF-ß receptor, and fascin expression have an important prognostic role.

Bilaterally Diffuse Lacrimal Gland Involvement: Initial Presentation of Systemic Sarcoidosis.

Orbital involvement in systemic sarcoidosis is a rare condition. We report a case of orbital sarcoidosis with bilaterally huge lacrimal gland involvement as the initial manifestation of systemic sarcoidosis. A 20-year-old woman admitted the ophthalmology department with progressive bilateral upper eyelid swelling for 6 months. The only pathologic finding was the presence of bilateral, symmetrical, solid, lobular masses at the lateral upper eyelids at the location of lacrimal glands. On systemic examination, bilateral parotid and submandibular glands appeared swollen. Magnetic resonance imaging of the orbit revealed bilateral symmetrical diffuse enlargement of the lacrimal glands with maximum and minimum thickness of 11 mm and 7 mm, respectively. The biopsy findings were compatible with sarcoidosis. Although lacrimal gland involvement has been reported in different studies, we for the first time report an unusual case with bilateral diffuse huge lacrimal gland involvement. Normal lacrimal gland thickness is approximately 4-5 mm in magnetic resonance imaging, while our case had bilateral diffuse enlargement of lacrimal glands, which showed maximum and minimum thickness of 11 mm and 7 mm, respectively. Although orbital involvement is uncommon in sarcoidosis, it should be remembered in the differential diagnosis of orbital masses.

Clinical and pathological characteristics of gastrointestinal stromal tumor (GIST) metastatic to bone.

Our aim in this study was to describe the clinical, morphological, and molecular profile of gastrointestinal stromal tumor (GIST) metastatic to bone. We analyzed the morphological, phenotypic, and molecular characteristics of seven cases, and in addition reviewed 17 cases from literature. Sequence analysis of KIT and PDGFRA genes was possible for six cases. For the GIST cases with bone metastasis, the most common primaries were small intestine (29%), stomach (25%), and rectum (21%). Sites of bone metastases were vertebrae (11), pelvis (8), femur (8), ribs (6), humerus (5), skull (3), scapula (1), and mandible (1). The size ranged from 1.5 to 13 cm (median, 3.8 cm). Bone metastases without involvement of any other organ were seen in 17% of the cases and were solitary in 14 (58%). Adjacent soft tissue involvement was present in nearly half of the patients. Bone metastasis was either manifest at the time of diagnosis (28%) or occurred after a mean period of 4.7 years (3 months-20 years). Morphologically, neoplastic cells were spindle in 67%, epithelioid in 13%, and mixed epithelioid and spindle in 20%. CD117, DOG1, and CD34 were positive in 88, 86, and 85% of the cases, respectively. KIT Exon 11 mutations were the most frequent gene alteration (78%), followed by KIT Exon 13 mutations. Of 17 of the cases with available follow-up information, 7 (41%) patients developed bone metastasis under imatinib therapy. Five patients (29%) died of disease within a mean of 17 months. Bone metastases from GIST are usually found in patients with advanced disease and typically present as lytic masses with occasional soft tissue involvement. We could not identify any KIT or PDGFRA alterations predisposing to bone metastasis.

Retroauricular Approach for Targeted Cochlear Therapy Experiments in Wistar Albino Rats.

BACKGROUND: As the idea of stem cell technology in the treatment of sensorial hearing loss has emerged over the past decades, the need for in vivo models for related experiments has become explicit. One of the most common experimental models for inner ear stem cell delivery experiments is the Wistar albino rat. AIMS: To investigate the surgical anatomy of the temporal bone of the Wistar albino rat with respect to the dissection steps, operative techniques and potential pitfalls of surgery. STUDY DESIGN: Animal experimentation. METHODS: Adult Wistar albino rats were operated on via the retroauricular approach under an operation microscope. The anatomy of the temporal bone, the surgical route to the temporal bulla and the inner ear were investigated. Technical details of surgical steps, complications and potential pitfalls during the surgery were noted. RESULTS: The study group consisted of 40 adult Wistar albino rats. The mean times to reach the bulla and to achieve cochleostomy were 4.3 (2-13 min) and 7.5 min (3.5-22 min), respectively. The mean width of the facial nerve was 0.84 mm (0.42-1.25 mm). The stapedial artery lay nearly perpendicular to the course of the facial nerve (88-93 °C). There were three major complications: two large cochleostomies and one massive bleed from the stapedial artery. CONCLUSION: The facial nerve was the key anatomical landmark in locating the bulla. By retrograde tracing of the facial nerve, it was possible to find the bulla ventral (inferior) to the main trunk. The facial nerve trunk was the upper limit when drilling the bulla. By dissecting the main trunk of the facial nerve and retracting cranially, a large drilling space could be achieved. Our results suggest that the retroauricular approach is an effective, feasible route for inner ear drug delivery experiments in Wistar albino rats.

[B-cell non-Hodgkin's lymphoma with the involvement of inferior turbinate: a case report]. / Alt konka tutulumu gösteren B-hücreli non-Hodgkin lenfoma: Olgu sunumu.

The non-Hodgkin's lymphoma is a significant malignant disease that can involve in the extranodal region of the head and neck. It does not show any specific symptoms when it resides in this region. Swelling, pain and ulceration are important clinical findings. In this article, we report a 57-year-old male patient diagnosed with B cell non-Hodgkin's lymphoma by histopathologic examination, who had nasal blockage, snoring and headache complaints for one year, whose endoscopic nasal examination revealed a mass arising from the right inferior turbinate and the mass was removed surgically by endoscopic approach.

Study of mouse induced pluripotent stem cell transplantation intoWistar albino rat cochleae after hair cell damage.

BACKGROUND/AIM: As the regeneration capacity of hair cells is limited, inner ear stem cell therapies hold promise. Effects of mouse induced pluripotent stem cells (IPSCs) on Wistar albino rats (WARs) with hearing impairment were investigated. MATERIALS AND METHODS: Thirty-five adult WARs with normal hearing were divided into 4 groups. Excluding the study group (n = 15), the other three groups served as control groups for ototoxicity and IPSC injection models. IPSC injections were performed via cochleostomy after a retroauricular approach. Auditory functions were evaluated with auditory brainstem responses (ABRs) before and after the injections. After a final hearing assessment the WARs were sacrificed and cochleae were extracted to see the biologic behavior of IPSCs in the inner ear by light microscopy and immunohistochemistry. RESULTS: There were no significant differences in the click-ABR thresholds in the study group after IPSC transplantation. The mean hearing threshold in the study group after ototoxic agent injection was 53.2 dB (10-90 dB). There was no significant difference between groups (P > 0.05) and no differentiated stem cells were observed immunohistochemically. CONCLUSION: Transplanted IPSCs did not show a therapeutic effect in this trial. We discuss potential pitfalls and factors affecting the therapeutic effect.

Diffuse Large B-Cell Lymphoma Presenting with Bilateral Renal Masses and Hematuria: A Case Report.

Renal involvement is most often seen in conjunction with multisystemic, disseminated lymphoma either by direct extension from a retroperitoneal mass or via hematogenous spread. Primary lymphoma of the kidney is not a common entity and it is a controversial issue on account of the absence of lymphatic tissues in the normal kidney. In this case report, we describe a 19-year-old male with hematuria, acute kidney injury, and bilateral renal masses due to massive lymphomatous infiltration of the kidneys, which was diagnosed as diffuse large B-cell non-Hodgkin lymphoma by Tru-Cut biopsy.

Myeloid sarcomas: a clinicopathologic study of 20 cases.

OBJECTIVE: Myeloid sarcoma is a tumoral mass of mature or immature myeloid blasts in extramedullary anatomic locations. It can be seen de novo or in association with acute myeloid leukemia, myeloproliferative neoplasias, or myelodysplastic syndrome. Isolated myeloid sarcoma can be seen as a relapse in cases with allogenic bone marrow transplantation. Although it may involve any tissue in the body, the most common locations are skin, soft tissues, lymph nodes, and the gastrointestinal tract. Immunohistochemically, most cases show myelomonocytic or pure monoblastic differentiation. We reviewed the clinicopathological features of 20 cases of myeloid sarcoma diagnosed in our institute in view of the literature. MATERIALS AND METHODS: The cases diagnosed between 2005 and 2012 at the Ankara University Faculty of Medicine, Department of Pathology, were selected. Clinicopathological findings including the age and sex of the patients; symptoms; anatomic location; accompanying hematological disease; and the morphological, immunohistochemical, and cytogenetic features of the cases were noted. RESULTS: Sixteen of the patients were male and 4 were female. The median age at diagnosis was 47 years. The most commonly involved locations were the lymph nodes and skin. Immunohistochemically, eleven cases were of the myelomonocytic and 7 cases were of the myeloid phenotype, whereas 2 cases showed pure monoblastic differentiation. The median follow-up period for the 18 cases with known clinical data was 33 weeks. Five patients died of the disease in an average of 36 weeks. CONCLUSION: Myeloid sarcoma is a rare presentation of leukemias, myeloproliferative neoplasias, or myelodysplastic syndrome, composed of immature myelomonocytic cells in extramedullary tissues. It may present with variable morphological and phenotypic features, always creating a challenge in pathological diagnosis.

Epstein-barr virus-negative post-transplant lymphoproliferative diseases: three distinct cases from a single center.

Three cases of Epstein-Barr virus (EBV)-negative post-transplant lymphoproliferative disease that occurred 6 to 8 years after renal transplantation are reported. The patients respectively had gastric mucosa-associated lymphoid tissue lymphoma, gastric diffuse large B-cell lymphoma, and atypical Burkitt lymphoma. Absence of EBV in the tissue samples was demonstrated by both in situ hybridization for EBV early RNA and polymerase chain reaction for EBV DNA. Patients were treated with reduction in immunosuppression and combined chemotherapy plus an anti-CD20 monoclonal antibody, rituximab. Despite the reduction in immunosuppression, patients had stable renal functions without loss of graft functions. The patient with atypical Burkitt lymphoma had an abnormal karyotype, did not respond to treatment completely, and died due to disease progression. The other patients are still alive and in remission 5 and 3 years after diagnosis, respectively. EBV-negative post-transplant lymphoproliferative diseases are usually late-onset and are reported to have poor prognosis. Thus, reduction in immunosuppression is usually not sufficient for treatment and more aggressive approaches like rituximab with combined chemotherapy are required.

Diagnosis of large granular lymphocytic leukemia in a patient previously treated for acute myeloblastic leukemia.

Large granular lymphocytic (LGL) leukemia is a lymphoproliferative disease characterized by the clonal expansion of cytotoxic T or natural killer cells. We report on a patient diagnosed with T-cell LGL leukemia two years after the achievement of hematologic remission for acute myeloblastic leukemia.

Miliary brain metastases from occult lung adenocarcinoma: Radiologic and histopathologic confirmation.

"Miliary brain metastases", also termed as "Carcinomatous encephalitis", are an extremely rare form of cerebral metastasis. Here in this article, we report a 52 year-old male patient with miliary brain metastases originating from occult lung adenocarcinoma. There were no significant findings on his initial physical and neurological examinations except limited cooperation. Brain computed tomography revealed edematous regions at the inferior sections of both parietal lobes. Then after, the contrast-enhanced magnetic resonance imaging revealed innumerable multi-dimensional lesions associated with surrounding edema on T2-weighted images. The proton magnetic resonance spectroscopy revealed increases in the choline and lipid peaks with decreased N-acetylaspartate in a similar manner with metastatic brain tumors. Histopathological findings pointed out that malignant epithelial tumor metastasis were originating in primary lung adenocarcinoma. Despite the advances in technical equipments and medical knowledge, miliary metastatic brain tumors are quite rare and the differential diagnosis is difficult. Our aim in this article was to present this rare case in which the lung was thought to be the primary focus; and outline the radiological characteristics. Also, we believe that the findings presented by proton magnetic resonance spectroscopy may contribute to making a differential diagnosis.

Endometriose cutânea / Cutaneous endometriosis

A endometriose é definida como a presença de glândulas endometriais e estroma fora da cavidade uterina. Essa doença, comum nas mulheres, é geralmente observada durante os anos reprodutivos. Embora a pelve seja o sítio mais comum da endometriose em mulheres, a localização extrapélvica é menos frequente e ainda mais difícil de diagnosticar, em decorrência das apresentações distintas. Neste artigo é descrito um caso de endometriose de cicatriz da parede abdominal.

Endometriosis is defined as the presence of endometrial glands and stroma outside the uterine cavity. This disease is commonly observed in women, particularly those of reproductive age. The pelvis is the most common location for endometriosis. On the other hand, extrapelvic endometriosis, which is less common, is more difficult to diagnose because of the extreme differences in its presentation. In this article, we describe our experience of a case of endometriosis in an abdominal wall scar.

Intra-articular epithelioid sarcoma showing mixed classic and proximal-type features: report of 2 cases, with immunohistochemical and molecular cytogenetic INI-1 study.

Epithelioid sarcoma, a rare sarcoma with epithelial differentiation, most often occurs in the distal extremities; however, it may occur in essentially any location. With the recent recognition that the loss of expression of the tumor-suppressor gene INI-1 may be associated with epithelioid sarcoma, it has become clear that epithelioid sarcoma may occur in previously unsuspected locations such as bone. Only 2 cases of intra-articular epithelioid sarcoma have been previously reported. We retrieved 2 intra-articular cases coded as epithelioid sarcoma from our archives. Both expressed cytokeratins (AE1/AE3 and OSCAR), CD34, vimentin, and epithelial membrane antigen, and showed complete loss of expression of INI-1. Fluorescence in situ hybridization was performed on formalin-fixed, paraffin-embedded sections by using a laboratory-developed dual-color probe containing INI1 (CTD-2511E13 and CTD-2034E7) (22q11.2) (OR) and PANX2 (RPCI3-402G11) (22q13.33) (GR) probes as control. Both cases occurred in a clearly intra-articular location in the knee. Case 1 was that of a 19-year-old man with a long-standing history of pain and limited joint function. This patient was disease free after amputation. Case 2 was that of a 60-year-old woman. Follow-up information available for this patient showed bilateral subpleural metastases. Morphologically, case 1 showed features of proximal-type epithelioid sarcoma, whereas case 2 showed mixed features of classic and proximal-type epithelioid sarcoma. Immunohistochemistry showed complete loss of INI-1 protein in both cases; fluorescence in situ hybridization analyses were negative for INI-1 gene deletion. Herein, we have reported 2 cases of intra-articular epithelioid sarcoma, showing morphologic and immunohistochemical features identical to those of epithelioid sarcoma in conventional locations, including loss of INI-1 expression. Intra-articular epithelioid sarcoma should be distinguished from malignant pigmented villonodular synovitis and from carcinoma metastatic to the synovium. Improved recognition of this rare clinical presentation should allow for better understanding of its unique features.