Cutaneous leiomyosarcoma: a retrospective review of 45 cases.

Primary cutaneous leiomyosarcoma (LMS) is a rare soft tissue tumour type with two subtypes, dermal and subcutaneous. As deeper tumours confer a worse prognosis, they require a more aggressive approach. Conversely, a more conservative surgical approach for dermal LMS has been suggested. Few studies have comprehensively reported both clinical surgical and histological excision margins. Therefore, we sought to provide margin recommendations based on our experience and review of the existing literature. We undertook a retrospective case-note review (1998-2019) of cutaneous LMS management to establish histological/surgical margins using pathology/electronic patient records. The diagnosis was made and classified by an experienced dermatopathologist according to the World Health Organization classification. In the dermal LMS cohort (n = 35), mean peripheral and deep histological margins were 5.4 mm (range 0.5-20) and 5.6 mm (range 0.1-14.5), respectively. The incomplete excision rate was 31% (11 of 35). There were no recurrences. In the subcutaneous LMS cohort (n = 10), mean peripheral and deep histological margins were 5.7 mm (range 0.2-14) and 1.1 mm (range 0.2-1.7), respectively. The incomplete excision rate was 40% (4 of 10). The recurrence rate was 20% (2 of 10) despite achieving histological clearance after 1 year. One lung metastasis occurred 1 year following an adequately excised primary scalp LMS. Thus, for dermal LMS we propose a clinical margin of 5-10 mm (depending on lesion size) at the initial excision or at scar re-excision following involved/close histological peripheral and/or deep margins (i.e. < 1 mm). For subcutaneous LMS, we suggest a clinical margin of 15-20 mm (depending on lesion size) to achieve a peripheral histological clearance of 10 mm and negative deep margin (i.e. > 1 mm), down to the periosteum/fascia/muscle according to anatomical site. If this is not achieved, a re-excision would be recommended. However, prospective studies are needed for optimal guidance.

Metal distribution, bioavailability and isotope variations in polluted soils from Lower Swansea Valley, UK.

Soils in the Lower Swansea Valley, (United Kingdom) contain elevated level of metals, enough to cause direct or indirect effects on human health. This study assesses the severity of soil pollution and bioavailability of Cu and other metals (Ni, Zn, Co, Pb and Cr) in soils with various distances from a Ni refinery. We compare Cu concentrations in operationally defined soil fractions (bioavailable, bound to Fe/Mn oxide and incorporated in organic matter) with other metals (Ni, Zn, Pb, Co, Cr) usually occurring in ores used in metallurgic processes and report their pollution and geoaccumulation indices (PI and Igeo). Further, we use Cu stable isotope ratios (δ65Cu) to trace the fate and mobility of Cu in soils. Our data suggest a point source of contamination for some of the heavy metals including Ni (Igeo = 1.9), Zn (Igeo = 0.28) and Cu (Igeo = 3.6) near the Ni refinery. However, Co (Igeo = 0.15) and Pb (Igeo = 3.3) contaminations are likely to be linked to different sources. No elevated Cr levels (Igeo= -0.07) occur in any of the studied soils. All soil metals are predominantly associated with organic matter (>50%) which  reduces their bioavailibility and thus their risk for ecological and human health. The Cu isotope data show that Cu in soil organic matter is enriched in 65Cu, while the lighter isotopes (63Cu) remain in the dissolved bioavailable Cu fraction (Δ65Cuorganic-bioavailable is +0.12 ± 0.13‰). This suggests the preferential complexation of 65Cu with soil organic matter after dissolution of Cu deposited to the soil. Thus, Cu isotope data can effectively indicate pathways of metal migration in polluted soils.

Case Report of IgM Multiple Myeloma: Diagnosing a Rare Hematologic Entity.

IgM multiple myeloma is an exceedingly rare hematologic entity comprising only less than 0.5% of multiple myeloma cases. Given the rarity of this disorder, it makes it a challenge to differentiate from other more prevalent hematologic disorders like Waldenstrom macroglobulinemia. These 2 diseases have the common finding of an IgM monoclonal gammopathy and distinguishing between these 2 diagnoses is of great importance given that therapy and prognosis differ significantly. This report illustrates the case of a 64-year-old man who presented with IgM lambda monoclonal gammopathy in whom signs, symptoms, laboratories, and imaging were initially thought to be consistent with Waldenstrom macroglobulinemia. Upon further analysis, which included bone marrow biopsy, flow cytometry, immunohistochemistry, fluorescence in situ hybridization, and MYD88 (L265P) gene mutation analysis, the rare diagnosis of IgM multiple myeloma was confirmed. As highlighted by this patient's case, reaching the diagnosis of IgM multiple myeloma can be a difficult task which requires a high index of suspicion and accurate diagnostic methods. By using the approach detailed in this report, more cases of IgM multiple myeloma can be diagnosed early, which in turn may lead to earlier treatment and better outcomes.

The Examination of Patient-Reported Outcomes and Postural Control Measures in Patients With and Without a History of ACL Reconstruction: A Case Control Study.

CONTEXT: There is a lack of literature to support the diagnostic accuracy and cut-off scores of commonly used patient-reported outcome measures (PROMs) and clinician-oriented outcomes such as postural-control assessments (PCAs) when treating post-ACL reconstruction (ACLR) patients. These scores could help tailor treatments, enhance patient-centered care and may identify individuals in need of additional rehabilitation. OBJECTIVE: To determine if differences in 4-PROMs and 3-PCAs exist between post-ACLR and healthy participants, and to determine the diagnostic accuracy and cut-off scores of these outcomes. DESIGN: Case control. SETTING: Laboratory. PARTICIPANTS: A total of 20 post-ACLR and 40 healthy control participants. MAIN OUTCOME MEASURES: The participants completed 4-PROMs (the Disablement in the Physically Active Scale [DPA], The Fear-Avoidance Belief Questionnaire [FABQ], the Knee Osteoarthritis Outcomes Score [KOOS] subscales, and the Tampa Scale of Kinesiophobia [TSK-11]) and 3-PCAs (the Balance Error Scoring System [BESS], the modified Star Excursion Balance Test [SEBT], and static balance on an instrumented force plate). Mann-Whitney U tests examined differences between groups. Receiver operating characteristic (ROC) curves were employed to determine sensitivity and specificity. The Area Under the Curve (AUC) was calculated to determine the diagnostic accuracy of each instrument. The Youdin Index was used to determine cut-off scores. Alpha was set a priori at P < 0.05. RESULTS: There were significant differences between groups for all PROMs (P < 0.05). There were no differences in PCAs between groups. The cut-off scores should be interpreted with caution for some instruments, as the scores may not be clinically applicable. CONCLUSIONS: Post-ACLR participants have decreased self-reported function and health-related quality of life. The PROMs are capable of discriminating between groups. Clinicians should consider using the cut-off scores in clinical practice. Further use of the instruments to examine detriments after completion of standard rehabilitation may be warranted.

Somatosensory deficits in post-ACL reconstruction patients: A case-control study.

INTRODUCTION: Diminished cutaneous detection thresholds have been identified in patients with multiple orthopedic conditions, and these phenomena may occur in postanterior cruciate ligament reconstructed (ACLR) patients. The purpose of this study was to determine if differences in lower extremity cutaneous detection thresholds exist in post-ACLR patients when compared with healthy controls. METHODS: Fifteen individuals who were post-ACLR and 15 individuals who had no history of knee injury participated. Light touch cutaneous detection thresholds were assessed at 4 locations on the foot and ankle (first metatarsal, fifth metatarsal, medial malleolus, and lateral malleolus). Nonparametric statistics examined group differences between the sites. RESULTS: ACLR subjects had decreased cutaneous sensation at the first metatarsal and medial malleolus compared with healthy controls. CONCLUSIONS: Somatosensory deficits are present in post-ACLR patients. Future research should investigate these phenomena longitudinally in post-ACLR individuals along with somatosensory targeted interventions. Muscle Nerve 55: 5-8, 2017.

Primary Adrenal Angiosarcoma: A Rare and Potentially Misdiagnosed Tumor.

A man aged 69 years presented with acute right flank pain secondary to a hemorrhagic large adrenal tumor. En bloc resection was performed to repair the inferior vena cava. Immunoperoxidase levels in the tumor were positive for factor VIII and CD31 and negative for S100, protein Melan-A, CD34, synaptophysin, chromogranin, desmin, muscle specific actin, ETFA (EMA), KRT20 (CK20), CDX2, TTF1, LNPEP (PLAP), inhibin, ?-fetoprotein, CD30, hepatocyte paraffin, and aberrant expression of cytokeratin 7 and pankeratin. The pathological diagnosis was consistent with adrenal angiosarcoma. Obtaining appropriate immunoperoxidase stains and multidisciplinary evaluation helped make the diagnosis of this rare adrenal tumor and determine its management. The patient had an uneventful postoperative course and completed 4 cycles of adjuvant chemotherapy with doxorubicin/ifosfamide and adequately tolerated the treatment. However, positive surgical margins were found, so he was referred to radiation oncology specialists for possible adjuvant radiotherapy to the surgical bed. Weeks after the first initiation of therapy, the patient presented to the emergency department complaining of shortness of breath, fatigue, and generalized weakness for 3 days. He was admitted and found to have new-onset anemia and a new-onset, large, right pleural effusion. Thoracentesis performed showed sanguinolent fluid that, after microscopic evaluation, was suggestive of recurrent malignancy. Thoracic aortography performed with subselective catheterization to several arteries (right bronchial, right phrenic, and right renal arteries) did not show any active bleeding. However, the right inferior intercostal and adrenal arteries were presumed to be the reason for the bleeding event, so they were embolized until stasis. The patient remained hemodynamically unstable but eventually experienced multiorgan failure. In spite of aggressive measures, he died 10 days after admission to the hospital.

Diagnosis of tumors during tissue-conserving surgery with integrated autofluorescence and Raman scattering microscopy.

Tissue-conserving surgery is used increasingly in cancer treatment. However, one of the main challenges in this type of surgery is the detection of tumor margins. Histopathology based on tissue sectioning and staining has been the gold standard for cancer diagnosis for more than a century. However, its use during tissue-conserving surgery is limited by time-consuming tissue preparation steps (1-2 h) and the diagnostic variability inherent in subjective image interpretation. Here, we demonstrate an integrated optical technique based on tissue autofluorescence imaging (high sensitivity and high speed but low specificity) and Raman scattering (high sensitivity and high specificity but low speed) that can overcome these limitations. Automated segmentation of autofluorescence images was used to select and prioritize the sampling points for Raman spectroscopy, which then was used to establish the diagnosis based on a spectral classification model (100% sensitivity, 92% specificity per spectrum). This automated sampling strategy allowed objective diagnosis of basal cell carcinoma in skin tissue samples excised during Mohs micrographic surgery faster than frozen section histopathology, and one or two orders of magnitude faster than previous techniques based on infrared or Raman microscopy. We also show that this technique can diagnose the presence or absence of tumors in unsectioned tissue layers, thus eliminating the need for tissue sectioning. This study demonstrates the potential of this technique to provide a rapid and objective intraoperative method to spare healthy tissue and reduce unnecessary surgery by determining whether tumor cells have been removed.

Lesson of the month 1: Seeing snowflakes.

Melanoma-associated retinopathy is a rare paraneoplastic complication of metastatic cutaneous malignant melanoma. It may present years after the original diagnosis of melanoma. We describe a patient with this condition who presented with persistent visual symptoms.

A Hispanic female patient with heartburn: A rare presentation of Paroxysmal Nocturnal Hemoglobinuria.

Paroxysmal nocturnal hemoglobinuria (PNH) is a non-malignant, acquired clonal hematopoietic stem cell disease that can present with bone marrow failure, hemolytic anemia, smooth muscle dystonias, and thrombosis. We present a case of a 32 year-old-female, G2P2A0 with no past medical history of any systemic illnesses who refers approximately 2 months of progressively worsening constant heartburn with associated abdominal discomfort. CBC showed leukopenia (WBC 2.9 x 103 /µL) with neutropenia (segmented neutrophils 48%), macrocytic anemia (Hgb 6.1 g/dL, hematocrit 20%, MCV,113 fL) and thrombocytopenia (platelet count 59 x 109/L). Abdomino-pelvic CT scan revealed a superior mesenterc vein thrombosis, which was treated initially with low-molecular-weight heparih for full anticoagulation. Peripheral blood flow cytometry assays revealed diminished expression of CD55 and CD59 on the erythrocytes, granulocytes and monocytes.' Paroxysmal nocturnal hemoglobinuria is a rare, clonal, hematopoietic stem-cell disorder whose manifestations are almost entirely explained by complement-mediated intravascular hemolysis. The natural history of PNH is highly variable, ranging from indolent to life-threatening. The median survival is 10 to 15 years, but with a wide range. Thrombosis is the leading cause of death, but others may die of complications of bone marrow failure, renal failure, myelodysplastic syndrome, and leukemia. Anticoagulation is only partially effective in preventing thrombosis in PNH; thus, thrombosis is an absolute indication for initiating treatment with Eculizumab. Nevertheless, bone marrow transplantation (BMT) is still the only curative therapy for PNH but is associated with significant morbidity and mortality.

Uncommon cause of life-threatening retroperitoneal hemorrhage in a healthy young Hispanic patient: splenic artery aneurysm rupture.

Splenic artery aneurysms (SAA) are a rare life threatening clinical diagnosis. We present a case of a young Hispanic woman with an aneurysm of the middle branch of the splenic artery and active leakage. The defect was embolized with complete resolution of the retroperitoneal bleeding. Physicians should be aware of this rare entity especially when female patients presents complainiing of severe epigastric pain with associated hypovolemic shock.

Surgical excision versus imiquimod 5% cream for nodular and superficial basal-cell carcinoma (SINS): a multicentre, non-inferiority, randomised controlled trial.

BACKGROUND: Basal-cell carcinoma is the most common form of skin cancer and its incidence is increasing worldwide. We aimed to assess the effectiveness of imiquimod cream versus surgical excision in patients with low-risk basal-cell carcinoma. METHODS: We did a multicentre, parallel-group, pragmatic, non-inferiority, randomised controlled trial at 12 centres in the UK, in which patients were recruited between June 19, 2003, and Feb 22, 2007, with 3 year follow-up from June 26, 2006, to May 26, 2010. Participants of any age were eligible if they had histologically confirmed primary nodular or superficial basal-cell carcinoma at low-risk sites. We excluded patients with morphoeic or recurrent basal-cell carcinoma and those with Gorlin syndrome. Participants were randomly assigned (1:1) via computer-generated blocked randomisation, stratified by centre and tumour type, to receive either imiquimod 5% cream once daily for 6 weeks (superficial) or 12 weeks (nodular), or surgical excision with a 4 mm margin. The randomisation sequence was concealed from study investigators. Because of the nature of the interventions, masking of participants was not possible and masking of outcome assessors was only partly possible. The trial statistician was masked to allocation until all analyses had been done. The primary outcome was the proportion of participants with clinical success, defined as absence of initial treatment failure or signs of recurrence at 3 years from start of treatment. We used a prespecified non-inferiority margin of a relative risk (RR) of 0.87. Analysis was by a modified intention-to-treat population and per protocol. This study is registered as an International Standard Randomised Controlled Trial (ISRCTN48755084), and with ClinicalTrials.gov, number NCT00066872. FINDINGS: 501 participants were randomly assigned to the imiquimod group (n=254) or the surgical excision group (n=247). At year 3, 401 (80%) patients were included in the modified intention-to-treat group. At 3 years, 178 (84%) of 213 participants in the imiquimod group were treated successfully compared with 185 (98%) of 188 participants in the surgery group (RR 0.84, 98% CI 0.78-0.91; p<0.0001). No clear difference was noted between groups in patient-assessed cosmetic outcomes. The most common adverse events were itching (211 patients in the imiquimod group vs 129 in the surgery group) and weeping (160 vs 81). We recorded serious adverse events in 99 (40%) of 249 participants in the imiquimod group and 97 (42%) of 229 in the surgery group had serious adverse events, but none were regarded as related to treatment. 12 (5%) participants in the imiquimod group withdrew because of adverse events compared with four (2%) in the surgery group. INTERPRETATION: Imiquimod was inferior to surgery according to our predefined non-inferiority criterion. Although excisional surgery remains the best treatment for low-risk basal-cell carcinoma, imiquimod cream might still be a useful treatment option for small low-risk superficial or nodular basal-cell carcinoma dependent on factors such as patient preference, size and site of the lesion, and whether the patient has more than one lesion. FUNDING: Cancer Research UK.

Bilateral large palpable cervical masses: not always a malignant or infectious process.

Madelung's disease is an extremely rare disorder of unknown etiology characterized by multiple, non-encapsulated, infiltrative lipomas located symmetrically on the trunk, neck, and proximal parts of the limbs. Approximately 200 patients have been reported in the medical literature. In this case report we present an extremely unusual case of multiple symmetric lipomatosis compatible with Madelung's disease.

A VERY RARE NEOPLASM IN AN IMMUNOCOMPETENT PATIENT.

Kaposi's sarcoma is a rare malignancy requiring infection with human Herpes virus for development. We report a case of a 76-year-old immunocompetent male with recurrent leg cellulitis. The cellulitis eventually developed into a non-healing ulcer and a palpable nodule consistent with nodular Kaposi's sarcoma.

Longitudinal, mixed method study to look at the experiences and knowledge of non melanoma skin cancer from diagnosis to one year.

BACKGROUND: Skin cancer is the most common type of cancer in humans and the incidence is increasing worldwide. Our objective was to understanding the needs, experiences and knowledge of individuals with Non Melanoma Skin Cancer (NMSC) from diagnosis up until one year. METHODS: Patients with NMSC completed questionnaires at diagnosis, treatment, 8 weeks post treatment and 12 months post diagnosis. Body image, psychological morbidity and Quality of Life (QOL) were assessed at each time point, with the exception of QOL that was not assessed at diagnosis. Knowledge of NMSC was assessed at baseline and 8 weeks. A sub-sample of participants was also interviewed to allow a more in-depth exploration of patients' experiences. RESULTS: 76 participants completed the initial questionnaire, of which 15 were interviewed. Patients were anxious about a diagnosis of skin cancer, however they were no more depressed or anxious than the general population. QOL significantly improved from diagnosis to 8 weeks and from diagnosis to one year. Knowledge of NMSC was poor and did not improve after treatment. Hairdressers were highlighted as playing an important role in raising awareness and encouraging individuals to seek medical help. Most participants were aware of the need to check their skin for suspicious lesions but were not sure what to look for. At one year participants had forgotten their experience and were not overly concerned about skin cancer. CONCLUSION: There is a need to raise awareness of the signs and symptoms of NMSC. Information on skin cancer needs to be tailored to the individual both at the start of treatment and during the follow up months, ensuring that participants' needs and expectations are met. Targeting education at individuals in the community who regularly come into contact with skin should help in early identification of NMSC. This is important since skin cancer caught early is easily treatable and delay in presentation leads to larger and more complex lesions which impacts in terms of increased morbidity and increased health care costs.

Small cell neuroendocrine carcinoma of rectum with associated paraneoplastic syndrome: a case report.

Neuroendocrine carcinomas of the colon and rectum comprise fewer than 1% of all colorectal cancers. These aggressive tumors generally have a poor prognosis compared to that associated with colorectal adenocarcinoma. We describe herein the case of a 68-year-old female presenting with a bleeding rectal mass involving the anal canal, which case was associated with hyponatremia due to inappropriate serum levels of antidiuretic hormone. The histopathological examination was consistent with a small-cell neuroendocrine tumor. She was treated with combination chemotherapy and radiation therapy. The Syndrome of Inappropriate Antidiuretic Hormone (SIADH) was managed with vasopressin antagonists. After the completion of therapy, endoscopic ultrasound revealed evidence of residual disease, for which she underwent an abdominoperineal resection (APR). The patient died 4 months later of disease progression. To our knowledge, this is the first report of a small-cell neuroendocrine tumor involving the rectum and anal canal that presented with the paraneoplastic syndrome, SIADH.

An Unexpected Presentation of a Maxillary Non-Hodgkin Lymphoma in an Elderly Hispanic Patient.

Extranodal NK/T-cell lymphoma (ENKTL), nasal type and aggressive NK cell leukemia are rare in Western World been less than 1% in USA to 8% in Asia among Non-Hodgkin's lymphomas. It is aggressive, with poor outcome and optimal treatment is unclear. A combination therapy that includes Peg-Asparaginase (SMILE) has been employed in young patients. An 85-year-old Puerto Rican male presented with anorexia, epistaxis, vertigo and involuntary facial movements. He was treated with injectable Onabotulinum toxin A due to suspicion of a hemifacial spasm. However, a CT scan demonstrated a left maxillary sinus lesion extending into the left middle turbinate with biopsy consistent with ENKTL. We adjusted therapy to patient's age and performance receiving Gemcitabine-Oxaliplatin (Gemox) with radiation obtaining a complete response with persistent negative Epstein Barr DNA titers. ENKTL is a rare disease initially misdiagnosed in our elderly patient, who demonstrated adequate response with a modified therapeutic regime.

Metastatic lymphoepithelioma to the orbit: an aggressive rare nasopharygeal tumor in a Hispanic patient.

A 64 year-old Hispanic male patient presented to our institution with a three-month history of frontal headaches, reduced vision, retroorbital pain, photophobia, sinus congestion, bloody nasal discharge, and decreased audition in the left ear. The diagnosis of metastatic lymphoepithelioma to the orbit was made based on clinical history, histopathological examination of an orbital biopsy, and imaging studies. Lymphoepithelioma rarely develops in Hispanic populations. However, it is endemic in certain areas, including North Africa, Southeast Asia. China and the far north hemisphere. Radiotherapy is th treatment of choice of localized lymphoepithelioma and concurrent chemotherapy-radiotherapy with neoadjuvant chemotherapy has been used in locally advanced metastatic settings.

Secondary biliary cirrhosis due to a rare choledochal cyst type II complicated with portal hypertension and pancytopenia in a young female patient.

Choledochal cyst type II, is an extremely rare cause of portal hypertension, severe pancytopenia in an adult patient, and a complication of long-standing disease. We present an uncommon cause of portal hypertension in a young female patient secondary to an obstructive choledochal cyst type II provoking massive splenomegaly and severe pancytopenia. A high level of clinical suspicion is important due to its high mortality rate if it remains undiagnosed. To our knowledge there are few publications describing this rare type of choledochal cyst in a Hispanic adult.