Primary Cutaneous Alveolar Rhabdomyosarcoma in an Elderly Adult: A Rare Potential Mimic of Merkel Cell Carcinoma.

ABSTRACT: Rhabdomyosarcoma (RMS) rarely arises as a primary skin tumor. It is also very rare in older adults, especially the alveolar type. We report an 80-year-old White woman who presented with a painful, erythematous, raised lesion (2 × 3.5 cm) above the left knee that was fixed within the skin, yet mobile about underlying soft tissue. A punch biopsy showed monotonous malignant round blue cells involving the dermis. Immunostains showed diffuse expression of CD56, focal chromogranin, focal dot-like pancytokeratin, CK7, and neurofilament, but negative for synaptophysin, CK20, SOX-10, MUM-1, CD43, TTF-1, and CD99. A CK20-negative variant of Merkel cell carcinoma was initially favored, but given the unusual immunophenotype and the presence of cellular dyscohesion, desmin and myogenin stains were performed, both of which were diffusely positive. Molecular testing revealed rearrangement of PAX3 and FOXO1 loci, confirming the diagnosis of alveolar RMS. PET/CT showed a probable 1.9-cm left inguinal lymph node metastasis; no internal or deep soft tissue primary tumor mass was identified, supporting a true primary cutaneous origin. Alveolar RMS may express keratins and neuroendocrine markers, making it easy to confuse with Merkel cell carcinoma on those exceptionally rare instances, when it arises in the skin of older adults.

Rabdomiosarcoma del ala nasal en un paciente pediátrico. Un reporte de caso / Nasal ala Alveolar Rhabdomyosarcoma in a pediatric patient. A rare case report

Dada la respiración nasal preferencial que tiene la población pediátrica en los primeros meses de vida, la obstrucción nasal tiene más repercusiones a nivel clínico a diferencia de un adulto, lo cual hace más prioritario su diagnóstico y manejo. Una de las principales causas de obstrucción nasal en niños son las masas nasales, las cuales debido a sus múltiples etiologías causan bastante incertidumbre diagnóstica en el equipo médico. En este artículo se presenta el caso de una paciente de 10 meses con una masa en el ala nasal de crecimiento rápido; se realiza un rápido diagnóstico de rabdomiosarcoma que requiere un adecuado manejo. El rabdomiosarcoma con patrón alveolar se presenta de forma inusual en esta ubicación, es por esto por lo que se considera importante presentar este caso para mantenerlo en el algoritmo diagnóstico como una posibilidad y que, así como en el caso presentado, se pueda tener un diagnóstico temprano, un tratamiento adecuado y un resultado estético y funcional favorable.

Given preferential nasal breathing in the first months of life in the pediatric population, nasal obstruction has more clinical repercussions than it would have in adults, hence the need to give higher priority to its diagnosis and management. One of the main causes of nasal obstruction in children is the presence of nasal masses, which cause considerable diagnostic uncertainty in the medical team, because of their multiple etiologies. In this article, the case of a 10-month-old patient with a rapidly growing mass in the nasal ala is presented. A rhabdomyosarcoma was promptly diagnosed and adequately managed. Rhabdomyosarcoma with an alveolar pattern occurs in an unusual way in this location; for this reason, this case is important in order to include this possibility in the diagnostic algorithm and, as was the case in this patient, reach an early diagnosis and institute adequate treatment resulting in favorable aesthetic and functional results.

Malignant alveolar neoplasm in a 10-month-old French bulldog

Background: Malignant tumors are the main cause of death or euthanasia in animals. The oral cavity ranking fourth in number of occurrences. Epidemiological studies with dogs suggest that canine cancer kills 40-50% of individuals aged over 10 years. In view of the interest of academics and professionals in the healthcare of dogs and cats, this paper reports the case of a 10-month-old bitch, which, despite being a young animal, was affected alveolar rhabdomyosarcoma of abrupt evolution. Case: A 10-month-old French Bulldog bitch, weighing 10 kg, was referred to a veterinary hospital in the city of Rio de Janeiro for care. It had a history of mouth bleeding, after chewing a solid mineral material, edema in the region of the right maxilla, and protusion of the gland of the third eyelid. As the clinical examination also revealed a fracture of the maxillary canine, anti-inflammatory and antibiotics were prescribed, to be administered by the owner once a day for 7 days. During the next clinical examination, carried out one week later, an edema was found in the right region of the mouth, which proved difficult to examine. As the patient had already eaten, an appointment was made for the following day for an intervention in the operating room, where the animal could be anesthetized for better observation of the effected region. Blood was collected for hemogram, urea, creatinine, alkaline phosphatase, ALT, and GGT, and an 8 h food fasting and a 4 h water fasting were recommended. On that date, once the dog had been taken to the operating room, was administered the pre anesthesia, in addition to anesthetic induction and manutention. Upon examining the oral cavity, several loose molars were found on the right side, in addition to a tumoral aspect of the gum; thus, it was decided to collect a small sample of the tumoral mass for histopathology. The surgical specimen was placed in a formalin solution and sent to the laboratory for histopathological processing and diagnosis. One week later, the tumor mass was larger and the edema in the right region of the mouth was much larger than on the day of the procedure. Thus, a computerized tomography was requested to further investigate the alterations that had occurred in such a short time. Due to the results of the histopathology and the CT, an immunohistochemical test was suggested which determined the cell profile and morphology and confirmed the diagnosis of alveolar rhabdomyosarcoma according to clinical suspicion. The animal remained in the veterinary hospital for a further 48 h, during which the clinical condition worsened, with the animal suffering heavy bleeding. As the patient was no longer capable of oral intake of food or water, the decision was made with the consent of the owners to induce a painless death to alleviate the suffering of the animal. However, the owners did not authorize a necropsy. Discussion: Veterinary physicians should be conscious of the treatment of serious illnesses that will not result in a benefit for the patient. They should know when to stop the treatment to not cause further pain and suffering to the animals and their owners. Many of the interventions which aim to treat severe malignant neoplasia will not promote an improvement in quality of life or significantly extend the patient's survival, and do not justify the suffering they entail. A painless death remains the best alternative in such cases.

Primary alveolar rhabdomyosarcoma of bone. / Rabdomiosarcoma alveolar primario de hueso. Reporte de un caso y revisión de la literatura.

INTRODUCTION: Rhabdomyosarcoma (RMS) is a malignant solid tumor of mesenchymal origin. It is the most com mon soft-tissue sarcoma in childhood and adolescence. 65% of cases are diagnosed before the age of 6. Histological subtypes include embryonal, alveolar, pleomorphic, and fused-cell RMS. The embryo nal subtype is more frequent in children, while the alveolar one is more frequent in adolescents and adults. OBJECTIVE: To describe the clinical presentation of primary alveolar rhabdomyosarcoma in a schoolgirl. CLINICAL CASE: 7-year-old schoolgirl with one-month history of progressive pain in her left thigh. X-ray shows a lytic lesion in the left femur diaphysis. A study was performed with 2 biopsies, immunohistochemistry, and PAX-FOXO1 studies which were compatible with alveolar RMS. Con clusion: Primary alveolar rhabdomyosarcoma of the bone is rare, but it should be considered within the differential diagnosis of primary small-round-blue cell bone tumors. Despite presenting a poor prognosis cytogenetic, this type of tumor seems to have better biological behavior, which for a successful treatment makes necessary to have a high index of suspicion in order to install a multimodal therapy in the context of a national protocol.

Rabdomiosarcoma alveolar con metástasis cardíaca en un paciente pediátrico / Alveolar rhabdomyosarcoma with cardiac metastasis in a pediatric patient

El rabdomiosarcoma es el tumor maligno de partes blandas más frecuente en la edad pediátrica. Puede afectar cualquier localización anatómica. El subtipo histológico alveolar suele causar lesiones en las extremidades en niños de mayor edad. Los sitios metástasicos más frecuentes son el pulmón, la médula ósea, el hueso y los ganglios linfáticos. Describimos el caso de un paciente con rabdomiosarcoma alveolar (RA) con metástasis cardíaca, una presentación poco frecuente de la patología.

Rhabdomyosarcoma is the most common malignant soft tissue tumor in pediatric age. It can affect any anatomical location. Alveolar histological subtype usually presents lesions on the extremities in older children. The most common metastatic sites are the lung, bone marrow, bone and lymph node. We describe a case of alveolar rhabdomyosarcoma with cardiac metastasis in a pediatric patient, a rare presentation of the pathology.

[Alveolar rhabdomyosarcoma with cardiac metastasis in a pediatric patient]. / Rabdomiosarcoma alveolar con metástasis cardíaca en un paciente pediátrico.

Rhabdomyosarcoma is the most common malignant soft tissue tumor in pediatric age. It can affect any anatomical location. Alveolar histological subtype usually presents lesions on the extremities in older children. The most common metastatic sites are the lung, bone marrow, bone and lymph node. We describe a case of alveolar rhabdomyosarcoma with cardiac metastasis in a pediatric patient, a rare presentation of the pathology.

El rabdomiosarcoma es el tumor maligno de partes blandas más frecuente en la edad pediátrica. Puede afectar cualquier localización anatómica. El subtipo histológico alveolar suele causar lesiones en las extremidades en niños de mayor edad. Los sitios metástasicos más frecuentes son el pulmón, la médula ósea, el hueso y los ganglios linfáticos. Describimos el caso de un paciente con rabdomiosarcoma alveolar (RA) con metástasis cardíaca, una presentación poco frecuente de la patología.

Alveolar rhabdomyosarcoma metastatic to the brain.

Alveolar rhabdomyosarcoma (ARMS) has a predilection for the peripheral extremities, and brain metastases are rare, with only a few cases reported after the initial diagnosis. We present a 22-year-old male patient with a right orbital-ethmoidal ARMS who presented with a recurrence to the brain 1 year after the initial diagnosis. He was referred to our institution due to acute neurological deterioration. A brain MRI was performed, showing an enhancing bilateral parafalcine lesion centred about the bilateral cingulate gyri with extension into the corpus callosum. The patient was taken to the operating room for a stereotactic biopsy under general anaesthesia, which was compatible with metastatic ARMS. Our case is exceedingly rare, considering the initial diagnosis of an orbital/ethmoidal ARMS, its subsequent metastasis to the brain and its clinical sequelae after a biopsy. Prognosis after cerebral metastatic ARMS is dismal, with most patients expiring due to central nervous system metastatic disease.

A Novel Germline TP53 Mutation in a Patient With Li-Fraumeni Syndrome: Resolving a Variant of Uncertain Significance.

Increasing availability of genomic testing poses new challenges to clinicians, particularly where variant interpretation from commercial sources may be equivocal. The authors report a patient with recurrent rhabdomyosarcoma and subsequent bilateral breast cancer who was found to harbor a previously undescribed germline TP53 sequence alteration annotated by the commercial laboratory as a variant of uncertain significance. By investigating publicly available databases of aggregated normal germline and malignant somatic genomic sequences, the authors conclude that this missense variant, c.476C>T (p.A159V), is a novel, pathogenic Li-Fraumeni syndrome mutation and demonstrate the utility of these resources in clinical pediatric hematology and oncology practice.

Vinorelbine and continuous low-dose cyclophosphamide as maintenance chemotherapy in patients with high-risk rhabdomyosarcoma (RMS 2005): a multicentre, open-label, randomised, phase 3 trial.

BACKGROUND: For more than three decades, standard treatment for rhabdomyosarcoma in Europe has included 6 months of chemotherapy. The European paediatric Soft tissue sarcoma Study Group (EpSSG) aimed to investigate whether prolonging treatment with maintenance chemotherapy would improve survival in patients with high-risk rhabdomyosarcoma. METHODS: RMS 2005 was a multicentre, open-label, randomised, controlled, phase 3 trial done at 102 hospitals in 14 countries. We included patients aged 6 months to 21 years with rhabdomyosarcoma who were considered to be at high risk of relapse: those with non-metastatic incompletely resected embryonal rhabdomyosarcoma occurring at unfavourable sites with unfavourable age (≥10 years) or tumour size (>5 cm), or both; those with any non-metastatic rhabdomyosarcoma with nodal involvement; and those with non-metastatic alveolar rhabdomyosarcoma but without nodal involvement. Patients in remission after standard treatment (nine cycles of ifosfamide, vincristine, dactinomycin with or without doxorubicin, and surgery or radiotherapy, or both) were randomly assigned (1:1) to stop treatment or continue maintenance chemotherapy (six cycles of intravenous vinorelbine 25 mg/m2 on days 1, 8, and 15, and daily oral cyclophosphamide 25 mg/m2, on days 1-28). Randomisation was done by use of a web-based system and was stratified (block size of four) by enrolling country and risk subgroup. Neither investigators nor patients were masked to treatment allocation. The primary outcome was disease-free survival in the intention-to-treat population. Secondary outcomes were overall survival and toxicity. This trial is registered with EudraCT, number 2005-000217-35, and ClinicalTrials.gov, number NCT00339118, and follow-up is ongoing. FINDINGS: Between April 20, 2006, and Dec 21, 2016, 371 patients were enrolled and randomly assigned to the two groups: 186 to stop treatment and 185 to receive maintenance chemotherapy. Median follow-up was 60·3 months (IQR 32·4-89·4). In the intention-to-treat population, 5-year disease-free survival was 77·6% (95% CI 70·6-83·2) with maintenance chemotherapy versus 69·8% (62·2-76·2) without maintenance chemotherapy (hazard ratio [HR] 0·68 [95% CI 0·45-1·02]; p=0·061), and 5-year overall survival was 86·5% (95% CI 80·2-90·9) with maintenance chemotherapy versus 73·7% (65·8-80·1) without (HR 0·52 [95% CI 0·32-0·86]; p=0·0097). Toxicity was manageable in patients who received maintenance chemotherapy: 136 (75%) of 181 patients had grade 3-4 leucopenia, 148 (82%) had grade 3-4 neutropenia, 19 (10%) had anaemia, two (1%) had thrombocytopenia, and 56 (31%) had an infection. One (1%) patient had a grade 4 non-haematological toxicity (neurotoxicity). Two treatment-related serious adverse events occurred: one case of inappropriate antidiuretic hormone secretion and one of a severe steppage gait with limb pain, both of which resolved. INTERPRETATION: Adding maintenance chemotherapy seems to improve survival for patients with high-risk rhabdomyosarcoma. This approach will be the new standard of care for patients with high-risk rhabdomyosarcoma in future EpSSG trials. FUNDING: Fondazione Città della Speranza, Association Léon Berard Enfant Cancéreux, Clinical Research Hospital Program (French Ministry of Health), and Cancer Research UK.

A large pelvic soft tissue mass implied by subtle bone scan findings.

An 18-year-old man with alveolar rhabdomyosarcoma and osseous metastases underwent bone scintigraphy to monitor the effect of chemotherapy. The images showed significant improvement of bone lesions. However, the scan revealed a vertically shaped urinary bladder and diffused increased activity in the genital region. A diagnostic pelvic CT was subsequently performed, which showed a thickened bladder wall, an ill-defined pelvic mass, and extensive subcutaneous edema in the genital region.

Bone marrow metastases from alveolar rhabdomyosarcoma with impressive FDG PET/CT finding but less-revealing bone scintigraphy.

An 18F-FDG PET/CT scan was performed in a 26-year-old man with a known alveolar rhabdomyosarcoma for staging. The PET/CT scan showed abnormally increased FDG activity involving almost all bones in the imaged regions. In contrast, 99mTc-MDP whole-body bone scan demonstrated only very limited bone metastases.

Rabdomiosarcoma alveolar metastásico a mama en adolescente: a propósito de un caso / Metastasic alveolar rabdomiosarcoma in breast of adolescent patient: a case report

La afección metastásica de la mama de una neoplasia extra mamaria maligna es un hecho infrecuente y constituye aproximadamente el 1,7% de todos los procesos malignos de la mama. Por otra parte, los sarcomas de tejidos blandos constituyen tan solo el 0,7% de todos los tumores malignos del organismo, por lo que es un hecho infrecuente encontrar en la mama una metástasis procedente de un sarcoma de partes blandas extra mamario, Se hace la referencia de un caso visto en el Hospital Coromoto de Maracaibo, paciente de 14 años con rabdomiosarcoma metastásico en mama izquierda, sin evidencia de enfermedad generalizada a quien se le practica mastectomía radical modificada, radioterapia y quimioterapia dándole así el tratamiento adecuado para este tipo de tumor

The condition of metastatic breast extra mammary malignant neoplasm is rare event and is about of 1.7% of all malignancies of the breast. On the other hand the soft tissue sarcomas constitute only 0.7% of incidence in relation to the all malignant tumors in the body, making it a rare event found in the breast, found metastasis from an extra mammary soft tissue sarcoma, reference is made a case view and treated in the Coromoto Hospital in Maracaibo city, is a patient 14 years old with metastatic rhabdomyosarcoma in the left breast with no evidence of widespread disease, who underwent modified radical mastectomy, giving chemotherapy and radiation therapy after surgery how a appropriate form of treatment for these kind of tumors

Superação: uma partilha de vida / Overcoming: a sharing of life

O artigo relata depoimento de mãe com filho dignosticado com Rabdomios sarcoma Alveolar. Sua superação diante desse desafio

The article reports mother's testimony with son dignosticado with Alveolar Rhabdomyo sarcoma. On overcoming this challenge

PAX7-FKHR fusion gene inhibits myogenic differentiation via NF-kappaB upregulation.

OBJECTIVE: Alveolar rhabdomyosarcomas (ARMS) are characterised by a PAX3/7-FKHR translocation, which is presumed to promote a differentiation arrest in the myogenic lineage, in which setting secondary genetic events occur, resulting in sarcomagenesis. The aim of this study was to identify the mechanism by which PAX3/7-FKHR expression results in a myogenic differentiation block, as discrete from the secondary genetic events that complete the sarcomagenic process. METHODS: We performed a novel differential gene expression analysis comparing normal mesenchymal stem cells with previously generated non-tumorigenic mesenchymal stem cells expressing the PAX7-FKHR fusion gene, as well as with a known tumorigenic, PAX7-FKHR-expressing ARMS cell line, CW9019. RESULTS: This novel analysis uncovered the upregulation of the NF-kappaB pathway as a function of PAX3/7-FKHR expression, but distinct from the secondary sarcomagenic process; thus implicating NF-kappaB as a mediator of the PAX3/7-FKHR differentiation block. We further show that NF-kappaB activity is upregulated in PAX7-FKHR cells when compared to parental MSCs due to upregulation of the PI3K/AKT pathway. In addition we show that NF-kappaB inhibits myogenesis via activation of cyclinD1/ cdk4 complexes, which sequester MyoD1, a key myogenic transcription factor. CONCLUSIONS: Our results highlight the importance of the NF-kappaB pathway in myogenesis and sarcomagenesis and suggest that this pathway may be one of the potential therapeutic targets in the treatment of ARMS.

Primary cutaneous alveolar rhabdomyosarcoma in a pediatric patient.

Rhabdomyosarcoma is the most common soft tissue tumor in childhood; however, it rarely affects only the skin. This case report describes a child with a painful nodule on her face. Histopathology and immunohistochemistry confirmed the diagnosis of rhabdomyosarcoma, and a multidisciplinary team then followed up the patient. Soft tissue tumors are responsible for 6% of all childhood tumors, and 53% of these are rhabdomyosarcomas, which may affect any part of the body. Presentation in the form of skin nodules is rare and represents a diagnostic challenge, since there are no clinical characteristics that differentiate this condition from other pathologies.

Rabdomiossarcoma alveolar cutâneo primário em paciente pediátrico / Primary cutaneous alveolar rhabdomyosarcoma in a pediatric patient

O rabdomiossarcoma é o tumor de partes moles mais comum na infância, sendo raro o acometimento exclusivamente cutâneo. Apresenta-se caso de criança com nódulo doloroso na face, cuja análise histopatológica e imunoistoquímica confirmou tratar-se de rabdomiossarcoma, o qual foi conduzido por equipe multidisciplinar. Os tumores de partes moles são responsáveis por 6 por cento de todos os tumores infantis; destes, 53 por cento são rabdomiossarcomas, que podem acometer qualquer sítio. A manifestação como nódulo dérmico é incomum, representando um desafio diagnóstico, já que não possui características clínicas que o diferenciem de outras patologias.

Rhabdomyosarcoma is the most common soft tissue tumor in childhood; however, it rarely affects only the skin. This case report describes a child with a painful nodule on her face. Histopathology and immunohistochemistry confirmed the diagnosis of rhabdomyosarcoma, and a multidisciplinary team then followed up the patient. Soft tissue tumors are responsible for 6 percent of all childhood tumors, and 53 percent of these are rhabdomyosarcomas, which may affect any part of the body. Presentation in the form of skin nodules is rare and represents a diagnostic challenge, since there are no clinical characteristics that differentiate this condition from other pathologies.