PRIMARY BONE LIPOSARCOMA IN CHILDREN
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1 CASE PRESENTATIONS 12 PRIMARY BONE LIPOSARCOMA IN CHILDREN Ingrid Miron 1,2, Gabriel Aprodu 1,2, Doina Mihaila 2, Petru Plamadeala 2, Oana Tatiana Miron 1, Anamaria Ciubara 1,3, Lucian Miron 1,4, Marin Burlea 1,2, Stefana Maria Moisa 1,2, Laurentiu Lucaci 1,5 1 Gr. T. Popa University of Medicine and Pharmacy, Iasi 2 Sf. Maria Emergency Clinical Hospital, Iasi 3 Socola Psychiatry Hospital, Iasi 4 Regional Oncology Institute, Iasi 5 Prof. Dr. George Georgescu Institute of Cardiovascular Diseases, Iasi ABSTRACT Introduction. Even though the soft tissue liposarcoma is a frequent tumor, the primary bone liposarcoma is very rare, being localized especially in the long bones. Material and meyhod. We present the case of a 14 years old female child, hospitalized in the Sf. Maria Emergency Clinic Hospital for Children Iasi accusing pain, functional impairment and tumefaction in the right arm, symptoms which suddenly occurred about 24 hours prior to presentation, following a falling trauma on the right arm. The bone x-ray emphasized a tumor in the proximal part of the humerus bone, associated with a pathological fracture. Results. A biopsy form the tumor was performed and the pathology report (histology and immunohistochemistry) documented a malignant liposarcomatous proliferation. Conclusion. The fi nal pathology diagnosis, correlated with the clinical fi ndings, which excluded the possibility of a bone metastasis, was that of a primary bone liposarcoma. Case particularity: very rare tumor, witch presented with a pathological bone fracture. In establishing the diagnosis of a bone liposarcoma it is very important to exclude a bone metastasis from a liposarcoma with a primary localization other than the bone, as well as other primary bone tumors. The prognosis seems to be better than in the osteosarcoma but liposarcoma presents a higher rate of local recurrence and systemic dissemination. Keywords: bone, liposarcoma, child INTRODUCTION Primary bone liposarcoma are extremely uncommon tumors, despite the fact that the bone marrow is rich in adipose cells. The disease is sufficiently rare to justify reporting isolated cases. CASE PRESENTATION Female child, 14 years-old, is admitted in the Pediatric Surgery Department for pain, functional impairment, tumefaction localized in the right arm, symptoms with a sudden onset 24 hours prior to presentation. She had no pathological history and a good performance status at the time of the presentation. The local exam: 1/3 proximal region of the right hummers bone tumefaction, of firm consistency, painful both spontaneously and when mobilized, limiting the passive and active movements in the scapulohumeral joint. The laboratory tests revealed an inflammatory syndrome: neutrophilia, elevated fibrinogen and lymphopenia. The radiological exam of the right arm reveals an osteolytic lesion in the 1/3 proximal region of the humerus and a right humerus pathological fracture. The CT scan is suggestive for an osteosarcoma and a pathological fracture, without displacement. Surgery is performed and multiple biopsies from the bone tumor and the peritumoral areas are done, Corresponding author: Stefana Maria Moisa, Sf. Maria Clinical Emergency Hospital, 62 Vasile Lupu Street, Iasi stephaniemed@yahoo.com REVISTA ROMÂNÅ DE PEDIATRIE VOLUMUL LXIII, NR. 3, AN
2 286 REVISTA ROMÂNÅ DE PEDIATRIE VOLUMUL LXIII, NR. 3, AN 2014 one drain tube was installed and postoperative immobilization in swaddle for two weeks was performed. The extemporaneous exam of the tumor performed during the surgical intervention on frozen sections coloured with Blue toluidine is suggestive for a liposarcoma, which is why a special frozen coloration is performed Scharlach. The suspicion is thus strengthened by the presence of the fatty drops from the tumor cells cytoplasm. Prints: May-Grumwald-Giemsa staining infrequent tumor cells with atypical cyto-nuclear features and optical empty vacuoles in some of the cells. Infrequent inflammatory cells present. Paraffin: fragment from the extemporaneous exam and number 3 surgical piece represents an adipocyte-like tumoral cellular proliferation with a marked cyto-nuclear pleomorphism and sarcomatous vessels in the stroma. Infrequent bone lamellas with an isolated aspect and the following characteristics: 1. connective tissue is infiltrated with tumor proliferation bone lamellas 2. tumor proliferation with myxoid areas and round cells areas. 3. tumor infiltrate in the bone tissue 4. tumor proliferation, myxoid cells areas, round cells areas, tumor necrosis. Immunohistochemistry: CD34 positive in the vessel s walls and the presence of capillary with a branch aspect S100 positive in some tumor cells like adult lipocyte and negative in all other tumor cells Ki67 positive in different proportion 50% in myxoid areas and 80% in round and pleomorphic cells areas. Final diagnosis: Bone liposarcoma with round cells, high malignancy grade, G3, T2a STAGING. TREATMENT. EVOLUTION The thoraco-abdominal CT scan revealed multiple secondary hepatic and vertebral lesions (D9, D10, D11, L1, L3), suggesting secondary pulmonary lesions. In this context we classified the liposarcoma as stage IV and initiated a chemotherapy protocol recommended in soft tissue sarcoma in advanced stages: Ifosfamide + Doxorubicin (Ifosfamide 1500 mg/m 2 with Mesna (urological protection) days and Doxorubicin 20 mg/m 2 /day, days 1-2-3). The protocol is to be repeated every 3 weeks, according to Worden et al (1). Unfortunately, response to treatment was unsatisfactory and the disease extensively recurred locally three months from the diagnosis. DISCUSSIONS The bone liposarcoma is exteremely rare tumor in pediatric population with an incidence of less than 0,1% of all primary bone tumors (2). All age groups may be affected, but the usual onset is seen in adulthood (3), while the children are rarely afflicted (only 5 cases being currently reported) (2,4, 5,6,7). The most frequent localization is in the long bones: tibia, femur, humerus (3, 8), while wide bones (scapula, skull) and vertebrae are seldom affected (9). The clinical features are dominated by a painful tumor mass and the radiology exam de- FIGURE 1. 1 Humeral CT scan, lateral; 2 Humeral CT reconstruction, median view; 3 Humeral CT reconstruction, lateral view; 4 Print. MGG, x400; 5 Extemporaneous exam. Scharlach, x 100; 6 Extemporaneous exam. AT, x200
3 REVISTA ROMÂNÅ DE PEDIATRIE VOLUMUL LXIII, NR. 3, AN FIGURE 2. 1 S100 x100; 2 CD34 x100; 3 Ki67 x100; 4 CK AE1/ AE3 x100; 5 CD68 x100; 6 CD45 x200 scribes a limited, expansive, osteolytical bone tumor. CT/MRI describes the lypidic component of the tumor. The histological variants are similar to those of the soft tissue liposarcoma (3): lipoma-like well differentiated liposarcoma, myxoid/round cells liposarcoma, pleomorphic liposarcoma. The differential diagnosis includes the soft tissue liposarcoma with local bone extension/metastasis (3), primary bone tumor, lypoma and other malignant tumors like osteosarcoma and Ewing sarcoma. Surgical excision remains the main form of therapy (broad excision/amputation and prosthesis). The role of chemotherapy is controversial but may be helpful for high- grade tumours (protocols for soft tissue liposarcoma (2)) and also local radiotherapy. The prognosis is related to the histological type: pleomorphic liposarcoma has the least favorable prognosis (3) with an overall survival of less than three years from the diagnosis (10). Well-differentiated and myxoid types have a 100% and 88% 5-year disease free survival rates respectively (4). The prognosis of the bone liposarcoma is generally unfavorable, but it is better than that of osteosarcoma (2). Tumors with poorly circumscribed margin or those with local recurrences after surgery have a poor prognosis, although they rarely metastasize (5). Repeated local recurring liposarcomas may evolve into a high grade sarcoma with metastatic potential. There is a high probability of local recurrence and metastasis, most commonly to the lung (9), (10). CONCLUSION Bone liposarcoma is a very rare bone tumor in children; the presentation in our case was that of a pathological bone fracture. The advanced stage (IV) at the moment of the diagnosis and the lack of response to the chemotherapy led to the unfavorable evolution. REFERENCES 1. Worden F.P., Taylor J., Biermann J., Sondak V., Leu K., Chugh R., McGinn C., Zalupski M., Barker L. Randomized Phase II Evaluation of 6 g/m 2 of Ifosfamide Plus Doxorubicin and Granulocyte Colony- Stimulating Factor (G-CSF) Compared With 12 g/m 2 of Ifosfamide Plus Doxorubicin and G-CSF in the Treatment of Poor-Prognosis Soft Tissue Sarcoma, J.Clin.Oncol (23) 2005: Macmull S., Dushan H., Atkinson E., Saso S., Tirabosco R., O Donnell P., Skinner J. Primary intra-osseous liposarcoma of the femur: a case report, Journal of Orthopaedic Surgery 2009; 17(3): World Health Organization Classifi cation of Tumors: Pathology and Genetics of Tumors of Soft Tissue and Bone, IARC Press, Lyon, 2012, Cai C.Q., Zhang Q.J., Ma X., Sun N., Wang C.X. Primary Liposarcoma of Temporal Bone in a Child, HK J Paediatr. 2006; 11: Rabah R., Ryan J., Farmer D., Ravindranath Y. Primary Liposarcoma of Bone in an Adolescent: A Case Report, Int J Surg Pathol 1999; 7: Rasalkar D.D., Chow L.T., Chu W.C., Cheng F.W., Li C.K. Primary pleomorphic liposarcoma of bone in an adolescent: imaging features of a rare entity, Pediatr Radiol 2011; 41(10): Ross C., Hadfield G. Primary osteo-liposarcoma of bone (malignant mesenchymoma), The Journal of Bone and Joint Surgery 1968; 50B(3): World Health Organization Classification of Tumors: Pathology and Genetics of Tumours of Soft Tissue and Bone, IARC Press, Lyon, 2002, Barra de Moraes F., Cardoso A., Newton A., Wilson E., Daher S., de Souza Carneiro S., Parrode N., Barbosa M., de Lima Malta N., Ribeiro N. Primary liposarcoma of the lombar spine: case report, Rev Bras Ortop. 2012;47(1): Hamlat A., Saikali S., Gueye E., Le Strat A., Carsin-Nicol B., Brassier G. Primary liposarcoma of the thoracic spine: case report, Eur Spine J 2005; 14:
4 PREZENTĂRI DE CAZ 12 LIPOSARCOM OSOS PRIMAR LA COPIL Ingrid Miron 1,2, Gabriel Aprodu 1,2, Doina Mihăilă 2, Petru Plamădeală 2, Oana Tatiana Miron 1, Anamaria Ciubară 1,3, Lucian Miron 1,4, Marin Burlea 1,2, Ştefana Maria Moisă 1,2, Laurenţiu Lucaci 1,5 1 Universitatea de Medicină şi Farmacie Gr. T. Popa, Iaşi 2 Spitalul Clinic de Urgenţă pentru Copii Sfânta Maria, Iaşi 3 Spitalul Clinic de Psihiatrie Socola, Iaşi 4 Institutul Regional de Oncologie, Iaşi 5 Institutul de Boli Cardiovasculare Prof. Dr. George Georgescu, Iaşi REZUMAT Introducere. Deşi liposarcomul de ţesuturi moi este o tumoră frecventă, liposarcomul primar osos este foarte rar, fiind localizat în special în oasele lungi. Material şi metodă. Prezentăm cazul unei paciente în vârstă de 14 ani, spitalizată în Spitalul Clinic de Urgenţă pentru Copii Sfânta Maria din Iaşi pentru durere, impotenţă funcţională şi tumefacţia bratului drept, simptome ce au debutat cu 24 de ore anterior internării, ca urmare a unui traumatism prin cădere al braţului drept. Radiografia osoasă a evidenţiat o masă tumorală în porţiunea proximală a humerusului, asociată cu o fractură patologică. Rezultate. S-a realizat o biopsie la nivelul tumorii, iar analiza anatomopatologică (histologică şi imunochimică) a documentat proliferare liposarcomatoasă malignă. Concluzie. Diagnosticul anatomopatologic fi nal, corelat cu examenul fi zic, care a exclus posibilitatea unei metastaze osoase liposarcomatoase, a fost aceea de liposarcom primar osos. Particularitatea cazului: tumoră foarte rară, cu prezentare iniţială de fractură osoasă patologică. În stabilirea diagnosticului de liposarcom osos primar, trebuie exclusă posibilitatea unei metastaze de la un liposarcom cu localizare iniţială extraosoasă, ca şi pe cea a unui alt tip de tumoră osoasă primară. Prognosticul pare a fi mai favorabil decât cel al osteosarcomului, dar liposarcomul prezintă o rată mai mare de recurenţe locale şi diseminări sistemice. Cuvinte cheie: os, liposarcom, copil INTRODUCERE Liposarcoamele osoase primare sunt tumori extreme de rare, în ciuda faptului că măduva este bogată în celule adipoase. Boala este suficient de rară pentru a justifică raportarea unor cazuri izolate. PREZENTAREA CAZULUI Pacienta în vârstă de 14 ani este internată în Clinica de Chirurgie Pediatrică pentru durere, impotenţă funcţională, tumefacţie a braţului drept, simptome cu debut brutal cu 24 de ore anterior internării. Pacienta nu prezenta antecedente patologice semnificative şi avea mobilitate păstrată la momentul prezentării. Examen local: tumefacţie la nivelul treimii proximale a humerusului, având consistenţă fermă, durere prezentă spontan şi la palpare, limitând miş cările pasive şi active ale articulaţiei scapulohumerale. Testele de laborator au evidenţiat prezenţa sindromului inflamator: neutrofilie cu limfopenie şi fibrinogen crescut. Examenul radiologic al braţului evidenţiază o leziune osteolitică în treimea proximală a humerusului şi o fractură patologică la acest nivel. Examenul computer tomografic este sugestiv pen tru osteosarcom şi fractură patologică, fără deplasare. S-a realizat intervenţia chirurgicală de excizie tumorală şi s-au prelevat multiple biopsii din tu- Adresa de corespondenţă: Dr. Ştefana Maria Moisa, Spitalul Clinic de Urgenţă pentru Copii Sfânta Maria, Str. Vasile Lupu, nr. 62, Iaşi stephaniemed@yahoo.com REVISTA ROMÂNÅ DE PEDIATRIE VOLUMUL LXIII, NR. 3, AN
5 346 REVISTA ROMÂNÅ DE PEDIATRIE VOLUMUL LXIII, NR. 3, AN 2014 moră şi ţesutul peritumoral; s-a instalat un tub de dren şi s-a realizat imobilizare postoperatorie cu du rata de două săptămâni. Examenul extemporaneu al tumorii realizat în timpul intervenţiei chirurgicale pe secţiuni îngheţate colorate cu albastru de toluidine este sugestiv pentru liposarcom, motiv pentru care se realizează coloraţia specială Scharlach. Suspiciunea este astfel întărită de prezenţa inclusiunilor grăsoase în citoplasma celulelor tumorale. Amprente: Coloraţie May-Grumwald-Giemsacellule tumorale rare cu trăsături citonucleare atipice şi vacuole optic clare în unele celule. Celule in fl amatorii rare. Parafina: fragment din specimenul extemporaneu şi piesa 3 de excizie chirurgicală, reprezentând o proliferare celulară tumorală similară adipocitelor cu marcat pleiomorfism citonuclear şi vase sarcoma toase în stroma. Lamele osoase rare cu aspect izolat şi următoarele caracteristici: 1. Ţesut conectiv infiltrat cu lamele osoase din proliferarea tumorală. 2. Proliferare tumorală cu zone mixoide şi zone de celule rotunde. 3. Infiltrat tumoral în ţesutul osos. 4. Proliferare tumorală, arii de celule mixoide, arii de celule rotunde, necroză tumorală. Imunohistochimie: CD34 pozitiv în pereţii vasculari şi prezenţa de capilare cu aspect terminal. S100 pozitiv în unele celule tumorale cum ar fi lipocitele adulte şi negative în alte celule tumorale. Ki67 pozitiv în proportii diferite 50% în ariile mixoide şi 80% în zonele cu celule rotunde şi pleiomorfe. Diagnostic final: Liposarcom osos cu celule rotunde, grad înalt de malignitate, G3, T2a STADIALIZARE. TRATAMENT. EVOLUŢIE Computer tomografia toraco-abdominală a relevant multiple leziuni secundare hepatice şi vertebrale (D9, D10, D11, L1, L3), sugerând şi leziuni pulmonare secundare. În acest context, am clasificat liposarcomul ca fiind în stadiul IV şi am iniţiat un protocol chimioterapic recomandat în sarcoamele de ţesuturi moi în stadia avansate: Ifosfamida + Doxorubicina (Ifosfamida mg/m 2 cu Mesna (pentru protective urologică în zilele şi Doxorubicina 20 mg/ m 2 /zi, în zilele 1-2-3). Acest protocol a fost repetat la fiecare 3 săptămâni, conform Worden et al (1). Din nefericire, răspunsul la tratament a fost nesatisfăcător şi pacienta a prezentat o recurenţă locală extensivă la trei luni de la momentul diag nosticului. DISCUŢII Liposarcomul osos este o tumoră extrem de rară în populaţia pediatrică, cu o incidenţă de mai puţin de 0,1% din totalul tumorilor osoase primare (2). Toate grupele de vârstă pot fi afectate, dar debutul tipic este situat în timpul perioade de adult (3), în timp ce copiii sunt rar afectaţi (doar 5 cazuri fiind raportate până în prezent) (2,4-7). Cea mai frecventă localizare este la nivelul oaselor lungi: tibia, femurul, humerusul (3,8), în timp ce oasele late (scapula, craniul) şi vertebrele sunt rareori afectate (9). Trăsăturile clinice sunt dominate de o masă tu- FIGURA Examen CT humeral, lateral; 2. Reconstrucţie CT humerală, vedere mediană; 3. Reconstrucţie CT humerală, vedere laterală; 4. Amprentă. MGG, x 400; 5. Examen extemporaneu. Scharlach, x 100; Examen extemporaneu. AT, x 200
6 REVISTA ROMÂNÅ DE PEDIATRIE VOLUMUL LXIII, NR. 3, AN FIGURA S100 x1 00; 2. CD34 x100; 3. Ki67 x100; 4. CK AE1/ AE3 x100; 5. CD68 x100; 6. CD45 x200 morală dureroasă, iar examenul radiologic descrie o tumoră osoasă limitată, expansivă. Examenul CT sau MRI descrie componenţa lipidică a tumorii. Variantele histologice sunt similare liposarcomului de ţesuturi moi (3): liposarcom bine diferenţiat si milar lipomului, liposarcom cu celule mixoide sau rotunde, liposarcom pleiomorfic. Diagnosticul di fe - renţial include liposarcomul de ţesuturi moi cu extensie sau metastază locală osoasă (3), tumora primară osoasă, lipomul şi alte tumori maligne ca osteosarcomul şi sarcomul Ewing. Excizia chirurgicală rămâne principala formă de tratament (excizie largă sau amputare şi protezare). Rolul chimio terapiei este controversat, dar aceasta poate fi de ajutor în tumorile cu grad mare de malignitate (pro tocoalele pentru liposarcomul de ţesuturi moi (2)), la fel cu radioterapia. Prognosticul este legat de tipul histologic: liposarcomul pleiomorfic are prognosticul cel mai puţin favorabil (3), cu speranţa de supravieţuire mai mică de trei ani de la momentul diagnosticului (10). Tipurile bine diferenţiate şi cele mixoide au rate de supravieţuire la 5 ani fără recăderi de 100% şi 88%, respectiv (4). Prognosticul liposarcomului osos este în general nefavorabil, dar este mai bun decât cel al osteo sarcomului (2). Tumorile cu margini imprecis delimitate sau cele cu recurente locale după intervenţia chirurgicală au prognostic rezervat, deşi metastazează foarte rar (5). Liposarcoamele cu recurenţe locale repetate pot evolua la sarcom de grad înalt cu potenţial metastatic. Există o probabilitate crescută de recurenţă locală şi metastazare, cel mai frecvent la nivel pulmonar (9,10). CONCLUZII Liposarcomul osos este o tumoră foarte rară la copil; motivele primului consult medical în cazul prezentat au fost reprezentate de o fractură patologică. Stadiul avansat (IV) la momentul diagnosticului şi lipsa de răspuns la chimioterapie au dus la o evoluţie nefavorabilă.
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