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Uncommon sarcomas of the uterine cervix: a review of selected entities.

Sarcomas constitute less than 1% of all cervical malignancies. With over 150 reported cases, rhabdomyosarcomas represent the most commonly reported sarcoma at this location. In this report, a select group of the more uncommon sarcomas of the uterine cervix are reviewed, including all previously reported examples of leiomyosarcoma, liposarcoma, alveolar soft part sarcoma, Ewing sarcoma/primitive neuroectodermal tumor, undifferentiated endocervical sarcoma, and malignant peripheral nerve sheath tumor (MPNST). Emphasis is placed on any distinctive clinicopathologic features of these entities at this unusual location.

Journal Article↗

Digital image processing of crystalline specimens examined by electron microscopy.

Crystalline specimens imaged in the electron microscope are analysed using digital processing. Some principles of structural analysis using the method of Fourier decomposition are discussed. Complementary techniques, such as enhancement by gradient and Laplacian operators, have been found useful in analysing electron micrographs. The application of these techniques to some problems in Materials Science and Biology are reviewed. By selecting and phase-correcting spots in the computed diffraction pattern, it was possible to localize atoms, molecules, and their defective arrangement in evaporated gold, sputter-deposited tungsten films, and single crystals of cadmium selenide. Digital processing based on the theory of helical diffraction was used to explore the three-dimensional arrangement of molecules in cellular components of alveolar soft part sarcoma, Hirano bodies, and neurofibrillar tangles in the human brain.

Actins↗

An unusual association between oral sarcoma and bulbar palsy.

A 90 year old male presented with symptoms and signs of right lower cranial nerves palsy. A small mass was found on the right side at the back of his mouth. Light microscopy and histoimmunochemical studies of the biopsy of the mass showed an alveolar soft part sarcoma arising from the right myohyoid muscle. The unusual location and presentation of this rare tumor is discussed.

Aged↗

Low-affinity nerve growth factor receptor (p75) in dermatofibrosarcoma protuberans and other nonneural tumors: a study of 1,150 tumors and fetal and adult normal tissues.

Low-affinity nerve growth factor receptor (p75) is a member of the tumor necrosis factor receptor family. It may modulate the binding of nerve growth factor (NGF) to the functional high-affinity receptor tyrosine kinase (trk) A. NGF is thought to be responsible for growth, apoptosis, and function of the nervous system. The presence of this receptor (p75) was determined in a large group of neural and nonneural tumors and fetal and adult tissues. One thousand one hundred fifty tumors were analyzed with monoclonal antibody for p75, along with selected normal fetal and adult tissues. Immunoreactivity for p75 was present in adult pericytes, perivascular fibroblasts, basal cells of several types of epithelia, perineurial cells, and dendritic reticulum cells. Additionally, a wide zone of subepithelial mesenchyme and skeletal muscle were positive in the first-trimester fetus, but were diminished or negative in the adult. Consistently positive nonneural mesenchymal tumors included dermatofibrosarcoma protuberans (DFSP), embryonal and alveolar rhabdomyosarcoma, synovial sarcoma, and spindle cell hemangio(endotheli)oma. Schwann cell tumors, ganglioneuroma, granular cell tumor, and malignant peripheral nerve sheath tumor (MPNST) were also p75 positive. Mesenchymal nonneural tumors that were variably positive (32% to 69%) for p75 included fibrosarcoma variants, solitary fibrous tumor, hemangiopericytoma, spindle cell lipoma, Ewing's sarcoma, mesenchymal chondrosarcoma, and malignant melanoma. Nervous system tumors such as paragangliomas, neuroblastoma, meningioma, and perineurioma and nonneural mesenchymal tumors, including extraskeletal osteosarcoma, benign fibrous histiocytomas, fibromas, alveolar soft part sarcoma, epithelioid sarcoma, smooth muscle and gastrointestinal stromal tumors, and angiosarcomas, were almost always negative for p75. Epithelial tumors that were consistently positive included mixed tumor and adenoid cystic carcinoma, whereas mesothelioma, adenocarcinomas, and most squamous cell carcinomas were negative. p75 is not a specific marker for nerve sheath tumors. It is present in a variety of other mesenchymal tumors including synovial sarcoma and in CD34-positive tumors such as DFSP, spindle cell lipoma, and hemangiopericytoma. The presence of p75 in nonneural tumors such as DFSP and rhabdomyosarcoma mimic its presence in early fetal mesenchyme and skeletal muscle, suggesting oncofetal expression in these tumors. p75 may be useful to distinguish DFSP from benign fibrous histiocytoma.

Connective Tissue↗

Epithelial-type and neural-type cadherin expression in malignant noncarcinomatous neoplasms with epithelioid features that involve the soft tissues.

CONTEXT: Transmembrane adhesion molecules, epithelial-type cadherin (ECAD) and neural-type cadherin (NCAD), help in regulating transformations between epithelial and mesenchymal cells in the developing embryo and in maintaining the epithelioid phenotype. Consequently, the presence of epithelioid cells in certain malignant noncarcinomatous neoplasms raises speculation that the expression of ECAD and NCAD in these neoplasms may have diagnostic significance. OBJECTIVE: To investigate the utility of ECAD and NCAD immunoexpression in distinguishing malignant (noncarcinomatous) neoplasms with epithelioid features that involve the soft tissues. DESIGN: Membranous immunoreactivity of anti-ECAD and anti-NCAD was evaluated on archived cases selected from the files of the Armed Forces Institute of Pathology. RESULTS: Epithelial-type cadherin was found in biphasic synovial sarcoma (35 of 35 cases), malignant melanoma (13/21), monophasic fibrous synovial sarcoma (13/26), clear cell sarcoma (4/9), poorly differentiated synovial sarcoma (3/13), diffuse mesothelioma (4/20), malignant epithelioid peripheral nerve sheath tumor (1/6), and epithelioid sarcoma (5/62). Neural-type cadherin was observed in chordoma (11/11), biphasic synovial sarcoma (30/35), diffuse mesothelioma (14/20), malignant melanoma (14/25), epithelioid sarcoma (24/63), epithelioid angiosarcoma (1/4), poorly differentiated synovial sarcoma (2/13), clear cell sarcoma (1/10), and monophasic fibrous synovial sarcoma (1/26). Eighteen cases of primary cutaneous squamous cell carcinomas all tested positive for ECAD, whereas NCAD was focally observed in 5 cases. No expression of either molecule was observed in cases of epithelioid hemangioendothelioma (n = 9), alveolar soft part sarcoma (n = 8), and extraskeletal myxoid chondrosarcoma (n = 7). CONCLUSIONS: Epithelial-type and neural-type cadherins are found in a variety of noncarcinomatous neoplasms with epithelioid features that involve the soft tissues and can be utilized, in association with other immunomarkers, in distinguishing chordoma (100% NCAD) from extraskeletal myxoid chondrosarcoma and conventional chondrosarcoma of bone (0% NCAD), squamous cell carcinoma (100% ECAD) from epithelioid sarcoma (8% ECAD), and biphasic synovial sarcoma (100% ECAD) from diffuse mesothelioma (20% ECAD).

Biomarkers, Tumor↗

Expression of E-cadherin in bone and soft tissue sarcomas: a possible role in epithelial differentiation.

The cadherin-mediated cell-cell adhesion system is now known to play a critical role in both the morphogenesis of cancer cells and suppression of their invasion. However, the pattern of expression of E-cadherin, the major cadherin of epithelial cells in bone and soft tissue sarcomas, remains unclear. This prompted us to study E-cadherin expression in a variety of bone and soft tissue sarcomas. Using the monoclonal antibody HECD-1, raised against the extracellular domain of E-cadherin, we observed immunoreactivity in 1 pleomorphic rhabdomyosarcoma, 2 of 5 diffuse mesotheliomas, 4 of 5 clear cell sarcomas, 1 of 5 epithelioid sarcomas, and 10 synovial sarcomas. Other types of bone and soft tissue sarcoma (4 osteosarcomas, 4 chondrosarcomas, 3 primitive neuroectodermal tumors, 1 fibrosarcoma, 4 malignant fibrous histiocytomas, 5 liposarcomas, 4 leiomyosarcomas, 6 alveolar and 5 embryonal rhabdomyosarcomas, 4 angiosarcomas, 4 malignant peripheral nerve sheath tumors, 2 extraskeletal myxoid chondrosarcomas, 2 extraskeletal osteosarcomas, and 3 alveolar soft part sarcomas) were completely negative for E-cadherin. Our findings indicate that E-cadherin is expressed in certain kinds of soft tissue sarcomas, especially those with epithelioid features, suggesting that E-cadherin plays a role in the constitution of their architecture.

Bone Neoplasms↗

Recent advances in pediatric renal neoplasia.

Over the past 6 years, molecular genetic studies have significantly advanced our understanding of pediatric renal neoplasms. The cellular variant of congenital mesoblastic nephroma (but not the classic variant) has been shown to bear the same t(12;15)(p13;q25) and ETV6-NTRK3 gene fusion as infantile fibrosarcoma, a tumor with which it shares morphologic and clinical features. Rhabdoid tumor of the kidney is characterized by deletion of the hSNF5/INI1 gene, which links it to other rhabdoid tumors of infancy that arise in the soft tissue and brain. Primary renal synovial sarcomas and renal primitive neuroectodermal tumors have become accepted entities, and likely comprise a subset of what had previously been termed "adult Wilms tumor." Renal carcinomas associated with Xp11.2 translocations that result in fusions involving the TFE3 transcription factor gene have been delineated, including a distinctive neoplasm that shares the identical gene fusion as alveolar soft part sarcoma. Most recently, a distinctive type of renal neoplasm with a t(6;11)(p21;q12) has been described, and the cloning of the resulting gene fusion links it to the Xp11 translocation carcinomas. Together, these last two translocation-associated tumors represent a significant proportion of pediatric renal cell carcinomas. This review highlights each of these recent advances.

Adolescent↗

[Christopherson's tumor. Review of the literature apropos of a retroperitoneal localization].

Alveolar soft-part sarcoma is rare, and its retroperitoneal localization in psoas major muscle, exceptional. Concerning a case occurred in a young woman, the authors focus on the characters of this tumor of unknown histogenesis which affects predominantly young adults, mainly females. This disease, which symptomatology is poor and which evolution is particularly long for such a neoplasm, leads inexorably to death despite surgical treatment that represents to date, the unique efficient therapeutic modality.

Adult↗

Rhabdomyosarcoma in middle-aged and elderly individuals.

In a review of a national series of malignant tumors in middle-aged and elderly individuals (over 40 years of age), in all 107 cases primarily diagnosed and reported to the Swedish Cancer Registry as rhabdomyosarcomas during the period 1972-1981, 4 cases were accepted as botryoid, embryonal or alveolar rhabdomyosarcoma, using light-microscopic criteria for the diagnosis. An electron-microscopic and immunohistochemical analysis was performed on the 4 cases along with 7 cases of botryoid, embryonal and alveolar rhabdomyosarcoma in patients of over 40 years of age obtained from our own files. Rhabdomyoblastic differentiation was established ultrastructurally by the presence of myofilaments and Z-like densities in 10 of these 11 cases. There were tumor cells in the formaldehyde-fixed, paraffin-embedded material which were positively stained for desmin in all cases, for myoglobin in 7/11 cases, for vimentin in 5/11 cases and for actin in all cases, using monoclonal antibodies. The demonstration of desmin by the monoclonal antibody which was used on the formaldehyde-fixed, paraffin-embedded material is of particular value in the diagnosis of rhabdomyosarcoma. Another tumor, located in the minor pelvis, lacked the light-microscopic features of botryoid, embryonal or alveolar rhabdomyosarcoma, but presented ultrastructural and immunohistochemical evidence of a rhabdomyoblastic differentiation. This tumor was epithelioid in appearance and shared features with alveolar soft part sarcoma. The label epithelioid rhabdomyosarcoma is proposed for this tumor. Nine pleomorphic sarcomas were selected from the national series as possible pleomorphic rhabdomyosarcomas because of the presence of ribbon-shaped tumor cells with an eosiniphilic cytoplasm. There was no electron-microscopic or immunohistochemical evidence of a myogenic differentiation in any of these 9 tumors. The present investigation indicates that a pleomorphic type of rhabdomyosarcoma, indistinguishable from embryonal, botryoid and alveolar rhabdomyosarcoma, is extremely rare or non-existent.

Adult↗

Angiomyolipoma and PEComa are immunoreactive for MyoD1 in cell cytoplasmic staining pattern.

The family of tumors derived from mesenchymal perivascular epithelioid cells (so-called PEComas) includes angiomyolipoma, lymphangioleiomyomatosis, clear cell sugar tumor of the lung, clear cell myomelanocytic tumor of ligamentum teres/falciform ligament, and abdominopelvic sarcoma of perivascular epithelioid cells. These tumors were characterized by coexpression of melanocytic (HMB-45) and muscle markers. MyoD1 transcription factor has crucial role in commitment and differentiation of mesenchymal progenitor cells to myogenic lineage. Antibodies to MyoD1 protein (nuclear immunoreactivity) have been shown highly valuable adjuncts in the diagnosis of rhabdomyosarcomas. To evaluate expression of the transcription factor MyoD1 in PEComas, we performed immunohistochemistry. Monoclonal antibody 5.8A for MyoD1 was used on a series of cases of formalin-fixed, paraffin-embedded angiomyolipoma (n = 19), lymphangioleiomyomatosis (n = 3), clear cell sugar tumor of the lung (n = 1), and abdominopelvic sarcoma of perivascular epithelioid cells (n = 2). All cases showed strong granular immunostaining in the tumor cell cytoplasm with the anti-MyoD1 antibody. Cytoplasmic reactivity was noted in the spindle cells, fat cells, and epithelioid cells. Nuclei were negative in all tumors studied, and a clean background was obtained. Several normal and neoplastic human tissues have also been immunostained for MyoD1 without any positive cytoplasmic staining, with the exception of 2 alveolar soft part sarcomas. Cytoplasmic immunostaining with monoclonal antibody 5.8A for MyoD1 in PEComas may correspond to cross-reactivity with an undetermined cytoplasmic protein. Great caution should be exercised in interpreting the immunostaining results with anti-MyoD1 antibody 5.8A.

Angiomyolipoma↗

Phase II trial of pegylated-liposomal doxorubicin (Doxil) in sarcoma.

Pegylated-liposomal doxorubicin (Doxil) is a unique form of liposomal doxorubicin in which the liposomes are coated with methoxypoly (ethylene glycol), resulting in a diminished uptake by the reticuloendothelial system, leading to a longer half-life in blood and a different toxicity profile than nonpegylated liposomes. We performed a phase II study of Doxil in sarcoma. The patient population was primarily previously treated or had diagnoses considered unresponsive to chemotherapy. The initial dose per course was 55 mg/m2 every four weeks with dose modification based on mucositis and hand-foot syndrome (the main limiting toxicities). Treatment was generally well tolerated. Of 214 evaluable treatment courses in 47 patients, toxicities were mild and similar to previous reports, but dose reduction was common. No definite cardiac toxicity was observed. There were: 6 osteosarcomas, 3 Ewings, 1 extraosseous osteosarcoma, 1 chondrosarcoma, 2 alveolar soft part sarcomas, 15 gastrointestinal stromal cell tumors (GIST), and 19 other soft tissue sarcomas. Three of the 47 patients received a CR or PR, although 15 of the 47 patients were felt to have derived clinical benefit from the treatment. Some responses were delayed. These data suggest that pegylated-liposomal doxorubicin has activity in this population of poor prognosis sarcoma and that this treatment is associated with modest toxicity.

Adult↗

Aggressive pulmonary metastasectomy for soft tissue sarcomas.

BACKGROUND: To evaluate the efficacy of aggressive pulmonary metastasectomy for treating soft tissue sarcomas, the clinical data on the surgical management of 23 patients with extensive pulmonary metastases from soft tissue sarcomas were reviewed. METHODS: Between January 1973 and April 1991, 9 male patients and 14 female patients were treated. Their ages ranged from 13-68 years (median, 42 years). Twenty-one patients (91%) had bilateral and multiple metastases, and two patients had solitary metastasis. The number of resected metastatic nodules ranged from 1-110 (mean, 30.5). As an initial surgical approach, median sternotomy was used on 18 patients and lateral thoracotomy on 5 patients. Eleven patients underwent two or more explorations for recurrent metastases using lateral thoracotomy. The neodymium:yttrium-aluminum-garnet (Nd:YAG) laser was adopted in 10 patients since 1986. RESULTS: The actuarial 2-year and 5-year survival rates after the first pulmonary resection were 49.7% and 24.8%, respectively. Histologic type (alveolar soft part sarcoma versus synovial sarcoma, P < 0.025), histologic grade (G1 and G2 versus G3, P < 0.01), and metastatic localization (subpleural versus extrapleural, P < 0.005) were the most significant prognostic factors for aggressive pulmonary metastasectomy of soft tissue sarcomas. Application of laser surgery, absence of local recurrences, and absence of extrapulmonary metastases before pulmonary resection also correlated with better prognosis with borderline significance. CONCLUSIONS: Aggressive pulmonary metastasectomy for soft tissue sarcomas is a recommended procedure, even in the case of extensive metastases. The combination of median sternotomy and Nd:YAG laser-assisted surgery is a useful technique, especially in bilateral multiple pulmonary metastases.

Adolescent↗

Are myogenin and myoD1 expression specific for rhabdomyosarcoma? A study of 150 cases, with emphasis on spindle cell mimics.

Rhabdomyosarcoma (RMS), the most common soft tissue sarcoma of childhood, displays a variety of histologic patterns. Immunohistochemistry is used extensively to distinguish RMS from its mimics. Myogenin and MyoD1, myogenic transcriptional regulatory proteins expressed early in skeletal muscle differentiation, are considered sensitive and specific markers for RMS and are more specific than desmin and muscle-specific actin and more sensitive than myoglobin. Previous studies have focused on expression of myogenin and MyoD1 in small round cell tumors. This study assesses myogenin and MyoD1 in rhabdomyosarcoma subtypes and spindle cell tumors considered in the differential diagnosis of RMS. Formalin-fixed, paraffin-embedded archival tissue from 32 RMS, 107 non-RMS, and 11 benign skeletal muscle samples was stained for myogenin and MyoD1 with standard immunohistochemical techniques. Nuclear positivity was scored on a three-tiered scale. All RMSs expressed myogenin. Alveolar RMS (ARMS) showed strong nuclear staining, especially in tumor cells lining fibrous septae and perivascular regions. In cases with a subtle alveolar architecture on routinely stained sections, myogenin highlighted and enhanced visualization of the alveolar morphologic pattern. Embryonal RMSs (ERMSs) were more variable in myogenin staining pattern and intensity. No cases of nodular fasciitis, malignant fibrous histiocytoma, malignant peripheral nerve sheath tumor, inflammatory myofibroblastic tumor, myofibrosarcoma, leiomyoma, leiomyosarcoma, or alveolar soft part sarcoma stained for myogenin. Focal nuclear reactivity was seen in desmoid (2 of 10), infantile myofibromatosis (2 of 10), synovial sarcoma (1 of 10), and infantile fibrosarcoma (2 of 10). Non-neoplastic skeletal muscle fiber nuclei stained positively for myogenin in both tumor-associated samples (25 of 40) and benign skeletal muscle samples (5 of 11). Although all RMSs were immunoreactive for MyoD1, cytoplasmic and nonspecific background staining and reactivity of nonmyoid tissues hindered its practical utility in paraffin-embedded samples in this study. Although myogenin is a highly sensitive and specific marker for RMS, it is rarely seen in other spindle cell soft tissue tumors. As previously reported, ARMS stained more strongly than ERMS. In contrast to previous studies, rare non-RMS (7 of 107) displayed focal nuclear reactivity, and entrapped atrophic or regenerative skeletal muscle fibers also stained positively. Although these are potential pitfalls in the interpretation of myogenin, careful attention to morphology and other features, to the relative paucity of myogenin-positive nuclei in non-RMS. and to the presence of entrapped muscle fibers should prevent incorrect interpretation. Because the extent of myogenin expression in RMS is much greater than in non-RMS, it is a very useful marker when interpreted in the context of other clinicopathologic data.

Biomarkers, Tumor↗

Metastatic nonrhabdomyosarcomatous soft-tissue sarcomas in children and adolescents: the St. Jude Children's Research Hospital experience.

BACKGROUND: Because the natural history of pediatric patients with metastatic nonrhabdomyosarcomatous soft-tissue sarcomas (NRSTS) had not been well described, we retrospectively reviewed our single-institution experience with these tumors. PROCEDURE: We identified 26 patients with metastatic NRSTS who were treated at St. Jude Children's Research Hospital from December 1971 through July 1995. We evaluated the characteristics of each patient, including age, sex, primary site, stage, type of therapy received, and outcome. Sites of metastatic disease at diagnosis and relapse were noted. RESULTS: The median age of the 26 study patients at diagnosis was 14. 8 years; 54% of patients were male and 69% were white. The most common histologies were synovial sarcoma, alveolar soft-part sarcoma, and malignant fibrous histiocytoma. Most primary tumors (73% of cases) occurred in the trunk or extremities. Most patients presented with large (>5 cm), high-grade lesions. All 26 patients received chemotherapy, and 8 responded to an ifosfamide- or cyclophosphamide-doxorubicin-based regimen. Radiotherapy was administered to 15 patients, and 13 had a partial or complete resection of the primary tumor. Six patients underwent thoracotomy. The estimated 2-year survival for the cohort was 34.6% +/- 8.9%; the 2-year progression-free survival was 15.4% +/- 6.3%. The lung was the most common site of failure. CONCLUSIONS: Children with metastatic NRSTS have a poor outcome, which is similar to that in adults. More effective systemic chemotherapy is needed to facilitate complete surgical resection of primary and metastatic sites. Aggressive pulmonary metastatectomy can increase disease control.

Adolescent↗

Melanoma of the soft parts: diagnosis of metastatic and recurrent tumors by aspiration cytology.

Three cases of melanoma of the soft parts diagnosed by aspiration cytology and immunochemistry are described. Unusual clinicoradiological features, variable cytomorphology, absence of melanin, and lack of awareness due to rarity of the lesion caused diagnostic dilemma. Morphological similarity to alveolar soft part sarcoma, synovial and epithelioid sarcoma, cutaneous melanoma, poorly differentiated carcinoma, and plasmacytoma were noted. Consideration of clinical data such as age, site, and radiology was helpful in narrowing down the diagnosis. A presumptive cytologic diagnosis helped in selecting the antibody panel, which established the definitive diagnosis in all cases. This approach is valuable in preoperative management and obviates the need for an open biopsy in primary, metastatic, or recurrent tumor. Increasing experience in fine-needle aspiration of this rare entity and correlation with immunochemistry and histopathology are valuable in narrowing down the differential diagnosis, reducing diagnostic errors, and widening its clinicocytological spectrum.

Adult↗

Adult type (nonembryonal) soft tissue sarcomas in childhood.

Nonembryonal soft tissue sarcomas are rare in childhood. We report our experience from a series of 28 patients treated at this centre, whose treatment was based on primary surgical resection. No patient required limb amputation. Anatomical distribution and histological subtypes differed from the adult sarcoma population. A total of 79 percent of the sarcomas were classified as high grade. Six patients (21%) developed local recurrence, and 6 patients (21%) developed distant recurrence, including 3 patients (11%) who developed both. Median follow-up was 57 months. Actuarial 5 years survival was 82%, which compares favorably with the 5 year survival of adults with high grade soft tissue sarcomas treated at this centre (63%) and with the survival of children with embryonal sarcomas treated by chemotherapy.

Adolescent↗

Adolescent breast masses in Nigerian Igbos.

In the Igbos of Nigeria, most adolescent breast masses were due to gynecomastia in males and to fibroadenoma in females. The peak ages for both diseases differed from those reported in a recent American series. An exotic finding was a mammary mass due to onchocerca worms. Curiously, there were as many as two cases of a rare tumor, namely, alveolar soft part sarcoma.

Adenocarcinoma↗

Pulmonary metastasectomy in pediatric patients.

This article describes the historical development of pediatric pulmonary metastasectomy but demonstrates that progress has been slow in understanding its proper applications. Because many pediatric metastatic tumors are rare, surgeons have grouped together patients of different histologies for the generation and analysis of case series. By examining tumor types individually, however, it is seen that certain histologies (adrenocortical carcinoma, alveolar soft part sarcoma, osteosarcoma) mandate surgical metastasectomy for patient survival. Other pediatric tumors (Wilms tumor, Ewing's sarcoma) are radiation sensitive, and the application of metastasectomy is controversial. In the case of still other types of tumor (neuroblastoma, differentiated thyroid cancer, rhabdomyosarcoma), metastasectomy is seldom performed except in highly unusual situations. Techniques for minimally invasive biopsy and for muscle-sparing thoracotomy are described for pediatric patients.

Biopsy↗