CHAPTER 17 Paediatric tumors
Clinical aspects
Incidence of paediatric tumors and histologic types
Paediatric tumors show a distinctive incidence, histology, and biologic behavior from those in adults. In addition, fetal and neonatal malignancies tend to differentiate or regress spontaneously, leading to high survival and curability rates.1 In the United States, only 2% of patients with a malignancy are in the paediatric age group, with almost 9000 children under the age of 15 presenting with a malignancy each year.2 Even with improved overall 5-year survival from 27% in 1960 to over 70% in the 1990s, cancer still remains a leading cause of childhood mortality. The type of malignancy varies considerably within age groups. In children younger than 5 years, acute lymphoblastic leukemia is the most frequent and most lethal cancer.3 The most common solid tumours of childhood are primary posterior fossa brain tumors and teratoma, followed by neuroblastoma and soft tissue sarcomas. Osteosarcoma is the most common primary bone tumor followed by Ewing’s sarcoma.
Diagnostic accuracy of FNA cytology
Fine needle aspiration biopsy (FNAB) has many advantages in the diagnosis of paediatric tumors, especially the ease of performance and repeatability with no essentially morbidity or risk of tumor upstaging.4–6 Centers experienced in performing paediatric FNAB have shown excellent results with sensitivity and specificity rates approaching 93% and 100%, respectively, comparable to those in the adult population.5–21 The availability and applicability of diagnostic ancillary techniques such as histochemistry, immunocytochemistry, electron microscopy, flow cytometry, cytogenetics, and molecular analysis to the cytology smears often enable the pathologist to give a definitive diagnosis.
FNAB of paediatric mass lesions has been slow in gaining popularity compared with its utilization in adult patients.5–21 Many pathologists and clinicians are hesitant to employ fine needle aspiration (FNA) as a diagnostic method in children for a variety of reasons, including rarity of paediatric tumors with different morphology from those of adults, lack of experience of general pathologist with such tumors, morphological overlap between different tumor types, lack of specific immunocytochemical markers and unrepresentative samples as a result of degenerative changes or tumors with heterologous components such as hepatoblastoma or Wilms’ tumor. These lead to difficulties in interpretation of FNA of paediatric tumors.1,22 There is a recent decline in the number of aspirates from patients with a history of cancer as a result of recent advances of image techniques to document recurrence and relapses.23
Obtaining and handling of specimens
Some centers, such as ours, have been using FNA as the first diagnostic modality in the work-up of mass lesions (superficial and deep seated) in children for providing rapid diagnostic results, thereby aiding in proper triage and management of the patient.20,24–26 Intraoperative cytology (IOC) can be useful in cases with limited tissue available, leading to a rapid assessment of the nature of the lesion, thereby, optimizing triage of tissue for the most appropriate ancillary studies (cultures, cell blocks, cytogenetics, flow cytometry, etc.). This allows for preservation of tissue for permanent section examination, especially in HIV-positive patients (avoiding cryostat contamination), or tissue prone to difficulties in cutting at the time of frozen section such as bony fragments and fatty specimens.
We use both the Papanicolaou and Romanowsky stains since the two are complimentary. Nuclear features such as chromatin distribution and granularity are better evaluated on the Papanicolaou stain, while the Romanowsky stain is superior for evaluation of lymphoreticular lesions (benign and malignant). Lesions with stromal and matrix components are also more easily discernible by Romanowsky staining, such as the bright magenta color of neuropil in the case of neuroblastoma. For immunocytochemistry, a cell block preparation works best. However, direct smears and cytospins can also be used.26
Ancillary techniques
Nowhere has the use of immunohistochemistry and molecular genetic studies impacted the rendering of histogenetic-specific diagnoses more than in the childhood soft tissue sarcomas, particularly small round cell tumor (SRCTs).21,27 As most paediatric patients are enrolled in histogenetic-specific protocols (e.g. Paediatric Oncology Group) following a diagnosis of sarcoma, most authors agree that although the gold standard for diagnosis remains the light microscopic evaluation, ancillary diagnostic procedures are helpful to render the specific subtyping of SRCTs.27 FNAB permits a rapid diagnosis with the availability of performing ancillary techniques such as immunocytochemistry, flow cytometry, cytogenetics, and electron microscopy (EM). It is for these reasons that FNA has been incorporated by many institutions into the diagnostic algorithm of paediatric tumors. Cell block preparations are the ideal for performance of immunocytochemical studies as they allow the performance of a panel of IHC markers. Gurley et al. reviewed the diagnostic contribution of ancillary studies performed on aspirated material in the work-up of paediatric biopsies.28 Ancillary studies were performed in 40% of their cases. Immunohistochemistry helped to narrow the differential diagnosis or classify the disease process in 42%, confirm the cytologic impression in 47%, and gave contradictory results in 10% of cases. Seventy-four percent of cases had adequate material for electron microscopy which was diagnostic or helped to classify the lesions in one-third of cases, helped exclude diagnostic consideration in 21% and was noncontributory in only 14% of cases.28
The utility of FNA material in the molecular characterization has been shown in several studies, and the majority of aspirates can yield sufficient material to perform the necessary molecular studies.22,28–30 In a study by Kilpatrick et al., among 27 patients clinically eligible for histogenetic-specific protocols, an accurate diagnosis was rendered by FNA in 25 (92%) cases.21 Kilpatrick and colleagues also showed that cytogenetic analysis can be accurately performed using FNA biopsy material to confirm the t(11;22) translocation in Ewing’s sarcoma and the t(x;18) translocation in synovial sarcomas, supporting the FNA cytologic impression (Table 17.1).21
Diagnostic approach
An approach to the cytologic work-up of paediatric FNA is to divide lesions conceptually into two broad groups based on the size of the malignant cells, uniformity of cell appearance, and patterns of cell arrangement.24 The majority of paediatric malignancies can be classified into either the small or large cell categories, although there are occasional tumors such as rhabdomyosarcoma that have cytologic features that bridge both groups.20 This is especially important since many of the paediatric malignancies fall into the category of small round cell (blue cell) tumors (SRCTs) of childhood.2,20,31 These neoplasms consist of a uniform cell populations having diameters up to approximately three times that of a small mature lymphocyte and typically possess only a single hyperchromatic nucleus with finely granular, evenly distributed chromatin. The cytoplasm is generally scanty, resulting in very high nuclear to cytoplasmic ratios. The much less frequent ‘large cell’ category of malignancies is composed of pleomorphic cell populations with more abundant cytoplasm and may include multinucleated cells.20 Characteristically, coarsely clumped chromatin with irregular distribution and prominent nucleoli are present. However, for both categories, particularly SRCTs, definitive diagnosis often requires ancillary studies such as immunocytochemistry, EM, cytogenetic and molecular studies.21,23,25,28,32
Cytological findings
Small round cell tumors (SRCTs)
Definitive cell typing of SRCT is mandatory for enrollment of patients in specific therapeutic protocols, which has led to a significant increase in the disease-free survival rates. Immediate cytologic assessment is a critical step that helps to establish the initial diagnostic impression and points to the need for additional tissue material for pertinent ancillary studies.25,29,33 Aktar et al.26 and Layfield15 have expressed the importance of a complete history, physical examination, and radiological and laboratory evaluations in arriving at a definitive diagnosis of SRCTs.
Neoplasms which are conventionally considered in the SRCT category include the prototypical neuroblastoma along with rhabdomyosarcoma, Ewing’s sarcoma/primitive neuroectodermal tumor (EWS/PNET), intra-abdominal desmoplastic small round cell tumor, leukemia and malignant lymphoma.10,34 Other childhood malignancies that are in the differential diagnosis include small cell osteosarcoma, undifferentiated (small cell) hepatoblastoma, blastemal Wilms’ tumor, rhabdoid tumor of soft tissue, synovial sarcoma and granulocytic sarcoma.35,36
All SRCTs are uniformly characterized by the presence of sheets of monomorphic cells with subtle architectural and cytomorphologic features that serve as clues to the correct diagnosis.22 Morphological similarity and lack of immunocytochemical specificity in SRCT are reasons for difficulties in specific diagnosis of SRCT on cytology.22 Some SRCTs are so poorly differentiated that they lack specific antigens. In addition, cross-reactivity exists for many antigens among certain SRCTs.22 However, correct cell typing is possible and achievable in 92% of FNAB of SRCTs with the judicious use of various ancillary studies.4,18,21 A variety of cytologic variables including nuclear, cytoplasmic, and architectural features were analyzed as to their association with the final histologic typing to determine the most predictive characteristics for each sarcoma. Using the previous cytologic features, Layfield et al. performed logistic regression analysis of 59 cases with diagnoses of Ewing’s sarcoma/PNET, rhabdomyosarcoma, neuroblastoma, Wilms’ tumor and lymphoma.34 Among the entire group, Ewing’s sarcoma/PNET was the most difficult to specifically diagnose by cytomorphology alone. In most cases, it was the ‘lack’ of diagnostic criteria for the other round cell sarcomas that was used to make a diagnosis of Ewing’s sarcoma.34
Neuroblastoma is considered the ‘prototypical’ small round cell tumor of childhood.25 It is the most common solid nonlymphoreticular malignancy in the paediatric age group, with the majority of patients diagnosed before 5 years of age and 50% before 2 years of age. It is also the most common malignancy in the neonate.20,37,38
Neuroblastoma can be found in any site which harbors sympathetic neural tissue. The most common sites of occurrence, comprising two-thirds of cases, are the adrenal gland and retroperitoneal sympathetic ganglia.18 Neuroblastoma also occurs in other neural crest sites such as the thoracopulmonary, mediastinal, cervical and, less commonly, pelvic regions.2,20,30 Approximately one-third of children with neuroblastoma present with metastatic disease to regional lymph nodes, bone marrow, liver, bone and/or lung at the time of diagnosis.37,38 The prognosis of patients with neuroblastoma correlates with age, site of involvement and stage. Adrenal neuroblastoma has a less favorable prognosis than its extra-adrenal counterpart.14 In addition, the presence of a stroma-rich matrix, low mitotic–karyorrhectic cell index, and increased numbers of differentiating tumor cells are correlated with favorable prognosis.35,39–41
Neuroblastoma usually forms a well-defined solid tumor <10 cm in size with hemorrhage and extentive necrosis. The FNA usually yields hypercellular smears with predominant individually scattered small anaplastic cells, showing prominent nuclear molding.27,41,42 The prototypical neuroblastic cells have high nuclear to cytoplasmic ratios with single nuclei that are oval to slightly irregular in shape containing evenly dispersed granular chromatin (salt and pepper) and small to inconspicuous nucleoli (Fig. 17.1). Small round cells are arranged in moderately or well-formed Homer-Wright rosettes surrounding centrally located neuropil, which stains pink or blue–gray in Giemsa-stained smears. The presence of Homer-Wright rosettes is diagnostic but not present in all cases (Fig. 17.2). Neuropil, either associated with the rosettes or present in the smear background, is the most helpful cytologic feature for rendering a definitive cytologic diagnosis of neuroblastoma.34 Neuropil consists of a fibrillary tangle of neuritic processes with or without associated neuroblastic cells (Fig. 17.3). Mitotic–karyorrhectic cells and calcifications can occasionally be recognized in aspirate smears. Larger differentiating neuroblasts with moderate amounts of cytoplasm and binucleated to multinucleated ganglion cells can also be present in the smear. Some neuroblastomas may undergo different grades of maturation, forming ganglioneuroblastoma or ganglioneuroma. In ganglioneuroblastoma, the smear is pleomorphic with prominent anisonucleosis and abundant neuropil background but without ganglion cells, while ganglioneuroma demonstrates characteristic ganglion cells (Fig. 17.4).27,42
The differential diagnosis of neuroblastoma includes other members of SRCTs group.42 The presence of apoptotic nuclei, nuclear molding, paranuclear ‘blue bodies’, necrotic background, with the absence of lymphoglandular bodies will help to distinguish neuroblastoma from lymphomas.24,43 Neuroblastoma composed of dissociated primitive cells without rosettes formation, is morphologically undistinguishable from blastema cells of a Wilms’ tumor or EWS/PNET. The immunocytochemical profile supportive of neuroblastoma includes positive staining for neuron-specific enolase (NSE), microtubule-associated proteins (MAPs) and/or neurofilament protein.28 Positive staining for S-100 and/or glial fibrillary acidic protein (GFAP) has occasionally been observed. CD56 can be positive in both neuroblastoma cells and EWS/PNET. However, CD56 was reported uniformly and strongly positive in all neuroblastomas and only focally in EWS/PNET.28,43 In addition, EWS/PNET is usually positive for CD99, while neuroblastoma CD99 is usually negative. Conversely, Wilms tumor can be WT1 negative in 30% and CD56 positive.43 In this setting, low molecular weight cytokeratin is helpful to differentiate neuroblastoma from Wilms’ tumor, since Wilms’ tumor is cytokeratin positive while neuroblastoma is negative, although blastema cells can occasionally be cytokeratin negative.22 Neuroblastomas are negative for desmin, myogenin, smooth muscle actin, muscle-specific actin, CD34, and CD45.43 Ultrastructural features of neuroblastoma include small dense core neurosecretory-type granules and abundant processes containing microtubules.43 Neuroblastoma usually shows a deletion or rearrangement of material of chromosome 1p and amplification of N-myc.44
This is the most frequent intraocular tumor in children, with similar cytomorphology to neuroblastoma. One-third of these tumors are bilateral and are usually seen in children younger than 2 years. Retinoblastomas appear as high-grade undifferentiated small round cell tumors. Smears show hypercellular smears formed by sheets of small round or oval hyperchromatic nuclei with numerous mitoses and inconspicuous nucleoli, often with necrotic background.1,5 Cells show molding and typically arranged in rosettes with a central lumen containing acid mucopolysaccharides resistant to hyaluronidase (Flexner-Wintersteiner rosettes), and less frequently in Homer-Wright rosettes, in which cells are arranged around neuropil matrix.4
Nephroblastoma is the most frequent malignancy of the kidney in childhood and accounts for 6% of all paediatric cancers.20,29 Wilms tumor (WT) is the most frequent paediatric cancer in children less than 3 years old. Approximately 90% of all intra-abdominal malignancies in childhood will be either Wilms’ tumor or neuroblastoma.20 The preoperative diagnosis of Wilms’ tumor by FNA biopsy has become increasingly important since neoadjuvant chemotherapy has become the standard of care.45,46
Wilms’ tumors usually present as a single tumor, but it is sometimes multicentric and bilateral. Most cases are >10 cm in size and has a soft consistency, even surface, and well-delimited border with frequent areas of necrosis and hemorrhage.1 FNA biopsy for the primary diagnosis and management of Wilms’ tumor is contraindicated in children with a resectable renal mass.47 However, patients with unresectable Wilms’ tumor requiring neoadjuvant chemotherapy, or children with metastatic disease at the time of presentation may benefit from FNAB technique.48,49 According to the current guidelines,48 FNA through a posterior approach does not upstage the tumors, while an anterior approach technique, will upstage the tumor to stage III because of the possibility of generalized peritoneal contamination.
FNAB of conventional Wilms’ tumor shows a triphasic pattern consisting of complex tubules (epithelial component), mesenchymal differentiation and a primitive blastemal component.20,35 The blastemal cells are characterized by a relatively small size with high nuclear to cytoplasmic ratios and only a scant rim of extremely fragile cytoplasm (Figs 17.5 and 17.6). Nuclear molding can also be seen. The larger cells of the epithelial component may be arranged in tubules which range from simple tubular outlines to complex, branching luminal patterns (Fig. 17.7). These tubules have a well-defined apical border surrounding an empty luminal space with palisading of the epithelial nuclei. They can potentially be confused with the Homer-Wright rosettes of neuroblastoma.42–51 However, Homer-Wright rosettes are less complex in architecture and consist of cells arranged around central fibrillary neuropil. The mesenchymal component of Wilms’ tumor consists of fibroconnective tissue fragments containing short spindle-shaped cells with bland nuclear features, which can occasionally predominate and demonstrate a myxoid or collagenous appearance in the smears. Occasional cases can show skeletal muscle differentiation. Histologically, anaplasia in Wilms’ tumor is defined as the combination of enlarged nuclei equal to or greater than three times the size of the nuclei of adjacent cells along with nuclear hyperchromasia and abnormal multipolar mitotic figures.45 Recognition of anaplasia is crucial since it is associated with aggressive tumor behavior and decreased survival, thereby necessitating more aggressive therapy. An overdiagnosis of anaplasia in the aspirated smears, however, can be due to a number of artifacts such as calcification and stain precipitate which can simulate enlarged hyperchromatic nuclei. DNA-smearing artifact and basophilic extracellular mucinous material can also simulate anaplastic nuclei. Conversely, sampling errors can lead to an underdiagnosis of anaplasia.45
![image](https://i0.wp.com/basicmedicalkey.com/wp-content/uploads/2017/06/B9780702031519000177_f017-006-9780702031519.jpg?w=960)
Fig. 17.6 Wilms’ tumor (nephroblastoma)
Blastemal cells can surround and/or be incorporated into stromal fragments (Diff-Quik, ×200).
Separation of WT from other SRCTs can be extremely difficult, particularly if the undifferentiated blastemal component is the predominant or sole component in the smears.45,51 A careful search for epithelial and mesenchymal components favors WT, whereas a fibrillary background confirms the diagnosis of intrarenal neuroblastoma.50 Ancillary studies become crucial in rendering a specific diagnosis and separating this lesion from other SRCTs. In WT, blastemal cells stain positively for vimentin, cytokeratin (AE1/AE3), epithelial membrane antigen (EMA) and CD99 negative.30,50,52 Neuroblastomas are positive for neuron-specific enolase (NSE) but negative for cytokeratin and EMA. Lymphomas can occur in the kidney and are characterized by leukocyte common antigen (LCA, CD45) positive. The background typically demonstrates abundant diagnostic lymphoglandular bodies.
Ewing’s sarcoma/primitive neuroectodermal tumor (EWS/PNET)
Ewing’s sarcoma/primitive neuroectodermal tumor is the second most frequent malignant paediatric primary bone tumor, accounts for approximately 20% of soft tissue sarcomas in the first 2 decades of life and is the most common thoracic neoplasm.20,21,53 Around 25% of patients have metastasis in the lungs and bones at the time of diagnosis. Both PNET and Ewing’s sarcoma stain positively with monoclonal antibodies FLI-1 and CD99 (MIC-2 oncogene) and share a common chromosomal abnormality (11;22 translocation).27 The demographic and biologic behavior of both lesions are similar enough to consider these lesions as a continuous spectrum of the same tumor.54,55
Smears are cellular, composed of small cohesive groups of undifferentiated small round cells without nuclear molding (Fig 17.8). Although single dispersed cells are seen in the smear background, EWS/PNET can yield the most cohesive pattern of the SRCTs group. The cells have indistinct borders and may form pseudorosettes. A dimorphic population of lighter and darker cells may be present in Diff-Quik-stained smears, mimicking the histologic findings. Lighter-staining cells are large (approximately the size of histiocytes) and have round-to-oval, slightly pleomorphic nuclei, smooth nuclear membranes with fine chromatin and one or two small nucleoli. Cells have a moderate amount of finely vacuolated-to-clear cytoplasm that contains abundant, periodic acid–Schiff-positive, diastase-digestible glycogen granules.56 Darker-staining or lymphocytoid cells have a small, irregularly contoured nucleus with dense chromatin and a narrow rim of cytoplasm, changes that are likely a manifestation of apoptosis. The two cell types are usually intermingled in no discernible pattern, with lighter-staining cells predominating. Binucleation, multinucleation, and stromal matrix formation are not features of EWS/PNET. Homer-Wright rosettes are not usually seen. In the Diff-Quik smear, peripheral cytoplasmic vacuolization and membranous cytoplasmic blebs can be noted in occasional cases and considered as characteristic features.56,57
In rare cases of EWS/PNET, the majority of the cell population has slightly oval nuclei, mimicking other SRCTs, particularly monophasic synovial sarcoma. The so-called large cell variant of EWS/PNET may be confused with large cell lymphoma, but immunophenotyping settles this diagnostic issue in most cases.55,56
Although positive staining for CD99 is quite helpful in the diagnosis of PNET/Ewing’s sarcoma, it is not specific.22,30 CD99 can be demonstrated in various percentages in other SRCTs. CD99 was reported in 57–100% of lymphoblastic lymphomas, 34–44% of neuroblastomas, 11–30% of rhabdomyosarcoma, 35–81% of DSRCT and 62% of synovial sarcomas.22,30 Ewing/PNET tumors can be negative for CD99 (8.6%). EWS/PNET can be occasionally positive for cytokeratin and desmin (about 10%). Molecular analysis plays an important diagnostic role in doubtful cases, whereas 90% show t(11;22)(q24;q12) translocation, while 10% show t(21;22)(q22;q12) translocation.22,30,54,55
Rhabdomyosarcoma (RMS) is the most frequent soft tissue sarcoma in children with two age peaks, with the first peak occurring at 4 to 5 years of age and the second in late adolescence.21 It arises often in the head and neck, followed by genitourinary tract, extremities, and trunk of children younger than 5 years old. In the paediatric population, there are two major histologic forms: the alveolar and embryonal subtypes. Embryonal subtype is the most common form in early age. In contrast, the alveolar subtype is more frequently seen in adolescents and originates most often in the extremities, paranasal sinuses and retroperitoneum.58
Although rhabdomyosarcoma is generally considered one of the SRCTs of childhood, it is associated with a relatively broad spectrum of histologic appearances.58,59 FNA demonstrates a wide range of morphology and the degree of variability greater than that seen in the other SRCTs.4 Aspiration biopsies of both embryonal and alveolar rhabdomyosarcomas are characterized by moderately to highly cellular samples which include both numerous individually dispersed tumor cells (rhabdomyoblasts) and densely packed aggregates with prominent overlapping of the cells.45,60 The smear background may show characteristic loose myxoid material which may have a metachromatic appearance with the Romanowsky stains. In other instances, the smear background is simply clean, collagenous or bubbly (tigroid) in appearance, resembling that seen in aspirates from germinomas.4,45,54,59 Some investigators have attempted to differentiate embryonal from alveolar subtype in FNAC smears and were successful in 80% of cases. The embryonal subtype may be composed almost exclusively of small primitive cellular elements with round or polygonal contours, extremely high N : C ratios, solitary nuclei and minute nucleoli. Some cells may show a higher level of differentiation with increasing volumes of eosinophilic cytoplasm and eccentrically positioned nuclei, mimicking rhabdoid tumors (Fig. 17.9).4,59 Smears of alveolar rhabdomyosarcoma are more cellular with more mature rhabdomyoblasts than embryonal rhabdomyosarcoma.59,60 Rhabdomyoblastic cells may be arranged in alveolar structures. Compared with the embryonal subtype, the malignant cells comprising the alveolar subtype of rhabdomyosarcoma are generally larger and more uniform in appearance with rounded contours, solitary hyperchromatic nuclei, prominent nucleoli and high N : C ratios (Fig. 17.10). A helpful diagnostic feature of alveolar subtype is the presence of multinucleated tumor giant cells with nuclei arranged in a wreathlike manner (Fig. 17.10). Characteristic strap cells with a solitary tapered cytoplasmic tail may be occasionally seen.58,61,62 Pohar-Marinsek and Bracko observed that the alveolar rhabdomyosarcoma exhibited two major architectural patterns: one characterized by completely dissociated cells and the other one containing many clustered formations.60 Presence of binucleate cells was an important criterion for the diagnosis of alveolar rhabdomyosarcoma.60
It was believed for a long time that desmin was a specific marker for RMS.28 However, desmin positivity has been seen in other members of SRCTs, while rhabdomyosarcoma can be positive for CD99.30,45,62 WT1 shows a strong cytoplasmic staining in rhabdomyosarcoma and a nuclear one in DSRCT, while is only focal in EWS/PNET. Unlike EWS/PNET positivity for cytokeratin, rhabdomyosarcoma is negative or show only a rare positive individual cell. Rare cases have been shown to express lymphoid markers including CD10, CD19 and CD20. Recently, more specific skeletal muscle markers have become available, including myogenin and MyoD1, and are highly sensitive in the diagnosis of rhabdomyosarcoma.59,63 These markers are expressed by positive nuclear staining. In challenging cases, molecular analysis shows a specific chromosomal aberration, t(2;13)(q35;q14) chromosomal translocation and/or the gene fusion transcripts PAX-FKHR in 80% alveolar subtype, but no specific translocation has been identified in the embryonal subtype.22,61,63
Rhabdoid tumors are easily confused with rhabdomyosarcoma. The presence of perinuclear cytoplasmic globular inclusions is usually more characteristic of rhabdoid tumors and eccentrically placed nuclei with a prominent central nucleoli. Hypercalcemia, and cytokeratin positive/desmin negative immunostaining, help in accurate tumor typing,19 although some cases can be desmin positive.21,22,61,64 Aspiration biopsies yield uniform-appearing, moderately sized neoplastic cells which are characterized by rounded contours, and solitary eccentric nuclei and uniform, intensely eosinophilic cytoplasm.61 The nuclei have thick nuclear membranes and a massive nucleolus. In contrast to rhabdomyosarcomas, these smears do not contain a spectrum of cellular appearances presenting different maturation stages of rhabdomyoblasts.
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