Cytomorphology of Some Uncommon Tumors of Childhood and Adolescence
U.R. Singh, K. Gupta, V.K. Arora, S. Gupta and A. Bhatia
Department of Pathology, University College of Medical Sciences and GTB Hospital, Shahdara, Delhi
Abstract. With the advent of newer adjuvant chemotheraputic regimes resulting in dramatic improvement in survival, it is mandatory to obtain quick correct diagnosis, which is provided by fine needle aspiration cytology (FNAC). Cytology of childhood tumors was studied to find any distinguishing features, which would help in arriving at a diagnosis.
Cytomorphology of 386 childhood and adolescent (0-19 years) tumors diagnosed between 1984 and 1993 were studied. Lipoma was the commonest benign tumor in 0-14 years age group. Fibroadenoma of the breast was the common benign tumor in adolescent (10-19 yrs) girls and pleomorphic adenoma in adolescent (15-19 yrs) boys. Wilms’ tumor was the most frequent solid malignant tumor in preschool children and Hodgkin lymphoma, mixed cellularity in the school going age (5-19 yrs). Malignant tumors were more frequent (199).
In addition, some rare malignancies like hepatoblastoma, meningioma, ganglioneuro- blastoma, adrenocortical carcinoma, clear cell sarcoma kidney and malignant histiocytosis were diagnosed. The cytological features and the differential diagnoses are discussed. It is possible to diagnose these uncommon tumors if particular attention is paid to the distinguishing cytomorphological features in correlation with clinicoradiological findings and cytochemistry (Indian J Pediatr 1996; 63 : 539647)
Key words : FNAC; Childhood; Tumors.
Tumors of infants, children and adoles- cents present a diagnostic challenge to the pathologists. Except for lymphomas, solid neoplasms common in adults are uncom- mon in childhood’. The dramatic improve- ment in the survival rate of children with malignancies on therapy requires that a quick and correct diagnosis be made at the earliest.
Triche2 emphasises the unique problem concerning the distinction between benign and malignant tumors in childhood. Dehn-
er3 describes the difficulties that can arise on histology in the differential diagnosis of small cell neoplasms. On cytology the dis- tinction between benign and malignant, and among the small cell neoplasms is even more difficult. Uncommon tumors of childhood and adolescence can also be di- agnosed on cytology as more and more ex- perience is gained and distinguishing cyto- morphological features become estab- lished.
We attempted to study the uncommon tumors with a view of finding any distin- guishing cytomorphological features which would help to differentiate these from the usual neoplasms encountered. The
Reprint requests: Dr. Arati Bhatia, Professor, Department of Pathology, University College of Medical Sciences & GTB Hospital, Shahdara, Delhi-110 095.
cytomorphological features and the differ- ential diagnosis of these unusual neo- plasms are discussed.
MATERIAL AND METHODS
Neoplasms in children aged 0 to 19 years aspirated over a ten year period (1984 to 1993) at University College of Medical Sci- ences, Delhi were reviewed.
Fine needle aspiration (FNA) was done using a 22-gauge needle and a 10 ml dis- posable syringe. Aspiration was done from a single site in tumors upto 3 cm and from multiple sites in larger tumors. Wet fixed and air dried smears were stained by Papanicolaou (PAP) and May Grunwald Giemsa (MGG) methods. If tissue frag- ments were obtained these were processed routinely for cell block and stained by H & E stains. Special stains like PAS, Mucicarmine and immunocytochemistry were done wherever necessary.
OBSERVATIONS
A total of 386 tumors were analysed during the last ten years. These could be classified as benign and malignant on their cytomorphologic features in 187 and 199
cases respectively (Tables 1 & 2).
Lipoma was the commonest benign tumor in the 0-14 years age group. Fibroadenoma breast was the common be- nign tumor in adolescent (10-19 yrs) girls and pleomorphic adenoma in adolescent (15-19 yrs) boys. Wilms’ tumor was the most frequent solid malignant tumor in preschool children and Hodgkin lymphoma (H.D.) mixed cellularity in the school going age (5-19 yrs). In children with benign neoplasm the male to female ratio was 1 : 1.8 and with malignant neo- plasm the ratio was 2 : 1. The cytomorphology of unusual childhood tumors seen in 10 cases is presented.
Adrenocortical carcinoma
A five-year-old male child was admitted with precocious puberty and a large (10 x 12 cm) firm mass in the right lumbar region. A soft to firm liver was palpable 12 cm below costal margin. Roentgenogram chest revealed multiple secondaries. Ultra- sound abdomen showed a right suprarenal mass and secondaries in liver.
FNA smears of suprarenal mass were moderately cellular. The cells were scat- tered singly or in small clusters. These were
| Tumors | 0-4 | 5-9 | 10-14 | 15-19 | Total | Histology |
|---|---|---|---|---|---|---|
| Lipoma | 5 | 4 | 5 | 11 | 25 | 4 |
| Neurofibroma | 1 | 3 | 2 | 3 | 9 | 3 |
| Haemangioma | 4 | 4 | 2 | 5 | 15 | 2 |
| Fibroadenoma | 0 | 0 | 2 | 81 | 83 | 33 |
| Pleomorphicladenoma | 0 | 0 | 0 | 14 | 14 | 7 |
| Miscellaneous | 9 | 4 | 9 | 19 | 41 | 2 |
| Total | 187 | 51 |
| Tumors | 0-4 | 5-9 | 10-14 | 15-19 | Total | Histology |
|---|---|---|---|---|---|---|
| Hodgkin disease | 0 | 21 | 17 | 12 | 50 | 11 |
| Non hodgkin lymphoma | 2 | 5 | 7 | 14 | 28 | 5 |
| Wilms' | 25 | 1 | 0 | 0 | 26 | 17 |
| Osteosarcoma · | 0 | 2 | 5 | 7 | 14 | 5 |
| Ewings | 1 | 1 | 6 | 6 | 14 | 3 |
| Neuroblastoma | 7 | 3 | 1 | 0 | 11 | 3 |
| Retinoblastoma | 5 | 2 | 0 | 0 | 7 | 3 |
| Miscellaneous | 12 | 4 | 7 | 26 | 49 | 18 |
| Total | 199 | 65 |
polyhedral to rounded cells with am- phophillic or dense blue cytoplasm and multinucleated giant cells. Some polyhe- dral cells showed giant bizarre nuclei with prominent nucleoli. Pleomorphism was marked and an occasional abnormal mito- sis was seen (Fig. 1). Based on the clinical history, cytomorphology and presence of secondaries liver, a diagnosis of adrenocor- tical carcinoma was made.
Meningloma
A 16-year-old male was referred for FNAC of a 2 x 2 cm painless, soft, left posterior au- ricular swelling of four years duration.
The aspirate was cellular with round to polygonal cells with moderate amount of cytoplasm and indistinct cell membranes, at places giving a syncytial appearance. Oc- casional nuclei showed intranuclear cyto- plasmic inclusions. also seen were concen- tric whorls of spindle cells and psammoma bodies (Fig. 2).
Hepatoblastoma
Three cases of Hepatobiastoma were
encounterd. One has been published else- where4.
Case Report 1 : An 18-month-old male child was admitted with abdominal lump, loss of appetite and weight. The child was anae- mic and had a firm liver lump extending to the right iliac fossa. Ultrasound examina- tion revealed the possibility of a primary malignancy of the right lobe of the liver.
The haemoglobin was 6.5 g/dl, total leukocyte count was 13.3 x 109/1. The pe- ripheral blood smear showed microcytic hypochromic anaemia. Serum bilirubin, se- rum aminotransferases and serum proteins were within normal limits. Serum alkaline phosphatase was 39 KA units per 100 ml.
The cytology smears were cellular with fragments of round to polygonal cells ar- ranged in cords or small acini (Fig. 3). The cells had a granular cytoplasm, hyperchro- matic nuclei and conspicious nucleoli. Prominent fatty change was seen in some clusters. Also seen were erythroblasts, my- elocytes, metamyelocytes and occasional megakarocyte.
Case Report 2 : A 3-year-old male child was admited with a 5 x 6 cm lump in right
hypochondrium for the last 6 months. UI- trasound showed a space occupying lesion in liver. The cytologic picture was similar to case 1 except for inconspicious extramedullary haematopoises. All three cases were of pure epithelial type.
Ganglioneuroblastoma
Case Report 1 : A 9-year-male was admitted with a progressively increasing lump abdo- men for four months. A 25 x 20 cm lump was palpable in left hypochondrium, umblical region extending into the left iliac fossa. Ultrasound examination revealed a soft tissue mass displacing the left kidney.
Case Report 2 : A 12-year-old male child was referred to FNAC clinic with progressively increasing abdominal mass for the last 1 year. The patient had loss of appetite and weight and was anaemic with a 5 x 3 cm firm lump in left lumbar region. CT scan showed a retroperitoneal extrarenal mass.
Case Report 3 : A six-month-old male child was admitted with a lump in abdomen of three months duration. The patient had weight loss and a hard 5 x 5 cm lump in the left lumbar region. Ultrasound and intrave- nous pyelography revealed a lateral dis- placement of left kidney by a, tumor of the left sympathetic chain.
The cytologic features in all three cases were similar. The smears were cellular with predominently small round cells having scant cytoplasm lying singly against a fibrillarv background. Occasionally rossette like structures were seen. Also seen were scattered large round polygonal cells with a single or multiple nuclei, prominent nu- cleoli and abundant blue cytoplasm
(Fig. 4). Histopathology confirmed the di- agnosis in case 3.
Clear cell sarcoma kidney (CCSK)
An 18-month-old male child was brought with a bimanually palpable, ballotable lump in the left lumbar region noticed since ten days. The ultrasound examination showed a homogenous mass in the middle and lower pole of left kidney with a well defined capsule. The upper pole was hydronephrotic. Liver, spleen and right kidney were normal. FNA diagnosis of a small cell tumor was made. Nephrectomy was done and diagnosed as clear cell sarco- ma kidney.
The patient had a recurrence of two years after nephrectomy. The recurrence was seen as a 3 x 3 cm hard nodule, fixed to the skin at the site of previous operation scar. A repeat FNAC was performed.
The aspirate from the left lumbar region was cellular with monomorphic population of polyhedral to round single cells. The cy- toplasm was moderate with rounded nu- clei eccentrically placed in some cells show- ing fine granular chromatin and 1-2 incon- spicuous nucleoli (Fig. 5). The cell bounda- ries were indistinct. Occasional mitosis was seen. There were highly cellular clusters of cells arranged around a capiliary network and also present was extra cellular mucoid material. Nuclear groove was seen in a fair number of cells. Cytoplasmic vaculoes were seen in few cells.
On histology a diagnosis of clear cell sar- coma was made. Smears from recurrent nodule showed similar morphology except for increased mitotic figures. Histology of the recurrent nodule showed neurilemmo- ma like nuclear palisading (Fig. 6).
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Malignant histiocytosis (MH)
A ten-year-old male was admitted with the complaints of high grade intermittent fe- ver, breathlessness, weight loss and pallor of one months duration. On examination there were bilateral discreet cervical and axillary lymph nodes 0.5 to 1 cm in size and 0.5 to 2 cm subcutaneous swellings over the back and both upper limbs. There was mild hepatosplenomegaly and bilateral crepitations in the chest.
The haematological investigations re- vealed haemoglobin of 9.5 g/dl and leuko- cytosis (20.5 x 109/L) with neutrophilia. Piatelet count was normal. Bone marrow a. pirate revealed erythroid hyperplasia without atypical cells. The widal and man- trux tests were negative. X-ray chest showed mediastinal widening with a tra- cheal shift to the right.
FNA smears from both cervical lymphnode and subcutaneous nodule back revealed cellular smears of pleomorphic
cells with deep blue cytoplasm and multi- ple vacuolations and outpouchings. The nucleus was large with lacy chromatin oc- cupying most of the cell and inconspicuous nucleoli (Fig. 7). The smears revealed a spectrum of histiocytic cells ranging from relatively benign to frankly malignant cells. Erythrophagocytosis was observed only in an occasional differentiated histiocyte. A repeat FNA to carry out cytochemical stain- ing was done from the cervical lymphnode and the smears were fixed in citrate-ac- etone-methanol. Non specific estearase (al- pha napthyl acetate esterase (ANAE) and acid phosphatase (AP) were both diffusely positive.
DISCUSSION
After the initial skepticism and hesitancy FNAC is now here to stay with more and more clinicians accepting this procedure in India. However, there are only a few re- ports of childhood and even fewer of ado- lescent tumors from India. These tumors are a diagnostic dilemma3. In children the dividing line between benign and malig- nant tumors is very thin2. Cytomorphology of some uncommon tumors and their dif- ferential diagnosis is reported as the cytol- ogy and the pit falls encountered in the di- agnosis of common tumors is well known.
We encountered malignant neoplasms more frequently as these were rapidly growing and symptomatic. In the west, central nervous system tumor, followed by lymphoma are the commonest solid neo- plasms in childhoods. A previous study from India’ found Non-Hodgkin lymphoma as the commonest childhood tumor. We however, found Hodgkin’s lymphoma (H.D) as the most frequent tumor. Stiller5 postulates that such a high
incidence of H.D. in young children in many developing countries was linked to the poor socio-economic conditions. In this study we found benign neoplasms more among girls while the malignant tumors were more among boys.
Adrenocortical carcinoma is a rare ma- lignant tumor. Pediatric adrenal tumors with a size greater than 3.5 cm is consid- ered as a predictor of malignant behav- iour7. In the present case the tumor was large with abnormal mitosis, cellular atypia and secondaries in lung and liver.
An attempt to differentiate adrenocorti- cal hyperplasia and carcinoma has been made on the tumor size, cellularity, pleo- morphism and mitosis8. But none of these features are absolute and only the presence of secondaries is a distinctive feature of malignancy.
The cytological diagnosis of meningi- oma does not pose a problem in the pres- ence of syncytial cell whorls and psammo- ma bodies. If psammoma bodies predomi- nate, metastatic papillary carcinoma of thy- roid must be excluded by the absence of features like papillary fragments nuclear groove and intranuclear inclusion. Despite the presence of intranuclear inclusions the syncytial whorls and psammoma bodies fa- voured the diagnosis of meningioma in our case.
Three children all below the age of four years were diagnosed as Hepatoblastoma. A pure epithelial tumor with predomi- nance of fetal hepatocytes and extra-med- ullary haematopoieses was seen in all three cases. Hepatocellular carcinoma is distin- guished from hepatoblastoma by the pres- ence of cells larger than normal hepatocytes, broad trabeculae, consider- able nuclear prominance, tumor giant cells, absence of hematopoises and accompany-
ing cirrhosis9. Tumors with pure fetal his- tology are associated with a better survival than other histological types as also ab- sence of mitosis andpresence of differenti- ated mesenchymal elements10.
Ganglioneuroblastoma was encountered in three cases. All patients were males and the age ranged from 6 months to 12 years. Most of the patients of ganglio- neuroblastoma present with weakness, loss of weight and a palpable abdominal mass” 15.
A fine fibrillar cobweb of neurils ema- nating from neoplastic cells is an important diagnostic feature in the less well differen- tiated tumors16. Controversy exists on the presence of Homer Wright rosettes on cy- tology smears13-15. These rosettes were ab- sent in our cases. However, the presence of fibrillar background and ganglion cells es- tablished the diagnosis of ganglioneurob. lastoma.
The prognosis of ganglioneuroblastoma like that of neuroblastoma is related to the age of onset and is most favourable in chil- dren 3 years and younger. Patients with tu- mor in extra abdominal locations tend to have a better prognosis11,12. All three pa- tients had intra abdominal ganglioneurob- lastoma, two arising in the adrenal and one from the sympathetic chain. Contrary to the views of earlier workers we feel it is not possible to classify ganglineuroblastoma into diffuse and composite type on cytolo- gy.
Clear cell sarcoma of kidney was en- countered in a single case (CCSK). CCSK must be differentiated from Wilms’ where in addition to clusters of small round cells, tubular structures and mesenchymal cells are seen. In CCSK the cells are larger with moderate pale cytoplasm and eccentrically placed nuclei showing fine granular chro-
matin. One to two inconspicuous nucleoli with nuclear groove in seen17.18. Renal neu- roblastoma and rhabdoid tumor can be eas- ily differentiated by the presence of multi- ple layers of cells forming psuedo rosettes and tumor cells with abundant acidophilic cytoplasm without striations and promi- nent nucleoli19. The prognosis of this tumor is considered dismal. CCSK is highly ma- lignant with a predisposition to bone me- tastasis and a high rate of relapse20,21. Our patient had a local recurrence two years af- ter nephrectomy and chemotherapy.
Malignant histicytosis (MH) is a rare ag- gressive neoplasm of true histiocytes that affects children and adults. MH was de- scribed by Rappaport as a systemic pro- gressive invasive proliferation of morpho- logically atypical histiocytes and their pre- cursors22.
Fever, lymphadenopathy and hepat- osplenomegaly are the usual presenting features23. Cytological and histological ex- amination show polymorphic histiocytic cells in various stages of differentiation with blasts predominating. Malignant histi- ocytosis cells react positively with acid phosphatase (AP), alpha-naphthyal acetate esterase (ANAE), alpha-anti chymot- rypsin24 and antibodies directed against EMA, HLA, CD 30 etc25. The main differen- tial diagnosis of MH is with,large cell ana- plastic (Ki-1) lymphoma (LCAL). LCAL is a localizied lesion with immunoblasts like large cells with abundant grey cytoplasm showing focal positivity with AP and ANAES. MH is a diffuse disease with the histocytic cells showing a distinct ba- sophilic cytoplasm and diffuse positivity with AP and ANAE”. Haemophagocytic syndromes should be excluded by investi- gating for microbiologic causes and drug ingestionª. The histiocytes in haemophago-
cytic syndrome are mature with low nucle- ar cytoplasmic ratio, inconspicuous nucleo- li and abundant non basophilic cyto- plasm23.
CONCLUSIONS
With the new treatment regimes and newer chemotherapeutics offering a near total cure, it is mandatory that a quick, correct diagnosis be provided to the treating physi- cian. FNAC is now an accepted procedure in the diagnosis of common lesions of childhood and adolescence. The uncom- mon lesions of childhood and adolescence can also be diagnosed on cytology if partic- ular attention is paid to the cytomorpholo- gy, clinical data and radiological findings. Adrenocortical carcinoma, meningioma and ganglioneuroblastoma can be diag- nosed with ease on FNAC. CCSK can be differentiated from Wilms’ if particular at- tention is paid on cell size and nuclear grooves. A clinico-cytologic diagnosis of MH can be made when immunocytochem- istry is positive.
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