ACTA CYTOLOGICA 0001-5547/10/5402-0142/$21.00/0 © The International Academy of Cytology142

Objective

To present and discuss our experience with cytologic study offine needle aspiration for the diagnosis of histologically con-firmed childhood teratomas/teratoid lesions and to highlightthe limitations in diagnosis.

Study Design

Cases with histologic diagnosisof teratoma from the archivesof the histopathology section ofthe Department of Pathologywere identified. Only casespreceded by fine needle aspira-tion cytology were included inthe study.

Results

The 11 cases of teratoma/teratoid lesions were from 4 malesand 7 females. Their ages ranged from 3 months to 12 years(mean, ~3 years). The clinicoradiologic diagnosis varied be-tween neuroblastoma, Wilms tumor and teratomas. Theradiologic features were available in only 6 cases at the timeof aspiration. Squamous cells were the main findings incases diagnosed as teratomas. Other elements, like neuroec-todermal cells amd mesodermal derivatives like muscle, adi-pose tissue and columnar cells, were also seen. Immaturemesenchymal fragments were recognized in 2 cases.

Conclusion

Clinical details and radiologic investigations are crucial tothe cytologic diagnosis of teratomas, differentiating them

from the other common childhood tumors. (Acta Cytol2010;54:142–147)

Keywords: aspiration biopsy, fine-needle; childhood;teratomas.

Tumors in children areas diverse as those in

the adults and present anumber of challenges forthe pathologist. Reports onadult tumors usually in-clude categories classifiedby topographic sites. Ex-cept for those in the brain,

tumors in children are invariably classified by histo-logic type rather than their anatomic site, as the prog-nosis depends on the former.1

When tissues from primordial germ cell layers (ecto-derm, endoderm and mesoderm) are present in a tu-mor in an organoid fashion, it qualifies as a teratoma.Sacrococcygeal area is the most frequent site in infancy,accounting for 1 in 35,000–40,000 births.2 The ovaryaccounts for 30% of teratomatous germ cell neoplasiain children, while in the testis 33% of all tumors areteratomas. Among neonates, they are known to con-stitute 25–35% of all cases. The majority of teratomasin infancy and childhood are benign. The maturity orimmaturity of the teratomatous elements is an impor-tant determinant of prognosis, in addition to the pres-ence of other less favorable germ cell components,

A combined diagnostic approach ofclinical details, biochemical markers,radiologic investigations and FNAC

is advisable....

Limitations in the Diagnosis of ChildhoodTeratoid Lesions on Fine Needle AspirationCytology

Sonal Sharma, M.D., and Kiran Mishra, M.D.

From the Department of Pathology, University College of Medical Sciences, Delhi, India.

Dr. Sharma is Reader.

Dr. Mishra is Professor.

Address correspondence to: Sonal Sharma, M.D., Department of Pathology, University College of Medical Sciences, Shahdara, Delhi-110095,India (sonald76@rediffmail.com).

Financial Disclosure: The authors have no connection to any companies or products mentioned in this article.

Received for publication August 6, 2008.

Accepted for publication September 25, 2008.

Fine Needle Aspiration

143

Childhood Teratoid Lesions

Volume 54 Number 2 March–April 2010 ACTA CYTOLOGICA

such as embryonal carcinoma, endodermal sinus tu-mor and dysgerminoma/seminoma. A thorough path-ologic examination of a large germ cell tumor is ob-viously of paramount importance in order to ascertainthe different elements both quantitatively and qualita-tively. Accurate diagnosis is established with histologicexamination of the tumor, clinical assessment of thepatient and use of tumor markers like α-fetoprotein(AFP) and β–human chorionic gonadotropin.3

Although teratomas form an important group of tu-mors in children, experience with cytologic diagnosisfrom fine needle aspirates of tumor tissues of ter-atomas is limited. There is a paucity of comprehensivestudies on the cytomorphology of teratomas. The fewreports in the literature are passing references or ascase reports. A preoperative diagnosis of teratomas isof immense help to the treating surgeon. In this studywe analyzed the fine needle aspiration cytology(FNAC) features of teratomas occurring at differentsites in children and discussed the limitations and pit-falls in its diagnosis.

Materials and Methods

Patients and Diagnosis

Through a comprehensive search, cases with a histo-logic diagnosis of teratoma/teratoid lesions in the agegroup of 0–16 years were identified from the archivesof the histopathology section of the Department ofPathology. Only cases preceded by FNAC were in-cluded in the study. A retrospective review of clinicalcharts, radiologic data and evaluation of cytologicsmears was done.

Fine Needle Aspiration Cytology

All FNACs were performed percutaneously with orwithout sonographic guidance, depending on the siteof aspiration. The cytologic material was obtainedfrom multiple sites (at least 2 or 3) using a 23-gaugeneedle. The aspirates obtained were immediately usedfor preparation of air-dried smears and smears for Pa-panicolaou stain. The air-dried smears were stainedwith May-Grünwald-Giemsa stain. Smears for Papa-nicolaou stain were immediately immersed into 95%alcohol.

Histopathology

The tissue specimens obtained were fixed in 10%buffered formalin, processed in a routine manner andembedded in paraffin. Sections were cut and stainedwith hematoxylin and eosin.

Results

The 11 cases of teratoid lesions were from 4 males and7 females. Their ages ranged from 3 months to 12years (mean, ~3). Sites of aspiration included retroperi-toneum (6), lower abdomen, (ovary) (3), epigastric(stomach) (1), and sacrococcygeal (1). The clinical de-tails along with cytohistologic diagnosis are given inTable I. Seven of the 11 patients were 2 years of age oryounger; 4 were in the first year of life. The remaining4 were between 6 and 12 years of age. There was a fe-male preponderance, the ratio being 1.75:1. The clini-coradiologic diagnosis varied between neuroblastoma,Wilms tumor and teratomas. The radiologic featureswere available in only 6 cases at the time of aspiration.

Table I Clinicoradiologic Features of Teratomas

Case no. Age/sex Clinical findings Cytologic diagnosis Histologic diagnosis

1 3 mo/M Lump left lumbar and umbilical Mature teratoma Mature teratoma, stomach

region, H/o hematemesis +,

5 × 5 cm

2 3 mo/M Lump abdomen with vomiting, Teratoma Immature teratoma, retroperi-

6 × 5 cm toneum

3 9 mo/F Retroperitoneal mass, 10 × 8 cm Neuroblastoma Immature teratoma, retroperi-

toneum

4 1.5 yr/F Mass left iliac fossa, 7 × 7 cm Possibly mature cystic teratoma Immature teratoma, ovary

5 2 yr/M Mass right upper quadrant abdo- Teratoid hepatoblastoma/ terato- Mixed germ cell tumor

men, 10 × 8 cm carcinoma

6 6 yr/F Epigastric lump, 6 × 6 cm Teratoma, intraabdominal Mature teratoma, mesenteric

7 6 yr/F Sacrococcygeal swelling, excised Endodermal sinus tumor Mixed germ cell tumor (immature

twice, recurrence teratomas+ EST+ embryonal

carcinoma)

8 9 yr/F Left lower abdominal lump, Teratoma with ?malignancy Immature teratoma

12 × 10 cm

9 2 yr/F Mass abdomen, 7 × 3 cm Endodermal sinus tumor Mixed germ cell tumor (mature

teratomas+ EST)

10 1.5 yr/M Lump left lumbar region, 8 × 7 cm Immature teratoma Teratoid Wilms tumor

11 4 mo/F Lump right lumbar region, 8 × 6 cm Teratoma/teratoid Wilms tumor Fetus-in-fetu

EST = endodermal sinus tumor, H/o = history of.

144

Sharma and Mishra

ACTA CYTOLOGICA Volume 54 Number 2 March–April 2010

Cytologic Findings

Aspiration yielded either fluid or blood-mixed parti-cles in most of the cases. The cytology smears werepaucicellular in cases where fluid was aspirated andmoderately cellular in blood-mixed aspirates. In caseswith a fluid background, degeneration and presence ofinflammatory cells was a common feature. Squamouscells were the main findings in cases diagnosed as ter-atomas. Other elements, like neuroectodermal cellsand mesodermal derivatives like muscle, adipose tissueand columnar cells, were also seen. The feature thathelped the most in arriving at a diagnosis was the ad-mixture of a heterogeneous population of cells.

A BFigure 1 (A) Case 1. Cytologic preparation of mature teratoma showing numerous squamous cells in a fluid background. Other smears

showed skeletal muscle (upper inset) and columnar ciliated cells (lower inset). (B) Section from mature teratoma showing columnar

epithelium–lined glands, mature cartilage and bone (A, May-Grünwald-Giemsa stain, × 100; B, hematoxylin-eosin, × 40).

Figure 2 (A) Case 3. Cytologic smears from showing clusters of round cells with rosette formation and neuroblasts only. (B) Section from

the same tumor showing multiple foci of immature neural tissue (neuroblasts and neural canals) intermixed with mature elements

(A, May-Grünwald-Giemsa stain, × 200; B, hematoxylin-eosin, × 40).

A

Both mature teratomas showed abundant squamouscells, columnar cells and mesenchymal fragments withadipose tissue or skeletal muscle fibers (Figure 1). Ofthe 4 histologically proven immature teratomas, 3could be diagnosed as teratomas on cytology owing toa similar heterogeneous cell population as in matureteratomas. Atypical cells could be seen in 3/4 cases. In1 case, due to a preponderance of atypical neuroecto-dermal cells, a diagnosis of neuroblastoma was given(Figure 2). All 3 mixed germ cell tumors could be di-agnosed as malignant germ cell tumors, although in 2cases only an endodermal sinus component could beappreciated (Figure 3). The heterogeneous cells along

B

145

Childhood Teratoid Lesions

Volume 54 Number 2 March–April 2010 ACTA CYTOLOGICA

with endodermal sinus component in the third casehelped in offering a diagnosis of malignant teratoma.One case of teratoid Wilms tumor was wrongly diag-nosed as immature teratoma, owing to a heteroge-neous population of squamous cells, smooth muscle,skeletal muscle and fat. The small round cell (blaste-mal) component was thought to be neuroectodermalon cytology. A case of fetus-in-fetu was also misinter-preted as teratoma/teratoid Wilms tumor on cytology.Table II presents various diagnostic cytologic vari-ables in teratomas along with the histologic and cyto-logic diagnosis of the 11 cases.

Discussion

Teratomas illustrate the relationship of histologic ma-turity to biologic behavior. They may occur as benign,

well-differentiated cystic lesions (mature teratomas),as lesions of indeterminate potential (immature ter-atomas) or as unequivocally malignant teratomas (usu-ally admixed with another germ cell tumor compo-nent, such as endodermal sinus tumor). They exhibit 2peaks in incidence: the first at approximately 2 years ofage and the second in late adolescence or young adult-hood. The first peak represents congenital neoplasms;the later-occurring lesions may also be of prenatal ori-gin but are more slowly growing. Although sacrococ-cygeal teratomas are the most common teratomas ofchildhood, accounting for 40% or more of cases, weexperienced only a single case in our study. Approxi-mately 75% of these tumors are mature teratomas,and about 12% are unequivocally malignant andlethal. The remainder are immature teratomas, and

A BFigure 3 (A) Case 7. Aspirate from mixed germ cell tumor showing malignant cells with marked pleomorphism and prominent nucleoli (inset)

and numerous teratoid bodies (arrow). (B) Section from the same case showing yolk sac elements surrounded by immature mesenchyme. Inset:

other areas showed mature elements, too (A, May-Grünwald-Giemsa stain; B, hematoxylin-eosin; A and B, × 200).

Table II Cytologic Features of Teratomas

Immature elements/

CaseMature elements malignant components

no. Squamous Columnar Fat/stroma Smooth muscle Others Neural Others Diagnosis

1 + + − + − − − Mature teratoma

2 + + + − − − − Mature teratoma

3 + + + + − − − Teratoma

4 + + − − − + − Mature teratoma

5 − − − − − + − Neuroblastoma

6 + + + − − + − Immature teratoma

7 − − − − − − EST EST

8 − − − − − − EST EST

9 + + + + − − Atypical Teratoid hepatoblas-

cells + toma/teratocar-

cinoma

10 + − + + Skeletal muscle + + − Immature teratoma

11 − − + + Skeletal muscle + + − Teratoma

EST = endodermal sinus tumor.

their malignant potential correlates with the amountof immature tissue, usually immature neuroepithelialelements, present. Most of the benign teratomas areencountered in younger infants (< 4 months), whereaschildren with malignant lesions tend to be somewhatolder. Other sites for teratomas in childhood includethe testis, ovaries and various midline locations, suchas the mediastinum, retroperitoneum, and head andneck.4 Although extragonadal teratomas are uncom-mon, they need to be considered in FNAC materialfrom midline mass lesions. They are academically in-teresting because of the biologic diversity exhibited bytheir components.

Few studies on cytologic features of teratomas havedocumented the presence of numerous superficial andanucleated squamous cells, glial tissue, or columnarand ciliated cells within a mucoid or fluid back-ground.5-14 In our study, the benign and immatureteratomas usually yielded fluid and scant cellularitycomposed invariably of squamous cells and glandularepithelium, respiratory epithelium and mesenchymalelements like adipose tissue. The presence of squa-mous cells in the smear with adipose tissue, skeletaland smooth muscle, and columnar cells made us thinkalong the lines of teratomas. Thus, a heterogeneouscell population in the aspirated smear was the diag-nostic feature of teratomas in this study.

Radiology studies were available in 6 cases. In 5 ofthese 6 cases, the cytologic findings were consistentwith teratoma. The sixth case, immature teratoma,was diagnosed as neuroblastoma due to aspiration ofimmature elements—i.e., neuroblasts only. Radiolog-ic and clinical details specifically about the site of ori-gin of the tumor, when combined with cytology, canhelp to establish the diagnosis of teratomas. TeratoidWilms tumor in our study was diagnosed as teratomaon cytology as radiology was not available at the timeof fine needle aspiration. Fetus-in-fetu was anothercase that mimicked teratoma cytologically because ofthe presence of a heterogeneous cell population. Apost-FNAC ultrasonogram revealed a retroperitonealmass with a vertebral axis and unique vascular pattern,thus clinching the diagnosis. Thus, supplementaryfindings of radiologic investigations help a great dealin arriving at a correct diagnosis.

Immature teratomas have neuroblasts and primitivemesenchymal fragments along with other mature ele-ments. Morimura et al6 described glial tissue withsmall round cells (neuroblasts) forming rosettelikestructures in the aspiration smears of immature ter-atomas. The present study also had similar findings incases of immature teratomas, which were misinter-preted as neuroblastoma and malignancy in 2 cases.

Few cases of malignant teratomas with variegatedappearance dominated by malignant components like

146

Sharma and Mishra

ACTA CYTOLOGICA Volume 54 Number 2 March–April 2010

embryonal carcinoma, undifferentiated carcinoma,adenocarcinoma and malignant mesenchymal compo-nents have been described on cytology.10-13 We en-countered 3 cases of teratomas associated with malig-nant mixed germ cell elements. In 2 of 3 cases, onlythe endodermal sinus tumor component was recog-nized on cytology. In 1 case, teratomatous elementsand malignant elements of endodermal sinus tumorwere identified. Thus, we suggest thorough samplingin cases suspected of germ cell origin by multiple siteaspiration, as the teratoma component needs surgicalintervention. Treatment of such mixed tumors bychemotherapy alone will eradicate the malignant ele-ments and leave the mature diploid teratomas intact;they can continue to grow and present later withgrowing teratoma syndrome.15

Teratoid lesions could be correctly diagnosed in 8of 11 cases by cytology in our study, while classifyingthem into immature category was possible in just 1case. Malignant mixed germ cell tumors were pickedup in all 3 cases, though all components could not beidentified on cytology. Chao et al5 also experienceddifficulty in establishing the diagnosis of immatureteratoma and mixed germ cell tumors by cytology un-less various cell types were identified. Motoyama etal8 found cytologic findings to be variable accordingto the site aspirated even within the same tumor. Wealso faced similar problems. An immature teratomawas diagnosed as neuroblastoma because of the pres-ence of neuroectodermal cells. Aspiration from multi-ple sites helps to overcome these problems.

Other problems in diagnosis include granuloma-tous reaction to tumor, sampling error and problemsin differentiating from well-differentiated squamouscell carcinoma. Teratomas may contain extensive cys-tic or hyalinized, acelluar areas, making it difficult toobtain a sufficient number of neoplastic cells by fineneedle aspiration.

The use of fine needle aspiration in diagnosing cys-tic teratomas has been shown to be effective and valu-able. Cytology can help to diagnose clinically unsus-pected teratomas from other common abdominalchildhood tumors like neuroblastoma, Wilms tumorand lymphoma. All these tumors lack the admixture ofvarious types of cells on the cytology smear as seenclassically in teratomas.

The prognosis of teratomas is far better than theabove common childhood tumors. The majority ofteratomas in infancy and childhood are benign. In areview of 68 cases Valdiserri et al16 found 75% be-nign, 11.8% immature and 13.2% malignant tera-tomas. Schropp et al2 found 22% malignant and 78%benign teratomas in their study of 73 cases. Amongthe pediatric population, there is a tendency towardsdevelopment of malignant teratomas with increasing

147

Childhood Teratoid Lesions

Volume 54 Number 2 March–April 2010 ACTA CYTOLOGICA

age.2,17 The amount of immature tissue, especially theneuroepithelial component, is central to pathologicgrading, which correlates with the management andprognosis. Also, the age at diagnosis, anatomic site anddegree of maturation of the primary tumor correlateswith the clinical behavior. During neonatal period andinfancy, even immature teratomas and malignantmixed germ cell tumors rarely manifest aggressive be-havior.18 The suspicion of immature/malignant ele-ments in teratomas can be supplemented by serumstudies like vanillyl mandelic acid), β–human chorion-ic gonadotropin and AFP. Therefore, it is importantto differentiate these tumors preoperatively fromother childhood tumors that follow malignant course.

In conclusion, a combined diagnostic approach ofclinical details, biochemical markers, radiologic inves-tigations and FNAC is advisable for a correct preop-erative diagnosis of teratomas/teratoid lesions andtheir effective management.

References

1. Gurney JG, Richmond KS, Scott D, Lesie LR: Incidence ofcancer in children in the United States. Cancer. 1995;75:2186–2195

2. Schropp KP, Lobe TE, Rao B, Mutabagani K, Kay GA,Gilchrist BF, Philippe PG, Boles ET Jr: Sacrococcygeal ter-atoma: The experience of four decades. J Pediatr Surg 1992;27:1075–1079

3. Dehner LP: Soft tissue, peritoneum and retroperitoneum. InPediatric Surgical Pathology. Edited by T Grayson. Baltimore,Williams & Wilkins, 1987, pp 918–924

4. Maitra A, Kumar V: Diseases of infancy and childhood. In Rob-bins & Cotran Pathologic Basis of Diseases. Edited by V Kumar,AK Abbas, N Fausto. Philadelphia, Saunders, 2004, pp 498–499

5. Chao TY, Nieh S, Huang SH, Lee WH: Cytology of fine nee-dle aspirates of primary extragonadal germ cell tumors. Acta

Cytol 1997;41:497–503

6. Morimura T, Hoshi K, Ishida T, Endo C, Sato A: Cytology ofa fetal immature teratoma: Intrauterine aspiration for prenataldiagnosis. Acta Cytol 1997;41:1240–1241

7. Ganjei P: Fine needle aspiration cytology of the ovary. Clin LabMed 1995;15:705–726

8. Motoyama T, Yamamoto O, Iwamoto H, Watanabe H: Fineneedle aspiration cytology of primary mediastinal germ cell tu-mors. Acta Cytol 1995;39:725–732

9. Das DK, Pant CS, Rath B, Prakash S, James T, Sodhani P: Fineneedle aspiration diagnosis of intra-thoracic and intra-abdomi-nal lesions: Review of experience in pediatric age group. DiagnCytopathol 1993;9:383–393

10. Akhtar M, Dayel FA: Is it feasible to diagnose germ cell tumorby fine needle aspiration biopsy? Diagn Cytopathol 1997;16:72–77

11. Balslev E, Frances D, Jacobson GK: Testicular germ cell tu-mors. Acta Cytol 1990;34:690–694

12. Highman WJ, Oliver RTD: Diagnosis of metastasis from tes-ticular germ cell tumors using fine needle aspiration cytology. J Clin Pathol 1987;40:1324–1333

13. Collins K, Geisinger KR, Wakely PE, Olympio G, SilvermanJF: Extragonadal germ cell tumors: A fine needle aspirationbiopsy study. Diagn Cytopathol 1995;12:223–229

14. Schwartz MR, Rapp ME, Rybak LP, Gillespie JJ: Fine needleaspiration diagnosis of a nasopharyngeal teratoma. Acta Cytol1991;35:360–364

15. Logothetics CJ, Samuels ML, Trindade A: The growing ter-atoma syndrome. Cancer 1982;50:1629–1635

16. Valdiserri RO, Yunis EJ: Sacrococcygeal teratoma: A review of68 cases. Cancer 1981;48:217–221

17. Miles RM, Stewart GS Jr: Sacrococcygeal teratomas in adults.Ann Surg 1974;179:676–683

18. Dehner LP: Gonadal and extragonadal germ cell neoplasm:Teratomas in childhood. In Pathology of Neoplasia in Childrenand Adolescents. Edited by M Finegold. Philadelphia, Saun-ders, 1986, pp 282–312