 Abstract | | |
Sacrococcygeal yolk sac tumor is an uncommon pediatric neoplasm. It usually presents with intra-abdominal or gluteal pain and mass. At later stage, it disseminates to regional nodes and distant organs. We describe one such neoplasm in an 18-month-old male child who turned symptomatic with multiple bilateral lung metastases. The tumor produced the least deformity to his physique, to become detectable on routine inspection and clinical examination. Finally, a combined approach through clinical, radiological, pathological, and biochemical perspectives established the diagnosis.
Keywords: Alpha-fetoprotein, germ cell tumor, lung metastasis, sacrococcygeal region, yolk sac tumor
How to cite this article:
Mondal K, Mandal R. Bilateral lung metastases unveils an asymptomatic sacrococcygeal yolk sac tumor. Indian J Pathol Microbiol 2017;60:565-7 |
| Introduction | |  |
Primary extragonadal germ cell tumors (EGCTs) represent 2%–5% of all germ cell tumors (GCTs). Sacrococcygeal region and brain are its predominant locations.[1],[2] Sacrococcygeal GCTs generally manifest with an external mass, attached to the sacrum and coccyx. Rarely, it remains entirely confined to the pelvis. Yolk sac tumor (YST) is the most common malignant GCT in the sacrococcygeal region and the second most prevalent pediatric EGCT following teratomas.[3] YSTs frequently metastasize to liver and lungs. However, a symptomatic YST at metastatic sites without any mass effect at its origin is extremely unusual.[1] In this report, we describe a primary sacrococcygeal YST in an 18-month-old child, who presented with maiden respiratory symptoms from bilateral lung metastases.
| Case Report | | |
A 1½-year-old child, who was suffering from fever, cough, and breathlessness for 2 weeks, was brought to the pediatric medicine outdoor. Contrast-enhanced computed tomography (CECT) of his thorax visualized multiple hyperechoic nodules in both lung fields [Figure 1]a. It indicated bilateral metastatic lung disease. | Figure 1: Sacrococcygeal germ cell tumor: Multiple bilateral lung metastases on contrast-enhanced computed tomography thorax (a); clinically, mildly bulged supragluteal part of buttock (b); on contrast-enhanced computed tomography abdomen, large irregular heterogeneous mass in the presacral region (c)
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Clinically, there was no obvious organomegaly. Both his testes appeared unremarkable. However, his supragluteal portion of the buttock was faintly bulged [Figure 1]b. Abdominopelvic CECT demonstrated a large irregular mass in the presacral region that insinuated beneath the vertebral column to produce a soft tissue eminence [Figure 1]c. The entire clinico-radiological scenario indicated an Altman Type III sacrococcygeal tumor. CT-guided fine needle aspiration cytology was performed from the mass.
Microscopically, the smears were hypercellular. It exhibited undifferentiated large neoplastic cells in the microglandular and papillary clusters, which often simulated “glomeruloid” structures. The tumor cells contained round-to-ovoid nuclei with prominent nucleoli and abundant vacuolated cytoplasm with indistinct cell borders [Figure 2]a and [Figure 2]b. Considering the child's age and radio-cytological presentation, a diagnosis of primary sacrococcygeal GCT was provisionally suggested. | Figure 2: Sacrococcygeal yolk sac tumor: Cytologically papillary clusters (a: MGG stain, ×40), and “glomeruloid” structures (a, inset: MGG stain, ×100) of undifferentiated tumor cells exhibiting prominent nucleoli and abundant vacuolated cytoplasm (b: MGG stain, ×1000). Histologically, reticular-microcystic architecture (c: H and E stain, ×40), Schiller-Duval bodies and hyaline (arrowheads) globules (d: H and E stain, ×100)
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The serum α-fetoprotein (AFP) was high at 9322 ng/ml (normal: <7 ng/ml) as was the lactate dehydrogenase (LDH) level (610 IU/l, normal: 120–300 IU/l). However, the β-human chorionic gonadotropin (β-hCG) and liver function test results lingered within normal limits. The sacrococcygeal mass was debulked. On histopathology, the neoplastic cells were exclusively arranged in reticular-microcystic and pseudoglandular architecture, with characteristic Schiller-Duval bodies and hyaline globules [Figure 2]c and [Figure 2]d. Biopsy of the lung nodules reciprocated identical histomorphology. Finally, reminding the overall clinical, radiological, pathological, and serological features, the neoplasm was diagnosed as primary sacrococcygeal YST with bilateral pulmonary metastases. Postoperatively, the child was instituted upon adjuvant chemotherapy. However, unfortunately, he breathed his last during the fourth cycle.
| Discussion | | |
GCTs comprise a group of neoplasms originating from primitive germ cells located in the gonads and other midline extragonadal sites from brain to sacrococcygeal region.[3] Among children, the primary GCTs arise in ovary (26%), sacrococcygeal area (24%), testis (18%), brain (18%), mediastinum (4%), retroperitoneum (4%), and vagina (2%).[1] Rare sites include the heart, pleura, pharynx, base of the skull, upper jaw, liver, alimentary tract, and subcutaneous tissue.[3]
Malignant GCTs account for 2%–3% of all pediatric cancers. Pure YST involving the testis (42.6%) and ovary (32.6%) receives its dominant share.[4] Altman et al. classified the sacrococcygeal GCTs into four types according to its externalized/internalized component: Type I – exclusively external, Type II – predominantly external minimally internal/intrapelvic, Type III – predominantly presacral/abdominopelvic minimally external, and Type IV – exclusively presacral/intrapelvic. Type I (47%) and II are the most common variants. Malignancy is highest associated with Type IV tumors and the least with Type I.[5] According to this classification, the discussed tumor was categorized as an Altman Type III tumor.
Patients with predominantly intrapelvic tumors complain about constipation, dysuria, palpable mass, and pain. These tumors are often detected late with exaggerated local involvement and metastasis to regional nodes or distant organs. However, a symptomatic EGCT only at its metastatic site, without any appreciable deformity at its origin, has seldom been described in literature.[6] The currently reported patient manifested with respiratory difficulties. It was caused by pulmonary metastatic disease disseminating from a sacrococcygeal malignancy. That primary neoplasm did not produce any significant mass effect or deformity, except an ill-defined bosselated appearance to his lower back. The overall clinico-radiological, pathological, and serological features of the child were implicitly assessed. It yielded the confident diagnosis of primary sacrococcygeal YST with bilateral lung metastases.
The serological markers for GCTs include AFP, β-hCG, and LDH. High β-hCG level is diagnostic of choriocarcinoma. LDH is nonspecifically raised >200 IU/l in 50% GCTs. However, higher levels favor nonseminomatous EGCTs.[7] AFP is the specific tumor marker for pure YST and also the YST component of mixed GCT. It is particularly helpful for diagnosing extragonadal YSTs. An excessively high AFP in the absence of any hepatic pathology virtually establishes the diagnosis of YST.[1],[8] Immunohistochemical (IHC) staining with AFP and AE1/AE3 are more sensitive to YST compared to other GCTs. Glypican-3 and CDX2 are newer highly sensitive markers for YST though they occasionally stain positively in other GCTs as well. Inclusion of other antigens such as CD117 or PLAP (+ in seminoma), CD30 (+ in embryonal carcinoma), and OCT3/4 (+ in seminoma and embryonal carcinoma) into the panel can be helpful in diagnosing a YST, particularly as the minor component of mixed-type EGCT.[9],[10] Accordingly, Khanchel-Lakhoua et al.[9] relied upon the IHC to diagnose a sacrococcygeal YST. However, in a review study on EGCTs, Hsu et al.[8] noticed that the serological evaluation of tumor markers, aided by simultaneous histopathological corroboration, carries the highest convenience among researchers. The primordial cytological characterization of the present tumor as germ cell derivatives actually simplified the subsequent diagnostic work-ups. Serum AFP and LDH were high, with an unaltered β-hCG and LFT. Ultimately, on histopathology, the tumor exhibited characteristic morphology of YST.
Overexpression of transcription factor GATA-4, hypermethylation of RUNX3 gene promoter, and missense mutation in high-mobility group box of the sex-determining region Y gene – these are the various molecular pathogenetic pathways projected in YST. However, respective application of microarray, bisulfite genomic sequencing, or western blotting, and fluorescent in situ hybridization (FISH) failed to validate these genetic abnormalities on recurrent basis.[11],[12] Rather, chromosomal aberrations such as loss of 1p and 6q, and gain of 1q and 20q are much consistent findings in YSTs. Polymerase chain reaction and FISH easily demonstrate these abnormalities.[12]
| Conclusion | | |
An internalized sacrococcygeal GCT should be suspected in a child, suffering from lung secondaries early in life. An advanced stage at its presentation is attributable to the minimally observable deformity. Thenceforth, despite being a tremendously chemo-sensitive malignancy, such sacrococcygeal YSTs often carry a grave prognosis.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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Correspondence Address:
Dr. Krishnendu Mondal
C/O-Barendra Nath Mondal, Vill-Fularhat, P.O. and P.S. Sonarpur, South 24 Parganas, Kolkata - 700 150, West Bengal
India
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/IJPM.IJPM_385_16
[Figure 1], [Figure 2] |
