| Abstract|| |
Pleuropulmonary blastoma (PPB) is a rare variably aggressive, dysodontogenetic, childhood primary intrathoracic malignancy which in up to 25% of cases can be extrapulmonary with attachment to the parietal pleura. It is found in pediatric population under 5 years of age. It was initially proposed as a distinct entity by Manivel et al. in 1988. PPB is a proliferation of primitive mesenchymal cells that initially form air-filled cysts lined by benign-appearing epithelium (type I, cystic). Later on, the mesenchymal cells outgrow the cysts with formation of focal solid areas (type II, solid and cystic) and finally, mainly solid mass (type III, solid PPB). Here we intend to document a rare case of PPB type III in a 2-year male presenting with an extensive tumor occupying the right hemithorax with immunohistochemical (IHC) study.
Keywords: Lung tumors, pediatric malignancy, PPB
|How to cite this URL:|
Sinai Khandeparkar SG, Kulkarni MM, Gogate BP, Dhavan CS. A rare case of Pleuropulmonary blastoma type III with Immunohistochemical Study. Indian J Pathol Microbiol [Epub ahead of print] [cited 2023 Feb 2]. Available from: https://www.ijpmonline.org/preprintarticle.asp?id=367706
| Introduction|| |
Pleuropulmonary blastoma (PPB) is a rare variably aggressive, dysodontogenetic, childhood primary intrathoracic malignancy which in up to 25% of cases can be extrapulmonary with attachment to the parietal pleura. It is found in pediatric population under 5 years of age. It was initially proposed as a distinct entity by Manivel et al. in 1988. Its primitive, sarcomatous features are analogous to those of other dysembryonic tumors such as Wilm's tumor, hepatoblastoma, neuroblastoma, and embryonal rhabdomyosarcoma. PPB is a proliferation of primitive mesenchymal cells that initially form air-filled cysts lined by benign-appearing epithelium (type I, cystic). Later on, the mesenchymal cells outgrow the cysts with formation of focal solid areas (type II, solid and cystic) and finally, mainly solid mass (type III, solid PPB).
Here we intend to document a rare case of PPB type III in a 2-year male presenting with an extensive tumor occupying the right hemithorax with immunohistochemical (IHC) study.
| Case Report|| |
A 2-year male presented to surgery outpatient department with history of fever, cough and cold for 8 days. A swelling was noted over the right side of the chest for 3 days. There was rapid breathing for 2 days. Other systemic examination findings were noncontributory. Computed tomography (CT) of the chest showed a well defined heterogeneously enhancing soft tissue density lesion occupying the entire right hemithorax. [Figure 1]a. Multiple non-enhancing areas were noted within the lesion suggestive of necrosis. Few areas of calcification were seen. The lesion measured 13 × 9.2 × 8.2 cm. It was causing compression collapse of the entire right lung. There was shift of mediastinal structures towards left. The lesion was abutting the intercostal spaces of the right hemithorax posteriorly. No obvious connection with the neural foramina of the thoracic vertebra was visible. No evidence of rib and vertebral erosion was seen. Fat planes between the lesion and right hemidiaphragm was preserved. No evidence of extra-thoracic extension was seen. Mild right pleural effusion was noted. No mediastinal lymphadenopathy was noted. The radiologist suggested a neoplastic lesion such as pulmonary neuroblastoma. Pleural fluid study revealed reddish, turbid fluid containing 25--30/high power field red blood cells, 1,750/mm3 total nucleated cells of which were 85% neutrophils and 15% lymphocytes. Cytospin smears studied did not show presence of neoplastic cells.
|Figure 1: (a) Computed tomography showing well defined heterogeneously enhancing soft tissue density lesion occupying the entire right hemithorax with compression collapse of the entire right lung with shift of mediastinal structures towards left, (b) Gross photograph of middle and lower lobe of lung showing relatively well circumscribed greyish white nodules of tumor measuring 10 × 8 × 2.5 cm|
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Right pneumonectomy (middle and lower lobe) was performed and the specimen was submitted for histopathological examination. Intraoperatively, good expansion of the normal upper lobe of the right lung was observed. The entire specimen received measured 13 × 10 × 2.5 cm. Cut surface showed multiple relatively well circumscribed, grayish white tumor nodules. The entire area of these nodular masses measured 10 × 8 × 2.5 cm in the middle and lower lobe of the lung. [Figure 1]b Pleura (visceral) was seen adhered to the lung and opaque. All the surgical margins of resection of the lung appeared free grossly. Microscopic examination of the sections taken from the tumor [Figure 2] showed a relatively circumscribed tumor mass composed of heterogenous areas of blastema like elements having small cells with hyperchromatic nuclei, high nucleocytoplasmic ratio and scant cytoplasm blending into spindled to ovoid cells with vesicular and pleomorphic nucleus embedded in myxoid stroma (sarcomatous areas). Areas of mature and immature chondroid elements were seen. Few rosettes and anaplastic cells showing hyperchromatic nucleus exhibiting pleomorphism and multinucleation were noted in the blastemal areas. Such anaplastic cells were noted in the sarcomatous areas too. Rhabdomyoblast like cells with eccentric nucleus and moderate amount of eosinophilic cytoplasm were seen. Numerous brisk abnormal unipolar and multipolar mitotic figures were noted in blastemal and sarcomatous areas. Sections from the surrounding lung showed edema and congestion.
|Figure 2: (a) Photomicrograph showing blastemal and sarcomatous areas with a inset) rhabdomyoblasts (Hematoxylin and Eosin, ×100), (b) Photomicrograph showing anaplastic cells in sarcomatous areas (Hematoxylin and Eosin, ×100), (c) Photomicrograph showing anaplastic features in blastemal areas, (d) Photomicrograph showing edema in alveoli in surrounding lung tissue, (e) tumor cells showing strong cytoplasmic immunoreactivity for vimentin in blastemal areas (×400) and (f) rhabdomyoblasts showing desmin reactivity|
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Histopathological diagnosis of pleuropulmonary blastoma type III was given. Representative sections were subjected for immunohistochemical studies (IHC). The tumour cells showed focal immunoreactivity for vimentin in blastemal areas. Rhabdomyoblasts were positive for desmin. S100 highlighted the cartilaginous areas. Epithelial membrane antigen (EMA) was non-immunoreactive. This reinforced the diagnosis of pleuropulmonary blastoma type III.
The patient was discharged on postoperative day 10. The child was referred to an oncology centre for further management. Positron emission tomography CT done showed no mediastinal disease. The patient received intensive multidrug chemotherapy [vincristine (V), adriamycin (A), cyclophosphamide (C), ifosfamide (I) and etoposide (E)] as per the EFT 2001 protocol. The patient received alternate two cycles of VAC and VIE three weeklies for total 8 courses. After which patient underwent chest X-ray, complete blood count and biochemical investigations which were unremarkable. He is disease free over a period of 3 years.
| Discussion|| |
The median ages at diagnosis of PPB type I, II and III are 8, 35 and 41 months, respectively. The chief signs and symptoms at diagnosis include respiratory distress, fever, chest/abdominal pain, cough, anorexia and malaise. Pneumonia is the initial clinical impression in most cases. Our patient was a 2-year male and presented with fever, cough and rapid breathing.
Radiologically PPB I presents as pulmonary cysts which are evidenced as pneumothorax. Enlarging cysts or mass can also be seen over time. Intraoperatively, PPB III is seen as extensive tumor involving the hemithorax and lower lobe is more commonly affected as compared to middle or upper lobe. Pleural effusion is documented in some cases. Often these tumors are incompletely resectable and it is difficult to tell the accurate site of origin (lung or visceral pleura) once the anatomic relations are lost. Indications for surgery include presence of pulmonary cysts, pneumothorax, presumed infectious/inflammatory process such as empyema, infected cysts or unresolved pneumonia and intra thoracic mass lesion. In this case, radiology showed soft tissue density lesion occupying the entire right hemithorax. Pleural effusion was noted in this case.
Grossly these tumors range from 2 to 28 cm. PPB I are mainly cystic with thin-walled structures. Type IV congenital cystic adenomatoid malformation needs generous sampling to rule out PPB type I. PPB II are cystic and solid which show nodules or plaque like thickenings or solid polypoid projections into the cystic areas. PPB III show well to ill circumscribed, white tan solid mass attached to the pleura and involves the lobe or an entire lung with mucoid foci, friable areas of necrosis and hemorrhage. In this case multiple nodular greyish white masses were seen. Microscopically, PPB I are multiloculated cysts lined by ciliated pseudostratified columnar epithelium beneath which is seen cambium layer like presence of primitive tumor cells which are accompanied by rhabdomyoblast like cells which need careful sectioning and evaluation. Solid areas in PPB II and III show blastematous and sarcomatous elements which either are seen as distinctive foci or blend in each other. Rhabdomyoblast like cells are often noticed. Cartilaginous areas are also seen which either could have an appearance of immature form or sarcoma like. Anaplastic cells are also noted in the uncommitted mesenchymal foci. Necrosis and myxoid areas are often seen. Most of the features of PPB III were noted in this case.
IHC study shows blastematous elements being weakly positive for vimentin which also stains the cartilaginous and fibrosarcoma like areas. Blastema area stains weakly for neuron specific enolase. S100 stains the cartilaginous areas. Cytokeratin staining is limited to the epithelium lining the cysts. Smooth muscle actin and desmin positivity is seen in rhabdomyoblasts.
Radiological and pathological differential diagnoses to be ruled out in present case were neuroblastoma (lack of small round blue cells, homer wright rosettes), rhabdomyosarcoma with cartilaginous metaplasia (lack of diffuse strong vimentin, smooth muscle actin and desmin immunoreactivity in tumor cells), immature teratoma (presence of characteristic clinicopathological findings of PPB, absence of extensive multilineage differentiation) and metastatic Wilm's and germ cell tumor (absence of primary determined by meticulous clinico-radiological investigations).
Pulmonary blastoma of adults should not be confused with PPB. Unlike PPB, pulmonary blastoma is a sarcomatoid carcinoma of adults, along with pleomorphic carcinoma, spindle cell carcinoma, giant cell carcinoma and carcinosarcoma. The sarcomatous component of these tumors is thought to derive from carcinoma cells during the progression of carcinogenesis through the activation of an epithelial-mesenchymal transition program which stains variably with low and high molecular weight cytokeratin, EMA and carcinoembryonic antigen (CEA) and vimentin, respectively.
Recurrence of the tumor and metastasis chiefly to the brain/spinal cord, bone, liver and soft tissue is observed in mainly PPB II and III cases. A subtype of type I PPB has been recently described by the International Pleuropulmonary Blastoma Registry as type I regressed PPB (type Ir PPB) implying regression or non-progression. These are cystic tumors containing few spindle shaped cells in the cyst wall with few foci of dystrophic calcification but without subepithelial malignant cell condensation. Only 8% of such tumors show onward progression to PPB type II or type III.
Approximately 20% of PPBs are part of an inherited cancer syndrome where there is family history of cystic nephroma of the kidney or rhabdomyosarcoma. A family-based linkage study mapped the PPB locus to 14q and identified DICER1 as potentially the gene responsible for mutations leading to PPB. DICER1 IHC of PPB tumors suggest that expression of the wild-type allele is lost in tumor-associated epithelium, but is retained in the mesenchymal cells. This absence of staining in the tumoral epithelium was segmental in most cases. The genetic basis behind this altered expression in epithelium is currently unknown. No relevant family history was noted and DICER1 IHC study was not done in this case.
Surgical excision with adjuvant chemotherapy forms the mainstay of therapy in PPB I cases. For type Ir PPB only follow-up is recommended. For the type III PPB aggressive surgery and chemotherapy is given. Radiation therapy is reserved for patients with known but non-resectable tumors or for residual tumors after chemotherapy.,,, Overall survival at 2 years is 63% for all patients (80% for type I, 73% for type II and 48% for type III). The overall survival for 5 years is 45%. Patients with mediastinal or pleural involvement have significantly poorer survival than those having parenchymal involvement only. Middle and lower right lung lobes were resected in this case with clear surgical cut margins and patient received extensive chemotherapy with multidrug agents as per the EFT 2001 protocol. He did not receive radiotherapy. He is disease free for a period of 3 years.
Our experience with the present case highlights the rarity of the lesion and need for documentation of such rare case in Indian scenario, importance of clinico-radiological and immuno-histopathological correlation along with high index of suspicion for arriving at an accurate diagnosis of pulmonary masses in pediatric patients.
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.
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Conflicts of interest
There are no conflicts of interest.
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Siddhi Gaurish Sinai Khandeparkar,
E-517, The Island, Wakad, Pune - 411 057, Maharashtra
Source of Support: None, Conflict of Interest: None
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