Type I Pleuropulmonary Blastoma: Pathology and Biology Study of 51 Cases From the International Pleuropulmonary Blastoma Registry

Abstract

Pleuropulmonary blastoma (PPB) is a malignant neoplasm of the lung that presents in early childhood. The early form of the disease, cystic type I PPB, can be clinically and pathologically deceptive because of its resemblance to some developmental lung cysts. This study reviews 51 cases of type I PPB and 6 lung cysts from relatives of children with PPB. Type I PPB is a delicate multilocular cyst with variable numbers of primitive mesenchymal cells beneath a benign epithelial surface. Rhabdomyoblasts and cartilage nodules are seen in 49% and 40% of cases, respectively. Tumors in the youngest subset of patients, from birth to 2 months of age, are more uniform in composition and cellularity compared with those in older groups. Early tumors have a subtle transition between normal developing lung and tumor, showing bland interstitial mesenchymal cells uniformly expanding the alveolar septa. Presumed regressive changes including cyst wall necrosis are common. This phenomenon may explain the variable and sometimes sparse tumor cellularity seen in some type I PPBs. On a biologic level, this process supports the concept that not all type I PPBs are fated to progress to a type II or III PPB. Factors that control the balance between progression and regression may be important in predicting tumor behavior and determining which patients will benefit from adjuvant chemotherapy. In the meantime, recognition of this lesion as a neoplasm with malignant potential rather than a developmental cystic malformation is vital so the child can receive complete excision and appropriate follow-up care.

Pulmonary cysts in early childhood and the risk of malignancy

“…Our current view is that the cysts associated with PPB are not CPAM; PPB-associated cysts are separate diagnosable pathologic entities (Fig. 2B) described in detail elsewhere 47 and summarized below. In the context of PPB and early childhood lung cysts, CPAM type 4 requires additional discussion.…”

“…Recent observations suggest that, at the Type I PPB stage, the primitive cells may undergo partial or even complete regression. 47 It is not uncommon in children with multifocal PPB to have some cysts with the characteristic and diagnostic cambium layers of small primitive cells with or without rhabdomyoblastic differentiation and other histologically examined cysts showing the characteristic Type I PPB multilocular cystic architecture but no tumor cells. In addition, in 10 individuals, 8 of whom were family members of PPB patients, we have found lung cysts architecturally characteristic of Type I PPB but without any remnants of the primitive cells.…”

“…In a recent IPPBR report, 22 of 51 IPPBR Type I cases (43%) presented with pneumothorax. 47 Type I PPB may also be discovered incidentally by in utero ultrasound 6,58 or a later chest radiograph. Type I PPB is most often a multilocular cyst located in peripheral lung adjacent to or involving visceral pleura.…”

“…29,47 The telltale population of small primitive mesenchymal cells is found in the stroma beneath the benign epithelial lining; these cells may be a localized single focus, several foci or a diffuse proliferation resembling the cambium layer effect of a sarcoma botryoides. In fact, these primitive small cells may display } (Fig.…”

“…2B) may be found in the septa and are not necessarily accompanied by the small primitive cells. 29,47 Because the small primitive cells or nodules of cartilage are present only focally in some cases, it may be necessary to submit an entire cyst specimen for microscopic examination. We wish to emphasize that it is the low magnification appearance of a multicystic structure with delicate septa which should raise the possibility of cystic Type I PPB.…”