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The International Pleuropulmonary Blastoma Registry
The International Pleuropulmonary Blastoma Registry

PPB Basic Facts

Types I, II, III, and Ir PPB

PPB is subdivided into three pathologic subtypes, determined by laboratory examination of the surgical specimen. Type I PPB is purely cystic in appearance with no grossly identifiable nodular disease. Type III PPB is entirely solid disease with no grossly detectable cystic areas. There may be “cyst”-like spaces created by grossly necrotic/degenerated tumor which can be seen microscopically to be different from the “true” cysts of Type I (see Pathology of PPB). Type II PPB presents with both grossly apparent cystic and solid disease.

Type I can recur as Type I PPB, but it has also, in up to 10% of the cases, progress to Type II or III. Regression of Types II and III has not been observed. Type "progression" occurs along the same time spectrum as "de novo" PPB cases. That is, children diagnosed with Type I (median diagnosis age 10 months) who progress to Type II or III will do so at approximately ages 36-75 months. [see Registry Publications Priest 2006; Messinger abstract 2012 Type I and Type Ir.]


Type Ir (regressed) PPB

Since 2006 PPB Registry pathologists have recognized a fourth “Type” of PPB called “Type Ir PPB” for “Type I-regressed PPB”. This is a cystic lesion similar to Type I PPB. It has a micro-architecture similar to Type I with very delicate septawithoutmalignant cells. There may be small spindle cells which are not primitive and foci of dystrophic calcification. It appears to be a lesion which has “regressed’ from an earlier Type I or, alternatively, it is a genetically-determined lung cyst which did not evolve so far along a dysplastic path as to become malignant. Type Ir was initially recognized in several members of families in which one or more relatives had frank PPB. Subsequently, Type Ir has also been recognized in a few individuals with no known PPB relatives. Type Ir may present with pneumothorax. It may exhibit large or small lung cysts and may be an incidental finding in a relative of a PPB patient. Type Ir is recognized in individuals from infancy to adulthood. The cysts of Type Ir are different from other lung cyst pathologies included in “congenital pulmonary airway malformation” (CPAM) or congenital cystic adenomatoid malformation (CCAM) categories. Pathologists encountering unusual lung cysts are encouraged to obtain consultation from PPB Registry pathologists at no cost. [See Registry Publications Hill 2008; Messinger abstract 2012 Type I and Type Ir.]

Type Ir PPB Upfront chemotherapy and progression (ASCO 2012, Abstract No. 9522):

Progression

No Progression

Total

Type I:

Surgery + Chemotherapy

2

29

31*

Surgery only

6

25

31

Unknown

1

27

28

Type Ir:

Surgery + Chemotherapy

1

1

2**

Surgery only

1

19

20

Unknown

0

2

2

Excluding 2 chemotherapy treated patients: for 2nd malignancy*, and for concurrent rhabdomyosarcoma**

The PPB Spectrum: one disease from cyst to solid tumor over ~ 6 years

PPB is unique among pediatric cancers. It is manifested in the youngest patients as a multilocular cyst with only very subtle evidence of malignancy in cyst walls (Type I PPB: median diagnosis age 10 mo). Over the next 2-5 years, the malignant cells overgrow the cyst walls and septa to become an overt cystic and solid malignancy (Type II PPB: median diagnosis age 35 mo) and then a completely solid high-grade mixed-pattern sarcoma (Type III PPB: median diagnosis is age 41 months). [see Registry Publications Priest 2008.] The following is data supporting this biologic sequence.

Lung cysts precede development of PPB in many children. In 19 of 50 published Registry cases of PPB, air-filled cysts were present radiographically at diagnosis [see Registry Publications Priest 1997.] In 5 of these cases, pneumothorax had occurred. Cysts may be multiloculated or unilocular. They may be multifocal and unilateral or bilateral. Lung cysts were known to have been present for months in some patients. Lung cysts have been present in childhood in siblings, parents, and more distant relatives of PPB patients.

When children with lung cysts come to surgery, the cysts may be purely cystic Type I PPB. However, in numerous Registry and literature cases, Types II and III PPB have developed in children with known pre-existing lung cysts. In 28 such cases, cysts were discovered between birth and 48 months of age (median 18 months of age). Type II or III emerged 2 weeks to 96 months after a cyst was first noted (median 20.5 months later). The PPB diagnosis was made between ages 5 and 144 months (median 36 months of age at PPB diagnosis) [unpublished data]. In a most striking case, reviewed by the Registry, the lung cyst was observed for 8 years before emergence of Type II at age 12 years. PPB Registry pathologists have recognized a fourth “Type” of PPB, Type Ir PPB for “Type I-regressed PPB”. This is a cystic lesion similar to Type I but withoutmalignant cells. Type Ir is recognized in individuals from infancy to adulthood. It is now recognized that 2 of 25 children with Type Ir PPB have progressed to Type II/III, in one case after surgery and radiation. Thus finding a Type Ir PPB in a young child may not preclude progression. [see Registry Publications Messinger abstract 2012 Type I and Type Ir.]

To see a graphic display of the Cyst-to-PPB time course in 22 children, click here.


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Data and recommendations on this site are conscientiously presented but some are unpublished observations and have not undergone peer review. Consultation with the Registry is encouraged to clarify any topics. The International PPB Registry advises caution in the citation of website information.
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