|
|
Types I, II, and III PPB
PPB is subdivided into three pathologic subtypes, determined by laboratory examination of the surgical specimen. Type I is purely cystic in appearance with no grossly identifiable nodular disease. Type III 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 below). Type II presents grossly apparent cystic and solid disease.
If there is a recurrence of Type I PPB, it typically progresses to Type II or III PPB, or Type II progresses to Type III. Regression of Types II and III PPB has not been observed. Type "progression" occurs along the same time spectrum as "de novo" PPB cases. That is, children diagnosed with Type I PPB (median diagnosis age 9 months) who progress to Type II or III PPB will do so at approximately ages 36-60 months. (see Registry Publications Priest 2006)
Type Ir PPB
Since about 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 PPB with very delicate septa without malignant 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 PPB 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 PPB was initially recognized in several members of families in which one or more relatives had frank PPB. Subsequently, Type Ir PPB has also been recognized in a few individuals with no known PPB relatives. Type Ir PPB 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 PPB is recognized in individuals from childhood to adulthood. The cysts of Type Ir PPB 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)
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 9 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 33 mo) and then a completely solid high-grade mixed-pattern sarcoma (Type III PPB, median diagnosis age)(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 (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 PPB 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 PPB at age 12 years [Bibliography Dosios et al and Hasiotou et al (same cases)].
To see a graphic display of the Cyst-to-PPB Time Course in 22 children, click here.
|
|
