Type I

To collect a large group of Types I, II and III PPB patients for event-free and overall survival analysis, the PPB/DICER1 Registry is enrolling participants on the new Treatment and Biology Registry protocol

PPB/DICER1 Registry Treatment Recommendations

PPB therapy choices are the decision of each institution. The Treatment and Biology Registry presents surgery and chemotherapy guidelines. Through the Treatment and Biology Registry protocol study it is anticipated that analysis of a group of similarly treated children with PPB will advance the knowledge of effective ways to treat PPB.

The secured PPB Registry Treatment and Biology Registry Information Portal provides physicians further details for treating Types I, II, and III PPB, including a copy of the Registry’s treatment protocol and consent forms.

The International PPB/DICER1 Registry is not a part of, nor funded by, any cooperative oncology group, although Children’s Oncology Group Rare Tumor Sub-Committee recognizes the Registry as a major collection of PPB cases.

The PPB/DICER1 Registry offers the following treatment recommendations for Type I PPB based on anecdotal Registry and literature information discussed below.

Surgery - Type I PPB

In many Type I cases, the indication for surgery is cystic lung disease and there is little pre-operative concern about a malignancy. The clues to a malignant process would be bilateral cystic lung disease*, an extensive multilocular cyst*, or any family history of lung cysts, cystic nephroma, or childhood cancer. See Constitutional Disease: Lung Cysts and More and Familial Disease and Dysplastic and Neoplastic Conditions in PPB Patients and their Families. (*Bilaterality rarely occurs also in benign cystic lung malformations.)

This study recommends thoracotomy for predominantly cystic lesions. However, because pre-operative evaluation of predominantly cystic lesions is unlikely to suggest malignancy, thorascopic resections may be undertaken.

Type I disease is entirely cystic and may be unilocular or multilocular, unifocal or multifocal, and unilateral or bilateral. Every attempt should be made to remove completely all cystic remnants, but the Registry has seen cases in which not all cysts in a Type I patient show the changes of Type I PPB. Therefore, the Registry understands that in children with widespread cystic lung changes, not all the cysts can or should be removed. Type I recurrences frequently progress to more serious Type II or III disease (see Prognosis for PPB).

Chemotherapy - Type I PPB

For Types I PPB, the Registry recommends therapy using vincristine, actinomycin D, cyclophosphamide (VAC).

The PPB/DICER1 Registry published a series on Type I PPB (see Registry Publications: Priest et al 2006) which discusses 38 Type I PPB cases and includes literature and Registry cases. In this analysis, there is a suggestion that adjuvant chemotherapy improves outcome in Type I PPB.

As of Feb. 2011, the following is PPB Registry data on 80 Registry-reviewed Type I PPB cases (no literature cases):

International PPB/DICER1 Registry Type I PPB (n = 80)
(This data is published only in part; citation noted above)


Surgery without Adjuvant Chemotherapy

Surgery plus Adjuvant Chemotherapy

Total Cases

n = 47

n = 33

No Recurrence

n = 37

n = 32


n = 10*


n = 1**


* 8 of 10 recurrences were Type II or III PPB (time to recurrence from initial diagnosis: 3, 6, 12, 23, 30, 37, 39 and 47 months); 2 of 10 recurrences were Type I PPB (time to recurrence 3 and 7 months).

** Type III at recurrence, 54 months after diagnosis.

Most of the patients included in this collection were treated (1) before PPB was a well-known neoplastic entity and (2) before the natural history of PPB was well recognized, particularly the tendency of Type I disease to progress to Types II or III disease. Therefore, most patients did not have a “cancer operation” and were not followed closely for recurrence.

Worldwide, there is not a consensus on whether children with Type I PPB should receive adjuvant chemotherapy. When deciding whether to use chemotherapy for Type I PPB, clinicians treating children with Type I PPB should combine information in the 2006 Priest et al. Type I paper (see Registry Publications) with the Registry-only updated data reported here. In general, the PPB Registry recommends VAC-type chemotherapy for Type I PPB. Alternatively, aggressive follow-up of complete resection surgery-only Type I PPB patients might allow recurrences to be identified while still Type I disease, compelling additional surgery and chemotherapy at that time. A recurrence of Type I PPB as Type II or III disease markedly reduces the prognosis for the child. The Registry recommends chemotherapy for three reasons:

  • The tendency for Type I PPB to progressed at recurrence to Type II or III, which are poorly salvaged
  • The Wilms tumor experience with no chemotherapy for Stage I disease, which resulted in a 13% recurrence rate (with better salvage rates than appear to apply to PPB)
  • The general tolerability of VAC therapy

Regardless of whether the child receives chemotherapy for Type I, the Registry recommends diligent surveillance of Type I patients until they reach 60 months of age, because the risk of cysts becoming PPB recurrences cluster in the 3rd and 4th years of life. (See Recommendations: Surveillance.)

The secured PPB Registry Treatment and Biology Registry Information Portal provides physicians further details for treating Types I, II, and III PPB, including a copy of the Registry’s treatment protocol and consent forms.

Alternative to Adjuvant Chemotherapy for Type I PPB

Please also see Registry Publications: Priest et al 2006.
Perhaps an alternative to adjuvant chemotherapy in the child with completely resected Type I PPB is monitoring for early detection of recurrence. In three recent Registry cases, physicians have used a close surveillance strategy to modulate therapy for Type I PPB. The ultimate outcome in these children is not yet known. Examples are as follows: In one child, seven months after Type I PPB diagnosis, remaining cysts enlarged, were resected and showed Type I PPB; chemotherapy was then initiated. In another child, 16 months after Type I diagnosis, remaining cysts enlarged so they were surgically resected. Diagnostic features of Type I PPB were not seen in the residual cyst material, and the child continues to be observed without adjuvant chemotherapy. In a third child, 48 weeks of adjuvant chemotherapy was planned following Type I diagnosis. At 28 weeks, enlarging cysts were resected. Compared to the initial specimen, cyst walls showed hyalinized nodules, hemorrhage, abundant macrophages, and rare cartilage nodules with few nodules of primitive cells, consistent with chemotherapy effect. No residual confluent layers of primitive cells (cambium layer) were seen. Based on these findings, the original plan was continued.

A close surveillance schedule for Type I PPB recurrence must recognize that

  1. The natural history of PPB is cystic Type I PPB in the youngest patients, typically under age 2 years, with progression to solid disease in older children: Type II PPB average age of diagnosis 34 months and Type III PPB average age at diagnosis 44 months. Thus, Type I disease may recur as Type II or III PPB up to the age of about 60 months and rarely later (maximum age observed of a child with cystic lung disease which progressed to PPB was 12 years at progression; maximum age of a child with Type I PPB which recurred was 76 months at recurrence [54 months after PPB Type I diagnosis]),
  2. PPB recurrence may be fulminate and scans must be at 3-month intervals, and
  3. CT is the best surveillance modality.