Relationship of Type I PPB to Types II and III: The PPB/DICER1 Registry believes that Type I, Type II, and Type III PPB are on a biologic continuum. The median ages at diagnosis of Types I, II, and III are, respectively, 10, 34, and 44 months. First, most Type I PPB cases which recur do so as Type II or III disease. Second, numerous Registry and literature cases reveal that Type II and III PPB develop in children known to have pre-existing, unoperated lung cysts. The cysts have been discovered incidentally or following pneumothorax. The cysts have typically been discovered by 30 months of age. Type II or III PPB emerged between 24 and 60 months of age, although one Registry-reviewed case was observed in the cyst stage for 8 years before emergence of Type II PPB [Search PubMed or Google Scholar for these literature articles: Hasioutou M. et al. Pleuropulmonary blastoma in the area of a previously diagnosed congenital lung cyst: report of two cases. Acta Radiologica 2004;3:289-92; Dosios T et al. Pleuropulmonary blastoma in childhood. A malignant degeneration of pulmonary cysts. Pediatr Surg Int 2004;20:863-5 (same cases)]. Based on the ultimate development of PPB in these children, we believe that the cysts observed earlier may have been undiagnosed Type I PPB. Type I PPB is the early cystic form of the disease and is not a benign cyst which undergoes “degeneration”. [Registry Publications Dehner 2005].
Type II PPB
Pathology Diagnosis: Type II PPB is a cystic and solid neoplasm. Like Type I PPB, a cystic pattern is identified grossly or, in an otherwise predominantly solid neoplasm, microscopically by remnants of septa. The cystic regions in Type II have the same characteristics as in Type I; the cysts are lined with ciliated columnar respiratory epithelium and may have a sub-epithelial condensation of tumor cells with a sarcoma botryoid-like appearance. When the specimen is predominantly cystic, Type II PPB is differentiated from Type I PPB by thickened or plaque-like areas composed of an overgrowth of rhabdomyosarcomatous, spindle cell sarcomatous, or blastematous elements. Even within septae that are not obviously thickened or nodular at gross examination, this complex microscopic appearance is sufficient to categorize a tumor as Type II PPB. It remains to be determined whether there is a prognostic difference between microscopic and macroscopic Type II PPB because there is clearly a distinction in the solid tumor burden.
The microscopic characteristics of the manifestly solid portions of Type II PPB are described below in the section on Type III PPB.
The site of origin of Type II PPB may be difficult to determine. Lesions may be clearly pleural (visceral or parietal) or may be clearly intraparenchymal. It is common for them to nearly fill the hemithorax. It is unusual for thoracic lymph nodes to be involved.
Type III PPB
Pathology Diagnosis: Type III PPB tumors are homogeneous or heterogeneous solid masses with or without involvement of chest wall or mediastinal structures. The entire hemithorax may be opacified by the mass. Grossly, a well-circumscribed, solid, mucoid, tan-white and friable mass with pleural attachments involving a lobe or entire lung is seen. Hemorrhage and necrosis account in part for the friability of the tumor. If the tumor has extended into the surrounding pleural space, the resection specimen may be submitted in a piecemeal fashion.
The site of origin of Types II and III PPB may be difficult to determine. They may be clearly pleural (visceral or parietal) or may be clearly intraparenchymal. It is common for them to nearly fill the hemithorax. It is unusual for thoracic lymph nodes to be involved.
The solid areas of tumor in Type II and III PPB have mixed blastematous and sarcomatous features. One of the prominent patterns is comprised of cellular islands of small, primitive, blastematous cells with oval nuclei, granular chromatin, and inconspicuous nucleoli; these cells have little discernible cytoplasm and mitotic figures are numerous. The stroma in the blastematous foci often blends into spindle cell sarcomatous areas with a vague fascicular pattern of malignant fibrous histiocytoma or fibrosarcoma. Or the stroma may be sharply demarcated from the blastematous islands and have a less densely cellular appearance of short, oval-to-fusiform cells in a pale-staining background and have a resemblance to the stroma surrounding the blastema of a Wilms’ tumor.
Foci of skeletal muscle differentiation including polygonal or elongated rhabdomyoblasts, often with cross-striations, either as isolated cells or as groups of cells are found in most cases. This is similar to the rhabdomyoblastic differentiation found in Type I. If such cells are not obvious by routine histology, they are often found by immunohistochemistry. Cartilaginous differentiation, either in the form of chondroid matrix or well-formed islands of hyaline cartilage, is found in most, but not all, cases of Type II and Type III. Although the chondroid component is usually a minor one, it is occasionally prominent enough to suggest the possibility of chondrosarcoma. The nodules of cartilage, when present, have a degree of cellularity and atypia to qualify as chondrosarcoma in most cases. In other cases, the cartilage has immature or fetal features.
Focal cellular anaplasia in the form of giant, bizarre-appearing pleomorphic cells with irregular hyperchromatic nuclei is present in most, but not all, cases of Type II and Type III. Anaplastic cells are not found in the blastematous or chondroid foci, but rather in the uncommitted mesenchymal foci or, less often, in the rhabdomyoblastic areas. As noted above, anaplasia is not seen in Type I.
Necrosis, occasionally producing apparent “cystic” change, is a prominent feature in the solid areas and is consistent with the common surgical finding of highly friable, necrotic or empyematous tissue. These “cystic” areas do not show the epithelial lining that defines the “true” cysts of Type I and Type II. Less frequently observed are areas of myxoid degeneration producing myxoid pools or areas with a pericytomatous or liposarcomatous pattern; these findings also should not be interpreted as “true” cysts.
(Please see photomicrographs below)
Individual or groupings of large anaplastic cells with highly atypical mitotic figures are present in many Type II and most Type III cases. Eosinophilic hyaline bodies are often seen in association with anaplastic cells. The Registry is studying the prognostic significance of anaplasia, as judged by Wilms’ tumor criteria and other histologic features of PPB [Registry Publications Serrano abstract 2005]. Within any one tumor, not all patterns are equally represented and one or two patterns may dominate the overall microscopic appearance.
In Type II and Type III PPB, differentiation from a benign process is not an issue. Depending on the predominance of one or more sarcomatous or blastemal elements, the differential diagnosis includes primary and metastatic rhabdomyosarcoma, malignant teratoma, synovial sarcoma and other spindle cell or undifferentiated sarcomas. In solid tumors with a predominant blastemal pattern, metastatic Wilms tumor could be considered and a good radiographic study or cytokeratin immunohistochemistry (PPB is negative for cytokeratin) would be helpful in making this latter distinction.
The following is a list of Registry diagnoses on cases submitted as PPB in which the Registry pathologists did not believe they could confirm PPB:
- bi-phasic tumors
- adult-type biphasic pulmonary blastoma
- carcinosarcoma with lymph node metastasis
- non-PPB sarcomas
- monophasic synovial sarcoma (primary pleuropulmonary synovial sarcoma)
- congenital infantile fibrosarcoma
- embryonal rhabdomyosarcoma
- high grade sarcoma, NOS
- immature interstitial mesenchymal neoplasm
- undifferentiated sarcoma with myxochondrosarcomatous features
- myxoid chondrosarcoma (metastatic from thigh)
- scalp lesion mets:pulmonary leiomyosarcoma
- spindle cell sarcoma
- undifferentiated sarcoma
- Germ cell tumors
- immature teratoma
- undifferentiated embryonic (probably ovarian)chest neoplasm (probably a metastasis of prior ovarian teratoma)
- endodermal sinus (yolk-sac) tumor
- fetal lung interstitial tumor (immature interstitial mesenchymal tumor)
- miscellaneous diagnoses
- malignant epithelial neoplasm
- Askin tumor - chest wall PNET
- malignant rhabdoid tumor (with intracadiac extension)
- malignant neoplasm (prob. inflammatory myofibroblastic tumor with malignant transformation)
- anaplastic large cell lymphoma, null cell type
- malignant solitary fibrous tumor
In some cases, needle core biopsies have been used to make a PPB diagnosis; upon Registry review, Registry pathologists believe the biopsies may indeed suggest, but not be conclusively diagnostic of, PPB. Small biopsies do not always contain the heterogeneity of histologic appearances that is so characteristic of PPB.
Examples of Type II-III PPB Pathology Findings: (This is the Type III PPB lesion in the chest CT slice shown above)
Type II & III PPB: Four histologic patterns in Type II and III PPB: