Annals of Diagnostic Paediatric Pathology

78
Fig. 9 In ganglioneuroblastoma,
nodular, a ganglioneuromatous
component surrounds nodule(s) of
neuroblastic stroma-poor tumor
tissue (a). Note lack of protein S-
100-positive Schwannian stroma
innside the nodule (b).
Fig. 10 The neuroblastic nodule (left) shows pushing borders by compressing
the surrounding ganglioneuromatous tissue (right).
Table 1 shows the prognostic allocation of the morphological
categories and subtypes of pNTs as recommended in the INPC.
The process of reaching a final histoprognostic conclusion
according to differentiation, MKI and age may appear confusing
to the inexperienced. For newcomers, it can be recommended
to learn the favorable categories by heart because their
number is quite low: poorly differentiated and differentiating
tumors with low and intermediate MKI below 1,5 years, and
differentiating neuroblastoma with low MKI between 1,5 and
5 years. All other neuroblastomas are actually unfavorable.
Similar to the Shimada classification of 1984, Schwannian
stroma-rich and dominant tumors have a favorable prognosis
unrelated to the patient’s age, except for nodular
ganglioneuroblastomas which all are ascribed an unfavorable
outcome.
Revision of the International Neuroblastoma Pathology
Classification (INPC)
Both Joshi [12] and the International Neuroblastoma Pathology
Committee [24, 25] mentioned the possibility of performing
a prognostic grading of nodular ganglioneuroblastoma
(GNBn) on the basis of the stroma-poor nodule(s) since this
component of the tumor had been regarded as the malignant
one already many years ago [28]. However, the number of
GNBns in their reviews was too small.
Umehara et al. [29] were the first to review 70 GNBns
and to perform a prognostic categorization by analyzing the
nodule(s) according to the above detailed criteria of the INPC
for neuroblastomatous tumors (morphology and MKI) and
relating their data to the patients’ age. These authors also described
GNBns with single or multiple nodules and variant
forms which (1) consisted mainly of the stroma-poor component
surrounded only by a thin, microscopically visible rim
of stroma-rich/-dominant tissue, and (2) only showed
ganglioneuromatous tissue in the primary tumor (probably due
to poor sampling), but a neuroblastomatous component at the
metastatic site. Depending on the presence of nodule(s) of the
favorable or unfavorable category, favorable (32,4%) and unfavorable
(67,7%) subsets of GNBn were established which
showed statistically significant differences in event free survival
and survival, quite similar to neuroblastic tumors.
In 2003, The International Neuroblastoma Pathology Committee
reviewed the same cohort of tumors and confirmed these
results [20]. A revision of the INPC was proposed including
the following terms: GNBn, classic, containing one nodule;
and variant forms containing either multiple nodules, large
nodules or no nodule, but a metastatic stroma-poor tumor.
Unfavorable prognosis was defined by the demonstration of
at least one nodule displaying features of the unfavorable INPC
categories of neuroblastomatous tumors.
The acceptance of a large nodule as a variant of GNBn
touches on one of the principles of the former INPC, which
claimed that a tumor belonging to the stroma-rich or -dominant
category has to be made up by >50% Schwannian stroma
(see above). It is important for pathologists to be aware of all
variants of GNBn because they were two times more frequent
than the classic form among the cases reviewed by Umehara
and Peuchmaur.
The greatest advantage of this INPC revision, however,
is brought by the recognition of a subset (about 30%)
of nodular ganglioneuroblastomas which, in contrast to previous
thinking, belong to a prognostic favorable category
which might benefit from a milder therapeutic regime.