part 2 - legeforeningen · part 2 slides 39-71, rita alaggio soft tissue tumors trondheim 14. mars...
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Part 2
Slides 39-71, Rita Alaggio
Soft tissue tumors
Trondheim 14. mars 2013
RHABDOMYOSARCOMA
Histologic Classification (WHO 2002)
Embryonal RMS Botryoid Classic Anaplastic
Spindle cell /Scleosing RMS Alveolar RMS Classic
Solid
ALVEOLAR RMS
“Alveolar rhabdomyosarcoma is a primitive, malignant, round cell neoplasm that cytologically resembles lymphoma and which shows partial skeletal muscle differentiation.”
WHO 2002
“A highly cellular malignant neoplasm containing a monomorphous population of primitive cells with round nuclei and features of arrested myogenesis.”
WHO 2013
ALVEOLAR RMS
“Alveolar rhabdomyosarcoma is a primitive, malignant, round cell neoplasm that cytologically resembles lymphoma and which shows partial skeletal muscle differentiation.”
WHO 2002
“A highly cellular malignant neoplasm containing a monomorphous population of primitive cells with round nuclei and features of arrested myogenesis. Most cases exhibit PAX3-FOXO1 or PAX7-FOXO1 fusion gene”
WHO 2013
Round monomorphic cells with high N/C ratio. Fibrovascular septae in a picket-fence pattern, wreath-like cells
Round monomorphic cells with high N/C ratio.
ARMS TRANSLOCATION NEGATIVE?
• ARMS carrying other translocations (NCOA family genes)
• ARMS “Low-expressors” of the transcripts
ARMS translocation negative?
WHO 2013 HAS PARTIALLY PROVIDED TO THE “RE-CLASSIFICATION” OF SOME ARMS TRANSLOCATION NEGATIVE
-
CASE 1: MIXED ARMS, t-
A-MIXED ARMS
Mixed embryonal / alveolar RMS contain foci with embryonal histology, i.e., myxoid stroma and spindle cell myoblasts as well as areas with alveolar histology.
WHO 2002
“…but most of these lack PAX-FOXO1 fusions thus appearing to be clinically and biologically more akin to ERMS. However, fusion genes have been detected in rare cases of mixed ERMS-ARMS ”
WHO 2013
CASE 2
Post-therapy lung metastasis, same case
B-RMS WITH ANAPLASIA
“The presence of enlarged, atypical cells with hyperchromatic nuclei defines the anaplastic variant of rhabdomyosarcoma.
This feature may be seen in both embryonal and alveolar tumours but is more prevalent in the former. Bizarre, multipolar mitoses are also often present. Anaplastic features can be focal or diffuse.
Focal anaplasia indicates the presence of only single, dispersed anaplastic cells, whereas diffuse anaplasia indicates the presence of clone-like clusters of anaplastic cells.”
WHO 2002
“The presence of enlarged, atypical cells with hyperchromatic nuclei defines the anaplastic variant of rhabdomyosarcoma.”
WHO 2013
CASE 3
RMS A PRACTICAL APPROACH TO THE DIAGNOSIS
Immunohistochemistry
Desmin
Immunohistochemistry
P Pax 7 MyoD, Myogenin Desmin
ERMS+ ERMS++
ERMS+++ ARMS+++
RH
30
10-2
10-3
10-4
10-1
10-6
10-5
H2O
U9
37
MW
PAX3-FKHR
ARMS RT-PCR
Translocation Gene fusion % Clinical features
t(2;13) (q35;q14) PAX3-FKHR 55 Older age
Higher tumor invasiveness
Increased risk of marrow metastases
Worse survival in Stage IV patients
t(1;13)(p36;q14) PAX7-FKHR 22 Younger age
Improved survival in Stage IV patients
AP2 beta and p-cadherin in ARMS t+
EGFR and Fibrillin 2 in ERMS
New markers identified by molecular profiling
EGFR
ERMS
AP2 beta
ERMS ARMS
BULLIT-POINTS
• In the current WHO classification Spindle cell RMS are distinct from ERMS and include the sclerosing-subtype
• ARMS translocation negative behave like ERMS and in the next future will be treated as ERMS
• The ERMS category will be probably re-visited in the future …