PMID- 29794871
OWN - NLM
STAT- MEDLINE
DCOM- 20191115
LR  - 20191115
IS  - 1532-0979 (Electronic)
IS  - 0147-5185 (Linking)
VI  - 43
IP  - 1
DP  - 2019 Jan
TI  - ALK-rearranged Tumors Are Highly Enriched in the STUMP Subcategory of Uterine 
      Tumors.
PG  - 64-74
LID - 10.1097/PAS.0000000000001083 [doi]
AB  - Smooth muscle tumor of uncertain malignant potential (STUMP) is a rare diagnosis 
      rendered when there is uncertainty concerning the biological potential of a 
      smooth muscle tumor. The initial differential diagnosis is often broad, as tumors 
      in this subgroup are morphologically heterogenous. Recent data suggest uterine 
      inflammatory myofibroblastic tumors (IMTs) with anaplastic lymphoma kinase (ALK) 
      rearrangement may be misclassified as STUMPs, but the extent to which this occurs 
      has not been examined. We identified 60 female patients with tumors previously 
      diagnosed as STUMP (48 cases) or prospectively considered for the diagnosis of 
      STUMP (12 cases). Each case underwent histologic review, ALK immunohistochemistry 
      (IHC) and confirmatory break-apart fluorescence in situ hybridization (FISH) for 
      ALK if immunoreactive. Six of the 43 (14%) uterine and cervical tumors were ALK 
      IHC positive, whereas tumors at all other sites were ALK IHC negative. Myxoid 
      features, although limited in some cases, were present in all 6 ALK IHC positive 
      tumors, representing 35% (6/17) of tumors displaying myxoid features at uterine 
      and cervical sites. All ALK immunoreactive tumors were confirmed to have ALK 
      rearrangements by FISH with 1 tumor showing numerous (3 to 8) 3' ALK signals, an 
      unusual FISH pattern not previously described in uterine IMTs. Two patients 
      developed recurrent disease and were treated with ALK-targeted therapy with 
      initial response. Our data demonstrate that a significant proportion of uterine 
      and cervical tumors considered to be STUMPs are ALK-positive by IHC and FISH. 
      Future screening of all uterine and cervical mesenchymal tumors under 
      consideration for the diagnosis of STUMP, particularly those with myxoid 
      features, is recommended to identify ALK-rearranged IMTs that could potentially 
      be treated with targeted therapy using tyrosine kinase inhibitors.
FAU - Devereaux, Kelly A
AU  - Devereaux KA
AD  - Department of Pathology, Stanford University School of Medicine, Stanford, CA.
FAU - Kunder, Christian A
AU  - Kunder CA
FAU - Longacre, Teri A
AU  - Longacre TA
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Am J Surg Pathol
JT  - The American journal of surgical pathology
JID - 7707904
RN  - EC 2.7.10.1 (ALK protein, human)
RN  - EC 2.7.10.1 (Anaplastic Lymphoma Kinase)
SB  - IM
MH  - Adult
MH  - Anaplastic Lymphoma Kinase/analysis/*genetics
MH  - Diagnosis, Differential
MH  - Female
MH  - Gene Rearrangement
MH  - Humans
MH  - Middle Aged
MH  - Myofibroma/diagnosis/genetics
MH  - Smooth Muscle Tumor/*diagnosis/genetics
MH  - Uterine Neoplasms/*diagnosis/genetics
MH  - Young Adult
EDAT- 2018/05/26 06:00
MHDA- 2019/11/16 06:00
CRDT- 2018/05/26 06:00
PHST- 2018/05/26 06:00 [pubmed]
PHST- 2019/11/16 06:00 [medline]
PHST- 2018/05/26 06:00 [entrez]
AID - 10.1097/PAS.0000000000001083 [doi]
PST - ppublish
SO  - Am J Surg Pathol. 2019 Jan;43(1):64-74. doi: 10.1097/PAS.0000000000001083.