Upload
lekhuong
View
216
Download
0
Embed Size (px)
Citation preview
Invasive Stratified Mucin-producing Carcinoma (iSMILE) of the Cervix – A Study in
Morphology, Immunohistochemistry and Human Papillomavirus Status
Kay J. Park, MDMemorial Sloan Kettering Cancer CenterNew York (formerly New Amsterdam), NY
USA
Stratified Mucin-Producing Intraepithelial Lesions of the Cervix: Adenosquamous or Columnar Cell Neoplasia?
Park, Jeong-Ja; Sun, Deqin; Quade, Bradley; Flynn, Cythia; Sheets, Ellen; Yang, Annie; McKeon, Frank; Crum, Christopher AJSP 24(10):1414-1419, October 2000
•Immature intraepithelial lesion with stratified cells similar to CIN
•Conspicuous mucin or cytoplasmic clearing separating cells throughout
•Absence of classic gland formation (AIS)
• Mucicarmine highlights mucin throughout
•Resembles SIL when mucin poor
•Adenosquamous lesion or columnar cell variant?
Cytoplasmic clearing Discrete vacuoles
Stratified Mucin-Producing Intraepithelial Lesions of the Cervix: Adenosquamous or Columnar Cell Neoplasia?
Park, Jeong-Ja; Sun, Deqin; Quade, Bradley; Flynn, Cythia; Sheets, Ellen; Yang, Annie; McKeon, Frank; Crum, Christopher AJSP 24(10):1414-1419, October 2000
• Associated lesions with SMILE (n=18)– CIN2-3, AIS, adenocarcinoma, adenosquamous
carcinoma, squamous carcinoma
• 9/18 (50%) associated with invasive carcinoma– Adenocarcinoma (n=4)
– Adenosquamous carcinoma (n=5)
– SCC (n=1)
Marker of phenotypicinstability
• Coexistence with other findings:– 7 cases of SMILE
associated with invasive ca• 6 SCC, 1 Adeno
– AIS present in 42%– CIN present in 93%
• IHC– IMP3 negative (closer to
CIN than AIS immunophenotypically)
– p16 diffuse strong
“Reserve cell dysplasia” preferred, management like AIS
2015
Stratified mucin-producing intraepithelial lesion of the cervix: A diagnostic challengeJoerg Schwock,, Marjan Rouzbahman, William R. Geddie.CytoJournal. 2014;11:22.
Diagnostic Cytopathology, Vol. 42, No 9
Follow-up of patients with SMILE
(stratified mucin producing intraepithelial
lesion) on the cervix--a dilemma. Gupta S, Parsons P, Saha A, Wight C.
Eur J Obstet Gynecol Reprod Biol. 2010 Feb;148(2):207-9.
Diagnostic Cytopathology, Vol. 44, No 1
Invasive SMILE (iSMILE) defined as:Invasive growth with nests or cords of stratified columnar cells that contain intracytoplasmic mucin
Human Pathology (2016) 55, 174–181
9 invasive carcinomas associated with SMILE•5 Adenocarcinoma (E) (3 iSMILE, 2 Usu, 1 Villog)•2 Adenosquamous carcinoma•1 Adenoca and separate SCC•1 Large cell neuroendocrine carcinoma (F)
iSMILE
• Cell of origin?
• Glandular, Squamous or Both?
• Associated tumors?
• Morphologic variation?
OBJECTIVE• To determine the frequency of iSMILE in a cohort
of adenoca and adenosquamous ca• To describe the morphologic variation of iSMILE
and any other associated histotypes• To determine the immunohistochemical profile of
iSMILE• To determine HPV status and interrogate specific
HPV subtypes (16, 18, 45)
METHODS• Part of a larger study of endocervical adenocarcinomas
– All cases called adenocarcinoma or adenosquamous carcinoma were reviewed
• Categorized by histologic subtype– Adenocarcinoma– Adenosquamous carcinoma– Glassy cell carcinoma– Adenocarcinoma with squamous metaplasia– iSMILE (used definition of Lastra et al.)
METHODS
• Morphology of iSMILE and other associated histologic subtypes:– Usual endocervical adenocarcinoma
– Mucinous adenocarcinoma
– Adenosquamous carcinoma
– Pure
– Any other variations
METHODS• Tissue microarray (TMA) constructed• Immunohistochemistry and HPV detection performed
RNAscope® E6/E7 mRNA
Detects transcriptionally active HPV 16,18,26,31,33,35,39,45,51,52,53,56,58,59,66,68,73,82
Type specific HPV 16, 18 and 45 also performed
RESULTS: iSMILE• Total Adenocarcinomas/Adenosquamous: 409Total iSMILE: 21 (5%)
9 PURE12 ASSOCIATED WITH OTHER SUBTYPES
• 6 USUAL• 3 ADENOSQUAMOUS• 3 MUCINOUS• Other histologic features also noted
POSITIVE NEGATIVE
P16 (8/12) 67% HIK1083
PAX8 (2/7) 29% SATB2
P40 (2/7) 29% CDX2
P63 (1/11) 9% AR
PR (3/12) 25% *p53 (2/11) 18%
CA-IX (4/7) 57%
MUC6 (4/7) 57%
HNF1beta (5/12) 42%
GATA 3 (1/7) 14%
Vimentin (1/12) 8%
Her2 (1/12 - 2+) 8%
RESULTS: IHC
*2 p53 “null” but on TMA
DISCUSSION
iSMILE is characterized by• Mucin/clear vacuoles throughout thickness
• Nested
• Peripheral palisading
• Neutrophilic infiltrate
• Apoptotic bodies and mitoses
DISCUSSION• Question of adenocarcinoma vs adenosquamous
– P40 and p63 often positive, patchy pattern, typically in peripheral cells
– PAX8 less frequently positive
• The frequent expression of p63/p40 and lack of PAX8 in iSMILE suggests that it is likely of reserve cell origin
• TMA study has limitations
DISCUSSION• The presence of mucin suggests it is differentiating
toward glandular epithelium• The frequent association with other subtypes suggests
a phenotypic fluidity – Usual endocervical adenocarcinoma– Squamous diff (keratin or intercellular bridges)– Glassy cell-like– Signet ring-like– Micropapillary– Clear cytoplasm
CONCLUSIONInvasive Stratified Mucin-producing Carcinoma
HPV associated (16, 18)
Morphologically distinct but with…
Phenotypic fluidity – can be pure or mixed and often thought to be adenosquamous carcinoma
Likely of reserve cell origin and retains pluripotential ability True Adenosquamous???