Squamoid Cyst of Pancreatic Ducts: A Distinct Type of Cystic Lesion in the Pancreas Squamoid Cyst of Pancreatic Ducts: A Distinct Type of Cystic Lesion

Squamoid Cyst of Pancreatic DucSquamoid Cyst of Pancreatic Ducts: A Distinct Type of Cystic Lesiots: A Distinct Type of Cystic Lesio

n in the Pancreasn in the PancreasMohammad Othman, MD,* Olca Basturk, MD,* Gabe Groism

an, MD,wAlyssa Krasinskas, MD,z and N. Volkan Adsay, MD*

From the *Department of Pathology, Wayne State University and Karmanos

Cancer Institute, Detroit, MI; Department of Pathology, Hillel-Yaffe Medical

Center, Hadera, Israel; and Department of Pathology, University of Pittsburgh,

Pittsburgh, PA Supported in part by National Cancer Institute Specialized

Program in Research Excellence (SPORE) CA101936. Reprints: N. Volkan

Adsay, MD, Harper Hospital and Wayne State University, 3990 John R. Street,

Detroit, MI 48021 (e-mail:[email protected])

報告人： Intern 劉洋帆

IntroductionIntroduction

Solid tumor of pancrease:Solid tumor of pancrease:

ductal adenocarcinoma ductal adenocarcinoma dismal prognosis dismal prognosis

Most cystic lesion: Most cystic lesion:

benign or low-grade malignancybenign or low-grade malignancy

More amenable to curative resectionMore amenable to curative resection

IntroductionIntroductionCystic tumors are detected increasingly more Cystic tumors are detected increasingly more common in resection specimenscommon in resection specimensMore and more ‘‘incidental’’ pancreatic cysts to More and more ‘‘incidental’’ pancreatic cysts to the attention of surgical pathologiststhe attention of surgical pathologistsSix case of squamoid cyst of pancreatic ducts Six case of squamoid cyst of pancreatic ducts (a distinct type of cystic lesion)(a distinct type of cystic lesion)Represent a cystic dilatation of ductsRepresent a cystic dilatation of ductsPresumably originating from intercalated ductsPresumably originating from intercalated ductsMetaplastic squamous/transitional transformatiMetaplastic squamous/transitional transformationon

Review ArticleReview Article

Seminars in Diagnostic PathologySeminars in Diagnostic PathologyVOL 17, NO 1VOL 17, NO 1February 2000February 2000Cystic pancreatic neoplasmsCystic pancreatic neoplasmsDuctal adenocarcinomas: Ductal adenocarcinomas:

the majority of pancreatic neoplasmthe majority of pancreatic neoplasmCystic lesion: Cystic lesion:

non-neoplastic(ex:pseudocyst), neoplasticnon-neoplastic(ex:pseudocyst), neoplastic

Mechanistic division of cystic neoplMechanistic division of cystic neoplasms: 3 general categoriesasms: 3 general categories

Inherently cystic tumors: form epithelial-linInherently cystic tumors: form epithelial-linked cystic spacesked cystic spaces

The cystic change is of a degenerative natThe cystic change is of a degenerative natureure

Intraductal pancreatic tumors (associate wiIntraductal pancreatic tumors (associate with marked cystic dilatation of the ductal syth marked cystic dilatation of the ductal system)stem)

Cystic pancreatic tumorCystic pancreatic tumor

Preoperative evaluation of the Preoperative evaluation of the cystic pancreatic lesioncystic pancreatic lesion

Surgical resection may not be necessary in somSurgical resection may not be necessary in some instance:e instance:

(1) Asymptomatic serous cystic tumors in (1) Asymptomatic serous cystic tumors in older patientsolder patients (2) Pseudocysts (2) Pseudocysts medical treatment or surgical medical treatment or surgical drainagedrainage

Radiographic studies: CT, Ultrasound, ERCPRadiographic studies: CT, Ultrasound, ERCPAspiration cytologyAspiration cytologyCystic fluid analysisCystic fluid analysis

Distingishing Clinical FeaturesDistingishing Clinical Features

History (pancreatitis, alcoholism History (pancreatitis, alcoholism pseudocyst) pseudocyst)AgeAgeSex (many cystic tumors are more common in womeSex (many cystic tumors are more common in women)n)Location ~~Location ~~

Head: IPMNs (intraductal papillary mucinous Head: IPMNs (intraductal papillary mucinous neoplasm)neoplasm) Tail: mucinous cystic tumors are almost Tail: mucinous cystic tumors are almost exclusiveexclusive to the tailto the tail

Sex Ratios for Cystic Tumors of the Sex Ratios for Cystic Tumors of the PancreasPancreas

Approximate age ranges of cystic Approximate age ranges of cystic tumors of the pancreastumors of the pancreas

SPT: Solid Pseudopapillary TumorMCN: Mucinous Cystic Neoplasm

SCA: Serous CystadenomaLEC: Lymphoepithelial Cysts

IPMN: Intraductal Papillary Mucinous Neoplasm

6 cases of Squamoid Cyst of Pancr6 cases of Squamoid Cyst of Pancreatic Ducts (SCOPs)eatic Ducts (SCOPs)

TwoTwo: in the consultation files of one of the au: in the consultation files of one of the authors (N.V.A.)thors (N.V.A.)OneOne: in the institutional files of Wayne State : in the institutional files of Wayne State University and Karmanos CancerInstitute, DeUniversity and Karmanos CancerInstitute, Detroit, MI(which contains 92 cystic lesions)troit, MI(which contains 92 cystic lesions)TwoTwo: in the files of University of Pittsburgh, Pi: in the files of University of Pittsburgh, Pittsburg, PAttsburg, PAOneOne: in Hillel-Yaffe Medical Center, Hadera, I: in Hillel-Yaffe Medical Center, Hadera, Israelsrael

Section of other 110 pancreatic Section of other 110 pancreatic resection (Incidental Examples)resection (Incidental Examples)

Wayne State University and Karmanos Cancer InstiWayne State University and Karmanos Cancer Institutetute96 adenocarcinomas, 8 endocrine tumors, 6 cystic l96 adenocarcinomas, 8 endocrine tumors, 6 cystic lesionsesionsIn average, 5.3 slides of normal pancreas per case In average, 5.3 slides of normal pancreas per case were examinedwere examinedTen casesTen cases showed the presence of these microsco showed the presence of these microscopic cystspic cystsThe location, the age, and the sex of the patients, aThe location, the age, and the sex of the patients, associated clinical features, and indications for surgessociated clinical features, and indications for surgery were recorded.ry were recorded.

ImmunohistocemistryImmunohistocemistry

Nuclear Nuclear p63p63 expression: a marker of squa expression: a marker of squamous/transitional epitheliummous/transitional epithelium


MUC 1MUC 1 and and MUC 6MUC 6: intercalated duct centr: intercalated duct centroacinar cell markeroacinar cell marker

GLUT-1GLUT-1: a glycogen clear cell marker posit: a glycogen clear cell marker positive in most serous tumorsive in most serous tumors

InhibinInhibin: a marker for serous neoplasms: a marker for serous neoplasms

Ki67Ki67: Ki67 Ab recognize a nuclear protein i: Ki67 Ab recognize a nuclear protein involved in proliferative portion of cell cyclenvolved in proliferative portion of cell cycle


CK7CK7: Nongastrointestinally derived carcino: Nongastrointestinally derived carcinomasmas

CK19CK19: Most carcinomas, many carcinoma: Most carcinomas, many carcinomas with squamous component; myoepithelias with squamous component; myoepithelial cellsl cells

CK20CK20: Most gastrointestinal carcinomas; : Most gastrointestinal carcinomas; mucinous ovarian, biliary, transitional, and mucinous ovarian, biliary, transitional, and Merkel cell carcinomaMerkel cell carcinoma

Clinic pathologic Features of Case 1 Clinic pathologic Features of Case 1

77 y/o, woman 77 y/o, woman

10-year history of pancreatic cyst10-year history of pancreatic cyst

Increasing size of cyst (9 cm) on follow upIncreasing size of cyst (9 cm) on follow up

Exploratory laparotomyExploratory laparotomy

Quite adherent to pancreatic headQuite adherent to pancreatic head

Wipple operation Wipple operation

Clinicopathologic Features of Case 2Clinicopathologic Features of Case 2

76 y/o, man76 y/o, manAbdominopelvic CTAbdominopelvic CTHigh prostate-specific AgHigh prostate-specific Ag0.9 cm cyst in the body of pancrease0.9 cm cyst in the body of pancreaseCEA, CA19-9 --> normalCEA, CA19-9 --> normalChemical analysis of fluid Chemical analysis of fluid eleated CEA eleated CEA & CA19-9& CA19-9Subtotal pancreatectomySubtotal pancreatectomy


52 y/o, woman52 y/o, womanNauseaNauseaRUQ abdominal pain radiating to the back RUQ abdominal pain radiating to the back without fever chills, or vomitingwithout fever chills, or vomitingRadiogram Radiogram 2 cm cystic lesion in pancrea 2 cm cystic lesion in pancreatic headtic headNodule within the cystNodule within the cystInterpreted Interpreted mucinous cyst neoplasm mucinous cyst neoplasmWhipple procedureWhipple procedure


9 y/o, woman9 y/o, woman

Multiple episodes of backacheMultiple episodes of backache

CT scan CT scan 2 cm cyst in pancreatic tail 2 cm cyst in pancreatic tail

Serum tumor marker (-)Serum tumor marker (-)

Distal pancreatectomyDistal pancreatectomy


59 y/o, man59 y/o, man

CT scan CT scan pancreatic mass pancreatic mass

CEA in the cyst fluid was elevatedCEA in the cyst fluid was elevated

Whipple procedureWhipple procedure


66 y/o, man 66 y/o, man

CT scan CT scan pancreatic mass pancreatic mass

Whipple procedureWhipple procedure

Clinicopathologic Data of 6 Cases of SClinicopathologic Data of 6 Cases of Squamoid Cyst of Pancreatic Ductquamoid Cyst of Pancreatic Duct

Mean age: 63 y/o(52~79 y/o)

3 men , 3 women

Mean size: 2.6 cm(0.8 ~ 9 cm)

Macroscopic findingMacroscopic findingUnilocularUnilocularWell demarcated with a relatively thin fibroWell demarcated with a relatively thin fibrotic wall ( < 1 mm in most areas)tic wall ( < 1 mm in most areas)Smooth, shiny inner surfaces that were deSmooth, shiny inner surfaces that were devoid of solid areas or papillary excrescencvoid of solid areas or papillary excrescences es ((贅生物贅生物 ;;瘤瘤 ))

Contain serous clear fluid with aggregates Contain serous clear fluid with aggregates of minute, concretionlike, ‘‘flaky off-white of minute, concretionlike, ‘‘flaky off-white ((黃白色的黃白色的 ;;灰白色的灰白色的 ))’’ material’’ materialNo fibrosis of pancreatic parenchymaNo fibrosis of pancreatic parenchymaNo dilatation of main pancreatic ductNo dilatation of main pancreatic duct

Macroscopic findingMacroscopic finding

Macroscopic findingMacroscopic finding

Microscopic findingMicroscopic finding

Variable liningVariable lining

Ranging from attenuated, flat squamoid cells Ranging from attenuated, flat squamoid cells to transitional, to stratified squamous without to transitional, to stratified squamous without keratinizationkeratinization


Squamoid cyst of pancreatic duct with various typesof lining including squamoid, transitional (A and B)


some cases also attenuated (lower aspect of C)

Microscopic findingMicroscopic findingNo tall columnar mucinous or acinar cell were No tall columnar mucinous or acinar cell were identifiedidentified

Degenerated cell with abundent granular palDegenerated cell with abundent granular pale-foamy cytoplasm (balloon cells) e-foamy cytoplasm (balloon cells) in case 4 in case 4

No associated lymphoid or splenic tissueNo associated lymphoid or splenic tissue

The cyst walls were composed of relatively thiThe cyst walls were composed of relatively thin, paucicellular fibrous tissuen, paucicellular fibrous tissue

None of these cystic lesions displayed ovariaNone of these cystic lesions displayed ovarianlike stromanlike stroma


No significant evidence of pancreatitis (atrNo significant evidence of pancreatitis (atrophy, fibrosis, or inflammation) in the immophy, fibrosis, or inflammation) in the immediately adjacent parenchymaediately adjacent parenchyma

No fat necrosisNo fat necrosis

In 4 cases, mucoproteinaceous dense eosiIn 4 cases, mucoproteinaceous dense eosinophilic material characteristic of enzymatinophilic material characteristic of enzymatic concretions could be identified in the cysc concretions could be identified in the cyst luminat lumina


Immunohistochemical FindingsImmunohistochemical Findings



Findings in Patients With Microscopic/Findings in Patients With Microscopic/Incidental LesionsIncidental Lesions

10 of the 110 pancreatectomy specimens rev10 of the 110 pancreatectomy specimens reviewediewed

6 men, 4 women6 men, 4 women

Age range was 56 to 85 years (mean 63 y)Age range was 56 to 85 years (mean 63 y)

All 10 of these microscopic examples were idAll 10 of these microscopic examples were identified in pancreata resected for adenocarcientified in pancreata resected for adenocarcinoma.noma.


Acute and chronic pancreatitis Acute and chronic pancreatitis one case one case

Peritumoral chronic pancreatitis Peritumoral chronic pancreatitis one case one case

In the remainder of cases, the adjacent pancIn the remainder of cases, the adjacent pancreas was devoid of any significant pathologyreas was devoid of any significant pathology

The cysts were located mainly in the pancreThe cysts were located mainly in the pancreatic headatic head

The largest example was 4mmThe largest example was 4mm


The cysts were very similar morphologically The cysts were very similar morphologically to the clinically manifested examples discusto the clinically manifested examples discussed abovesed above

These microcysts were mostly compact and These microcysts were mostly compact and had abortive(nonbridging) septaehad abortive(nonbridging) septae

Pseudo-loculated and serrated appearance Pseudo-loculated and serrated appearance

Focally attenuated lining and abundant mucFocally attenuated lining and abundant mucoproteinaceous acinar secretionsoproteinaceous acinar secretions

Microscopic/incidental version of Squamoid cyst of pancreatic duct with abortive septa and pseudo-loculatedappearance (A and B)

The cyst lumen is filled with abundant mucoproteinaceous acinar secretions (C and D)

DISCUSSIONDISCUSSIONSquamoid cyst of pancreatic ducts (SCOP) seems tSquamoid cyst of pancreatic ducts (SCOP) seems to be the most appropriate descriptive term, may pro be the most appropriate descriptive term, may present as a cystic mass in the pancreas.esent as a cystic mass in the pancreas.These are relatively small cysts with a median size These are relatively small cysts with a median size of 1.5 cmof 1.5 cmAdvents in imaging technology Advents in imaging technology recently coming t recently coming to clinical attentiono clinical attention4/6 of our cases were diagnosed during work-up for 4/6 of our cases were diagnosed during work-up for other conditions other conditions Only 2 had symptoms attributable to the cystOnly 2 had symptoms attributable to the cystit is not surprising that these cysts are detected at ait is not surprising that these cysts are detected at an older agen older age

DISCUSSIONDISCUSSION

SCOP has morphologic & immunophenotypic cSCOP has morphologic & immunophenotypic characteristics that distinguish it from other cystiharacteristics that distinguish it from other cystic lesions in this organc lesions in this organ

Neither acute nor chronic inflammation is a feaNeither acute nor chronic inflammation is a feature of this lesionture of this lesion

The cysts contain serous fluid with material deThe cysts contain serous fluid with material described macroscopically as flaky off-white or ‘‘iscribed macroscopically as flaky off-white or ‘‘impacted’’mpacted’’

DISCUSSIONDISCUSSIONNuclear p63 expression is present in all cases, a finding that is not seen in any normal component of pancreas or in nonsquamous cystic lesions of this organ

MUC 1 and MUC 6 are expressed in larger lesions but not as much in what appear to be microscopic examples of this entity

GLUT-1, which is consistently present in serous cystic tumors, is either absent or focal

CK 7, CK 19 positivity and lacking CK 20

Differential Diagnosis from mucinouDifferential Diagnosis from mucinous tumors tumor

Mucinous cystic neoplasms (having ovariaMucinous cystic neoplasms (having ovarian-like stroma)n-like stroma)

Intraductal papillary mucinous neoplasms Intraductal papillary mucinous neoplasms (can D/D by ERCP)(can D/D by ERCP)

Pancreatic intraepithelial neoplasiaPancreatic intraepithelial neoplasia

Prenvasive v.s innocuousPrenvasive v.s innocuous

Differential Diagnosis from mucinouDifferential Diagnosis from mucinous tumors tumor

In well-preserved sections, the microscopic In well-preserved sections, the microscopic differential diagnosis of SCOPs from mucindifferential diagnosis of SCOPs from mucinous tumors can be accomplished fairly ous tumors can be accomplished fairly easileasily by the lack of mucinous cellsy by the lack of mucinous cellsIn attenuated or nonsquamous areas, the cIn attenuated or nonsquamous areas, the cells may superficially resemble those of higells may superficially resemble those of high-grade intraductal neoplasiah-grade intraductal neoplasiaAbsence of papillae, tufting, apoptosis, and Absence of papillae, tufting, apoptosis, and mitotic activitymitotic activity are helpful are helpful

Differential Diagnosis from squamoDifferential Diagnosis from squamous-lined cysts of pancreasus-lined cysts of pancreas

Lymphoepithelial cystsLymphoepithelial cysts

Epidermoid cyst of intrapancreatic accessEpidermoid cyst of intrapancreatic accessory spleenory spleen

SCOPs lack underlining lymphoid band or SCOPs lack underlining lymphoid band or splenic-type tissuesplenic-type tissue


Most lymphoepithelial cysts are peripancreatiMost lymphoepithelial cysts are peripancreatic and seem to be intranodal, whereas c and seem to be intranodal, whereas SCOPSCOPs are intraductal, and predominantly surrounds are intraductal, and predominantly surrounded by pancreatic tissueed by pancreatic tissue

Lymphoepithelial cysts occur predominantly iLymphoepithelial cysts occur predominantly in men (M/F=4/1), whereas n men (M/F=4/1), whereas SCOPs do not apSCOPs do not appear to have sex predominancepear to have sex predominance


Ortho or parakeratosis are typically seen iOrtho or parakeratosis are typically seen in lymphoepithelial cysts, often (but not alwn lymphoepithelial cysts, often (but not always) with prominent granular layer and abuays) with prominent granular layer and abundant keratin material in the lumen that imndant keratin material in the lumen that imparts a grumous appearance to the cyst coparts a grumous appearance to the cyst contents, which is not a feature of SCOPsntents, which is not a feature of SCOPsSCOPs do not show adnexal-type elementSCOPs do not show adnexal-type elementss (sebaceous glands, hair, etc.) that are se (sebaceous glands, hair, etc.) that are seen in dermoid cystsen in dermoid cysts

Differential Diagnosis from Differential Diagnosis from serous oligocystic adenomasserous oligocystic adenomas

Serous oligocystic adenomas often have aSerous oligocystic adenomas often have attenuated lining, resembling the larger SCttenuated lining, resembling the larger SCOPs with more attenuated liningOPs with more attenuated lining

Serous oligocystic adenoma is otherwise cSerous oligocystic adenoma is otherwise characterized by a single-layer of clear cells haracterized by a single-layer of clear cells with distinct cytoplasmic borders and small,with distinct cytoplasmic borders and small, round nuclei with dense chromatin round nuclei with dense chromatin

Differential Diagnosis from Differential Diagnosis from serous oligocystic adenomasserous oligocystic adenomas

Both express MUC 1 and MUC 6Both express MUC 1 and MUC 6, suggesti, suggesting a kinship to centroacinar/intercalated dng a kinship to centroacinar/intercalated duct systemuct system

GLUT-1GLUT-1, a marker consistently present in , a marker consistently present in serous tumors serous tumors is rarely (and only focally) pis rarely (and only focally) positive in SCOPsositive in SCOPs

Possible Origin and EtiopathogenesisPossible Origin and Etiopathogenesis

SCOP represents a cystic dilatation of the natSCOP represents a cystic dilatation of the native ductsive ducts, rather than a de-novo cyst formatio, rather than a de-novo cyst formation; that is, it is an intraductal processn; that is, it is an intraductal processThe immunophenotype confirms the The immunophenotype confirms the squamousquamous/transitional nature of the epithelial linings/transitional nature of the epithelial lining ( (p6p633 nuclear expression, which is not otherwise nuclear expression, which is not otherwise detected in any other components of the pancdetected in any other components of the pancreas) reas) Relationship to the Relationship to the centroacinar/intercalated dcentroacinar/intercalated duct systemuct system (with (with MUC 1MUC 1 and and MUC 6MUC 6 expressi expression)on)


The presence of The presence of acinar secretionsacinar secretions confirm confirms that they communicate with the acinar sys that they communicate with the acinar systemstem

Surrounded by compact acinar tissue, and Surrounded by compact acinar tissue, and both by location and distribution seem to rboth by location and distribution seem to represent epresent cystic dilatationcystic dilatation of the of the centroacincentroacinar cell/intercalated duct unitar cell/intercalated duct unit


In the case of SCOP, the epithelial cells chooIn the case of SCOP, the epithelial cells choose the path of squamous transformationse the path of squamous transformationIt can be speculated that formation of squamIt can be speculated that formation of squamous/transitional type epithelium may reflect aous/transitional type epithelium may reflect an n inability to form mucinous cellsinability to form mucinous cellsPresumed ‘‘suppressor’’ activity of p63Presumed ‘‘suppressor’’ activity of p63, a kin, a kindred of p53, dred of p53, may have a role in the diversion may have a role in the diversion of the proliferating cells towardsof the proliferating cells towards squamous rather than mucinous lineage


Ki-67 labeling in SCOPsKi-67 labeling in SCOPs indicate that the indicate that the pproliferative activity in these lesions is fairly roliferative activity in these lesions is fairly lowlow

SummarySummarySCOP is a hitherto uncharacterized distinct type of cSCOP is a hitherto uncharacterized distinct type of cystic lesion in the pancreasystic lesion in the pancreas

It is important to distinguish SCOPs from other cystic It is important to distinguish SCOPs from other cystic lesions, in particular, lesions, in particular, from mucinous tumorsfrom mucinous tumors (often h (often has malignant potential)as malignant potential)

Preoperative differential diagnosis of these may be vPreoperative differential diagnosis of these may be very difficultery difficult

Tumor markers (CEA and CA19-9) may be high in STumor markers (CEA and CA19-9) may be high in SCOPs COPs

Distinction at the microscopic level is fairly easyDistinction at the microscopic level is fairly easy

SummarySummary

More and more asymptomatic cystic lesionMore and more asymptomatic cystic lesions are detected radiologicallys are detected radiologically

More cases of SCOPs will come to the attMore cases of SCOPs will come to the attention of surgical pathologistsention of surgical pathologists

It is important to recognize and distinguish It is important to recognize and distinguish this benign lesion from other cystic neoplathis benign lesion from other cystic neoplasia of this organsia of this organ

Thanks for your attention!!Thanks for your attention!!

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Squamoid Cyst of Pancreatic Ducts: A Distinct Type of Cystic Lesion in the Pancreas Squamoid Cyst of Pancreatic Ducts: A Distinct Type of Cystic Lesion