Challenging Case 1

Clinical history:
A 32-year-old male with a history of Hodgkin’s lymphoma and biliary atresia. He had undergone transplant and was found to have distal pancreas mass during surveillance.

Pathologic Findings:

Distal pancreatectomy revealed a 4.3 cm, well circumscribed, predominantly solid mass abutting the splenic vein.

Please see two representative scanned H&E slides for histologic features.

Performed immunohistochemical stains reveal that the tumor cells:

– Express: CAM 5.2 (scanned), CK19, CK5, Ber-EP4, claudin-4 (focal), calretinin (scanned), SATB2 (patchy), CD99 (patchy, membranous), inhibin (rare cells), CD10 (focal) and a Ki67 stain reveals a
proliferative rate of 15%.

– Do NOT express: CK7, CK20, CDX2, trypsin, chymotrypsin, carboxyl ester lipase, chromogranin, synaptophysin, INSM1, insulin, glucagon, somatostatin, pancreatic polypeptide, p40, p63, monoclonal CEA, EMA, TTF1, HepPar-1, Glypican-3, GATA3, PAX8, NKX3.1, SF-1, WT1, D2-40, SALL4, CD117, DOG1, CD34, SMA, calponin, ERG, CD45, S100, SOX10, melanoma cocktail

– Other: aberrant beta-catenin (nuclear and cytoplasmic, (scanned), E-cadherin (membranous), p53 wild-type, RB1 retained, ATRX retained, MMR retained, mucicarmine negative,

No mutations, deletions or fusions were seen by NGS.

HE-1

https://pathpresenter.net/public/display?token=f8789272

HE-2

https://pathpresenter.net/public/display?token=ca3927d4

Cam 5.2 IHC

https://pathpresenter.net/public/display?token=6e1b407d

Calretinin IHC

https://pathpresenter.net/public/display?token=b4d3bde0

Beta-catenin IHC

https://pathpresenter.net/public/display?token=cb61d7fb

NOTE: The case will be open for 2 weeks for discussion. Please leave a reply of your proposed diagnosis, differential diagnosis and suggested ancillary tests (bottom of this page). We will collect the replies and post the final diagnosis with discussion.

The PBPS is seeking a new Journal Watch Committee Member

The PBPS journal watch (JW) is seeking a new committee member to join our team for a term of 3 years. The JW is posted every 2 months and includes articles to be highlighted from the most relevant journals in pancreatobiliary pathology. The JW is a valued educational tool among our community and a great way to network with others in the field.  

Interested PBPS members should send CV to info@pbpath.org by June 8, 2022.  Applicants must be paid members of the Pancreatobiliary Pathology Society. 

Daniela Allende, MD MBA, PBPS JW Editor 

USCAP 2022 Companion Society Program

Pancreatobiliary Pathology Society Companion Meeting USCAP 2022

Clonal Evolution of Pancreatobiliary Neoplasms

Despite advances in the field, our understanding of the clonal evolution of neuroendocrine neoplasms and macroscopic precursor lesions of the pancreatobiliary tract remains incomplete. Until recently the genetic alterations that contribute to these tumors’ development, progression and resistance to treatment were poorly understood. New and specific genetic alterations have now been identified in precursor lesions and specific cancer phenotypes have been shown to be associated with targetable genomic events. These advances offer pathologists a better understanding of the underlying pathogenesis of these diseases and allow more precise diagnosis and classification. This session will focus on recent advances in our understanding of mechanisms and clinical implications of the clonal evolution of neuroendocrine neoplasms and macroscopic precursors of the pancreatobiliary tract.  Updates in grading and classification and the use of novel diagnostic/prognostic markers for characterization will also be included. These are essential to practicing pathologists and pathology trainees, as they play an increasing and critical role as consultants on test selection and integrated diagnostic interpretation. Dr. Aldo Scarpa will describe molecular tumorigenesis of pancreatic neuroendocrine neoplasia and its implications on diagnosis, disease progression, treatment and prognosis. Dr. Elizabeth Thompson will provide an overview of the genomics of pancreatic cancer development from its macroscopic precursors, including intraductal neoplasms and mucinous cystic neoplasms, along with their impact on our understanding of pancreas cancer biology, diagnosis, and treatment. Dr. Yoh Zen, who has worked on defining and classifying macroscopic precursor biliary tract lesions (tumoral intraepithelial neoplasia), and their molecular associations, will summarize the current state in this rapidly evolving area.

Learning Objectives: Upon completion of this educational activity, learners will be able to:

  1. Describe the underlying molecular alterations in neuroendocrine neoplasms, and their involvement in diagnosis, association with tumor progression, newly updated WHO grading and tumor progression as well as prognosis.
  2. Describe the spectrum of molecular alterations involved in the development and progression of macroscopic precursor lesions of the pancreas (including intraductal neoplasms and mucinous cystic neoplasms) and their importance in diagnostic workup and therapeutic implications.
  3. Understand the classification system for macroscopic precursor lesions of the biliary tree, the genomic basis for invasive carcinoma development and prognostic implications of these molecular alterations.

Continuing Medical Education

The United States and Canadian Academy of Pathology is accredited by the ACCME to provide continuing medical education for physicians.

The United States and Canadian Academy of Pathology designates this live activity for a maximum of 2.0 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.


Session Chairs

Moderator(s)
Daniela Allende, MD, Cleveland Clinic, Lerner College of Medicine of Case Western University School of Medicine
United States

David Klimstra, MD, Memorial Sloan Kettering Cancer Center
United States

 

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Abstract Award in USCAP 2022

Pancreatobiliary Pathology Society Abstract Award

Dear members of the PBPS,

The PBPS is now accepting applications for this year’s PBPS Abstract Award. This award will go to a pathology trainee with an abstract (poster/platform) in pancreatobiliary pathology presented at the 2022 annual USCAP meeting. Submitted abstracts will be evaluated for originality, scientific merit and presentation, and the winner will receive a $500 prize. At least one author should be a PBPS member. Trainees are strongly encouraged to apply.

The deadline for submission of Award applications is February 15, 2022.

Please email your completed abstract in Word format along with the information below to the education committee chair Dr. Michelle Reid (michelle.reid@emory.edu).

Name:
Training Institution:
Position:
PGY Year:
Date/Time of Presentation:
Abstract Name:
Poster Number (if applicable):

Case 5: Quarter 4, 2021

Case 5: Quarter 4, 2021

Clinical History

A 63-year-old male with past medical history that includes hyperparathyroidism presented with ongoing left hip pain. Evaluation of the etiology of his pain revealed an incidental mid-abdominal mass on lumbar spine MRI. A dedicated CT scan confirmed the presence of a solid, well-demarcated ovoid peripancreatic mass measuring 11 cm. A CT-guided needle biopsy was performed.

Macroscopic Description
N/A

Histologic/Cytologic Features 

Microscopic pictures of the biopsy are shown in Figures 1-3. The histologic examination revealed numerous dilated and thin-walled angulated vascular channels distributed in myxoid matrix. Nested around these vessels are clustered epithelioid to spindle- shaped cells with pale, amphophilic cytoplasm and somewhat atypical, vesicular nuclei. Mitotic figures are scarce and there is no necrosis or significant pleomorphism. Immunohistochemical (IHC) analysis was performed on the biopsy. The neoplastic cells were entirely negative for pan-keratin, CAM 5.2, S100, HMB45, Melan-A, SOX10, MDM2, CDK4, ERG, CD34, CD31, SMA, desmin and MITF.

Figure 1. Biopsy, low to moderate power, H&E.
Figure 2. Biopsy, low to moderate power, H&E.
Figure 3. Biopsy, high power, H&E.

Please select your diagnosis in the poll, then see the answer and the discussion in the links below.


What is the best diagnosis?

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Click Here To See The Answer

Answer: Paraganglioma

 


Click Here To See The Discussion

Final diagnosis:  

Paraganglioma

Educational Objectives and Discussion:

Educational Objectives

  1. Identify and describe a rare case of peripancreatic paraganglioma, a rare neoplastic disease that presents considerable diagnostic difficulty.
  2. Review the clinicopathological characteristics of peripancreatic paragangliomas.
  3. Discuss differential diagnosis of peripancreatic paragangliomas.

Discussion

Peripancreatic paragangliomas can be diagnostically challenging on small biopsies due to morphologic overlap with other primary pancreatic tumors (1, 2). In this case, an initial diagnosis of atypical epithelioid and spindle cell neoplasm was made on the biopsy and decision was made to proceed with surgery. Grossly, the resection specimen showed a 11.8 cm purple-red, ovoid, well-circumscribed peripancreatic mass surrounded by a thin fibrous capsule. Cut surface displayed a tan-pink to dark red, variegated focally nodular cut surface with multiple dilated vessels and focal areas of hemorrhage (Figure 4). Microscopic examination of the resection specimen showed neoplastic cells arranged in nests and trabeculae within a prominent vascular network (Figure 5-7). The cells were predominantly round to oval with some spindling and moderate to abundant eosinophilic granular cytoplasm. Additional IHC on the resection specimen showed that the tumor cells labeled with synaptophysin (strong), chromogranin (patchy) and S100 (patchy) and were negative for cytokeratin (Figures 8-10). In areas the S100 labeled in a sustentacular pattern (Figure 10). Succinate dehydrogenase (SDH) A and B were intact. A final diagnosis of paraganglioma was made. Subsequent blood work showed elevated plasma and urine catecholamines and molecular testing showed no targetable mutations. While the tumor was initially described radiographically as being located in the pancreatic head, subsequent imaging demonstrated a peri-pancreatic localization, much more typical of this entity. It can be critical to consider paraganglioma from both the radiographic and pathologic standpoint as repeated needle biopsies may trigger catecholamine surges and care must be taken during surgical interventions.

Figure 4. Gross appearance of resection specimen.
Figure 5. Resection, low power, H&E
Figure 6. Resection, medium power, H&E
Figure 7. Resection, high power, H&E
Figure 8. Cytokeratin immunostain, resection specimen
Figure 9. Synaptophysin immunostain, resection specimen
Figure 10. S100 immunostain, resection specimen


The classic microscopic features of paragangliomas are similar irrespective of location and include round-to-polygonal-shaped cells containing amphophilic-to-eosinophilic cytoplasm with stippled, often pleomorphic nuclei containing small inconspicuous nucleoli. In certain cases, cytoplasmic clear cell change, multinucleation, vesicular nuclei, and prominent nucleoli can also be observed (1). The tumor cells usually adopt a nested or organoid (“Zellballen”) pattern separated by highly vascularized fibrous septa. Cases with diffuse growth pattern with only focal areas of nested architecture have been reported (1). In areas of parenchymal invasion, the Zellballen growth pattern can be replaced by irregularly spaced nests of discohesive neoplastic cells. The tumor cells are synaptophysin and chromogranin positive while the surrounding sustentacular cells, label for S100. GATA3 and PHOX2B also show frequent immunoreactivity in extra-adrenal paragangliomas (3-5). Keratin is almost always negative, but rare cases have focal staining. In contrast, paragangliomas in the sacral region are typically keratin positive.


The genetic profile of paraganglioma is similar to that described for pheochromocytomas. Mutations in VHL, RET, NF1, SDHA, SDHB, SDHC, SDHD, SDHAF2, TMEM127, and MAX have been reported (6). Knowledge of these mutations may have significant impact on clinical management and patient outcome. For instance, studies have reported germline mutations in SDHB in up to 30% of patients with metastatic disease arising from sporadic paragangliomas and an association with shorter survival (1, 7, 8). Complete surgical resection of primary and
metastatic disease, when possible provides the highest chance for symptom control. Currently, there are no reliable markers to predict malignancy, except the presence of metastases. Increasing tumor size (>5 cm), increasing Ki-67 proliferation rate, SDHB mutation, and MAX mutation have been reported as risk factors for metastatic behavior (9, 10). Various scoring systems (PASS, GAPP), have been developed to predict risk in pheochromocytomas and paragangliomas (11, 12). Patients with paragangliomas ultimately require follow-up as metastatic disease can appear years after diagnosis.

Differential diagnosis:

The differential diagnosis of peripancreatic paragangliomas includes pancreatic neuroendocrine tumor (PanNET), acinar cell carcinoma (ACC), spindle cell neoplasms, PEComas, and metastatic renal cell carcinoma (RCC).Peripancreatic paragangliomas and PanNET are both neuroendocrine neoplasms thus sharing many of the same characteristics. PanNETs often show distinctive plasmacytoid morphology, usually display round and uniform nuclei and are generally positive for AE1/AE3 and CAM 5.2 while peripancreatic paragangliomas are distinctly negative. Prominent nucleoli typically seen in ACC can be present in peripancreatic paragangliomas. However, the characteristic stippled chromatin of peripancreatic paraganglioma is absent in ACC. The presence of spindle cell morphology/nuclear pleomorphism in peripancreatic paragangliomas can mimic spindle cell neoplasms. These possibilities can usually be distinguished on the basis of immunohistochemistry. Further, the nuclear pleomorphism in paragangliomas typically has a degenerative appearance. Peripancreatic paragangliomas can show cytoplasmic clear cell change thus mimicking metastatic RCCs. However, metastatic RCCs will express PAX8 and are negative for S100 and neuroendocrine
markers.

References:

  1. Singhi AD, Hruban RH, Fabre M, Imura J, Schulick R, Wolfgang C, Ali
    SZ. Peripancreatic paraganglioma: a potential diagnostic challenge in
    cytopathology and surgical pathology. Am J Surg Pathol. 2011
    Oct;35(10):1498-504. doi: 10.1097/PAS.0b013e3182281767.
    https://pubmed.ncbi.nlm.nih.gov/21921779/
  2. Zeng J, Simsir A, Oweity T, Hajdu C, Cohen S, Shi Y. Peripancreatic paraganglioma mimics pancreatic/gastrointestinal neuroendocrine tumor on fine needle aspiration: Report of two cases and review of the literature. Diagn Cytopathol. 2017 Oct;45(10):947-952. doi: 10.1002/dc.23761. https://pubmed.ncbi.nlm.nih.gov/28560856/
  3. Miettinen M, McCue PA, Sarlomo-Rikala M, Rys J, Czapiewski P, Wazny K, Langfort R, Waloszczyk P, Biernat W, Lasota J, Wang Z. GATA3: a multispecific but potentially useful marker in surgical pathology: a systematic analysis of 2500 epithelial and nonepithelial tumors. Am Surg Pathol. 2014 Jan;38(1):13-22. doi: 10.1097/PAS.0b013e3182a0218f. https://pubmed.ncbi.nlm.nih.gov/24145643/
  4. Lee JP, Hung YP, O’Dorisio TM, Howe JR, Hornick JL, Bellizzi AM. Examination of PHOX2B in adult neuroendocrine neoplasms reveals relatively frequent expression in phaeochromocytomas and paragangliomas. Histopathology. 2017 Oct;71(4):503-510. doi: 10.1111/his.13243. https://pubmed.ncbi.nlm.nih.gov/28464318/
  5. So JS, Epstein JI. GATA3 expression in paragangliomas: a pitfall potentially leading to misdiagnosis of urothelial carcinoma. Mod Pathol. 2013 Oct;26(10):1365-70. doi: 10.1038/modpathol.2013.76. https://pubmed.ncbi.nlm.nih.gov/23599157/
  6. Gimenez-Roqueplo AP, Dahia PL, Robledo M. An update on the genetics of paraganglioma, pheochromocytoma, and associated hereditary syndromes. Horm Metab Res. 2012 May;44(5):328-33. doi: 10.1055/s-0031-1301302. https://pubmed.ncbi.nlm.nih.gov/22328163/
  7. Brouwers FM, Eisenhofer G, Tao JJ, Kant JA, Adams KT, Linehan WM, Pacak K. High frequency of SDHB germline mutations in patients with malignant catecholamine-producing paragangliomas: implications for genetic testing. J Clin Endocrinol Metab. 2006 Nov;91(11):4505-9. doi: 10.1210/jc.2006-0423. https://pubmed.ncbi.nlm.nih.gov/16912137/
  8. Amar L, Baudin E, Burnichon N, Peyrard S, Silvera S, Bertherat J, Bertagna X, Schlumberger M, Jeunemaitre X, Gimenez-Roqueplo AP, Plouin PF. Succinate dehydrogenase B gene mutations predict survival in patients with malignant pheochromocytomas or paragangliomas. J Clin Endocrinol Metab. 2007 Oct;92(10):3822-8. doi: 10.1210/jc.2007-0709. https://pubmed.ncbi.nlm.nih.gov/17652212/
  9. Kimura N, Takayanagi R, Takizawa N, Itagaki E, Katabami T, Kakoi N, Rakugi H, Ikeda Y, Tanabe A, Nigawara T, Ito S, Kimura I, Naruse M; Phaeochromocytoma Study Group in Japan. Pathological grading for predicting metastasis in phaeochromocytoma and paraganglioma. Endocr Relat Cancer. 2014 May 6;21(3):405-14. doi: 10.1530/ERC-13-0494. https://pubmed.ncbi.nlm.nih.gov/24521857/
  10. Assadipour Y, Sadowski SM, Alimchandani M, Quezado M, Steinberg SM, Nilubol N, Patel D, Prodanov T, Pacak K, Kebebew E. SDHB mutation status and tumor size but not tumor grade are important predictors of clinical outcome in pheochromocytoma and abdominal paraganglioma. Surgery. 2017 Jan;161(1):230-239. doi: 10.1016/j.surg.2016.05.050. https://pubmed.ncbi.nlm.nih.gov/27839933/
  11. Kimura N, Takekoshi K, Naruse M. Risk Stratification on Pheochromocytoma and Paraganglioma from Laboratory and Clinical Medicine. J Clin Med. 2018. Sep; 7(9): 242. https://pubmed.ncbi.nlm.nih.gov/30150569/
  12. Thompson LD. Pheochromocytoma of the Adrenal gland Scaled Score (PASS) to separate benign from malignant neoplasms: a clinicopathologic and immunophenotypic study of 100 cases. Am J Surg Pathol. 2002 May;26(5):551-66. doi: 10.1097/00000478-200205000-00002. https://pubmed.ncbi.nlm.nih.gov/11979086/


Case contributed by:

Oluwaseyi Olayinka, MD, MSc, Danbury Hospital

Ramapriya Vidhun, MD, Danbury Hospital

Conflict of Interest: NO

 

The Pancreatobiliary Pathology Society is seeking new Committee Members.

The PBPath Website/Membership committee is seeking new committee members to join our team, for a term of 3 years.
The website/membership team member(s) will help the Pancreatobiliary Pathology Society maintain and expand our membership, post updates to our website, and send newsletters to our members. Experience with WordPress and/or HTML is a plus, but not required.

The ideal candidates possess a willingness to learn and a team-player mentality.

Interested PBPath members should send CV to info@pbpath.org. Successful committee members must be active members of the Pancreatobiliary Pathology Society.

The Pancreatobiliary Pathology Society Executive Committee

Case 4: Quarter 3, 2021

Clinical History

A 2-year-old-baby presented as a transfer from an outside hospital (OSH) due to concerns for possible acute cholecystitis. The patient has a history of abdominal pain for the last 2 weeks. The laboratory tests from the OSH were notable for leukocytosis. An abdominal CT scan showed a thickened gallbladder wall with numerous polypoid, non-mobile lesions. Eventually, the patient underwent laparoscopic cholecystectomy.

Macroscopic Description
On gross examination, the gallbladder measured 8.8 x 1.5 x 1.2 cm, with multiple, scattered polypoid mucosal lesions mainly in the body and fundus. The largest lesion measured 2 cm in the greatest dimension (arrows) (Figure 1). No cholelithiasis was present.

Figure 1. Gross photograph of the gallbladder showing polypoid exophytic lesions on the mucosa.

Histologic/Cytologic Features 

Microscopic pictures of the gallbladder lesions are shown in Figures 2-4. As shown in Figure 2, The lesions had an intraluminal exophytic (mass-forming) growth pattern and papillary architecture (black arrows). Adjacent mucosa (white arrows) is also involved by papillary overgrowth of epithelium. Figure 3 showed that the neoplastic epithelial lining is composed of a combination of biliary (black arrow), gastric foveolar-type (white arrow), and intestinal-type epithelium with goblet cells (blue arrow). No high grade cytologic atypia or architectural abnormalities were identified. A higher-power image is shown in Figure 4 and highlights a collection of the lamina propria macrophages (black arrows).

Figure 2. Low-power view of the exophytic lesion, H&E stain.
Figure 3. Medium-power view of the exophytic lesion, H&E stain.
Figure 4. High-power view of the lamina propria of the lesion, H&E stain.

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Please select your diagnosis in the poll, then see the answer and the discussion in the links below.

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What is the diagnosis of the lesion?

View Results

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Answer: Intracholecystic papillary neoplasm

Final diagnosis:  

Intracholecystic papillary neoplasm

Educational Objectives and Discussion:

Educational Objectives

  1. To understand the definition of intracholecystic papillary neoplasm
    (ICPN) of the gallbladder by 2019 WHO Digestive System Tumours.
  2. To recognize the gallbladder lesions associated with metachromatic
    leukodystrophy (MLD), an unusual neurologic disease in pediatric patients.
  3. To discuss the differential diagnosis of ICPN.

Discussion

Intracholecystic papillary neoplasm (ICPN) is a precancerous lesion of the gallbladder. Per the 2019 WHO Digestive System Tumours [1], ICPN encompasses/replaces the previous terminologies, including biliary
adenoma, tubulopapillary adenoma, intracystic papillary neoplasm, and papillomatosis. Grossly, these tumors form distinct polypoid/exophytic intraluminal masses that are grossly visible. Microscopically, these tumors show papillary and/or tubular configuration with varying degrees of epithelial dysplasia. There are four morphologic patterns recognized: biliary, intestinal, gastric, oncocytic, or combination of these. These morphologic patterns contrast with classifications of intraductal papillary mucinous neoplasms (IPMN) of the pancreas in which oncocytic lesions (intraductal oncocytic papillary neoplasms (IOPN)) have been separated from IPMN due to distinct molecular findings. Mucosa surrounding ICPN may demonstrate dysplasia as well. About 50% of ICPNs are associated with invasive adenocarcinoma, but they have a better clinical outcome than conventional gallbladder adenocarcinomas [1, 2].

Our case exhibited low-grade ICPN with combined biliary, gastric, and intestinal differentiation. Adjacent mucosa also showed diffuse low-grade dysplasia. No high-grade dysplasia or invasive carcinoma was identified in extensively submitted sections. The aforementioned unusual findings in the gallbladder from a 2-year-old baby triggered further work-up since there is a well-known association between ICPN (previously called gallbladder papillomatosis) and metachromatic leukodystrophy (MLD) [3-5]. Genetic analysis was performed and the results revealed homozygous deletion of pathogenic variant c.1283C>T (p.Pro428Leu) in ARSA gene, which is associated with MLD. Brain MRI findings were non-specific and she has no history of developmental delay, neurologic symptoms, or regression.

MLD is a lysosomal storage disease caused by a deficiency of arylsulfatase A (ASA) with autosomal recessive inheritance in most cases. The ASA deficiency leads to the accumulation of sulfatides in the central and peripheral nervous system, which results in the destruction of the myelin sheath and eventually leads to neurologic symptoms such as seizures, loss of motor functions, and peripheral neuropathy [6]. Sufatide accumulation is also detected in other organs, e.g., the gallbladder, kidney, lymph nodes, liver, and bone marrow. The gallbladder epithelial cells and macrophages contain cytoplasmic inclusions on electron microscopic examination, consistent with sulfatide accumulation [3, 7]. Almost all case reports described the presence of collections of the lamina propria macrophages in the gallbladder [3, 4, 7, 8], as seen in our case (Figure 4). This accumulation of macrophages could show histologic overlap with cholesterolosis, a more common finding in the gallbladder. In MLD, Giemsa and toluidine blue stains will show metachromasia of the cytoplasm of macrophages, consistent with the accumulation of sulfatide deposits. In contrast, the accumulation of cholesterol esters and triglycerides can be highlighted on frozen tissue with Oil red O or Sudan black stains.

According to the age of disease onset, there are three clinical subtypes of MLD, including late infantile-onset, juvenile-onset, and adult-onset. Our patient showed no neurologic symptoms but was homozygous for mutation of the ARSA gene, which encodes ASA. Numerous mutations in the ARSA gene have been identified, and c.1283C_T mutation in our case is usually seen in juvenile or adult-onset phenotype [6]. That may explain the neurologic symptom-free status of our patient. A possible treatment for MLD so far is hematopoietic stem cell transplantation for selected cases [4]. MLD-associated gallbladder abnormalities occasionally appear before the onset of neurologic symptoms or an MLD diagnosis [3]. One case series with 34 patients reported that 76% of MLD patients showed gallbladder involvement [4]. The gallbladder abnormalities consist of benign and malignant conditions, e.g., cholecystitis, cholelithiasis, mucosal hyperplasia, polypoid lesions (now most lesions are under the category of ICPN), and adenocarcinoma [3-5]. In conclusion, gallbladder abnormalities, in particular polypoid lesions, are rare during childhood. This condition can be seen in cases with MLD, Peutz-Jeghers’ syndrome, and pancreaticobiliary malunion [8]. Pathologists should pay close attention to unusual gallbladder abnormalities in pediatric and adolescent patients to consider the above-mentioned possibilities and associated risk of malignancy.

Differential diagnosis:

Pyloric gland adenoma is composed of lobules of small, tightly packed, bland-looking glands that are morphologically similar to pyloric or Brunner glands. The uninvolved gallbladder mucosa is mostly devoid of dysplasia or pyloric gland metaplasia. Of note, pyloric gland nodules <0.5 cm arising in a background of pyloric gland metaplasia should not be designated as pyloric gland adenoma [9].
Reactive epithelial hyperplasia, commonly due to secondary causes (e.g., cholelithiasis, chronic cholecystitis, inflammatory bowel disease, primary sclerosing cholangitis), shows focal or diffuse papillary-shaped and elongated mucosal folds lined by bland epithelial cells with or without metaplastic changes. The presence of significant inflammation and no discrete, grossly visible mass-forming lesion, may help distinguish reactive hyperplasia from ICPN [1,10].
Invasive adenocarcinoma is present in about 50% of the ICPN cases at the time of diagnosis [2]. Gallbladder adenocarcinoma arising in ICPN is more commonly associated with papillary growth patterns, biliary epithelial lineage, and high-grade dysplasia. The invasive component is often a tubular adenocarcinoma, although other types, such as mucinous, adenosquamous, or neuroendocrine carcinoma, have also been reported. Extensive sampling is warranted because approximately 60% of ICPN with carcinoma showed ≤ 5mm of invasive focus, and the carcinoma may also occur away from the main ICPN lesion. Some patients with non-invasive ICPN can also die of new primary carcinoma in the biliary tract, typically long after the diagnosis of ICPN, possibly due to the field cancerization phenomenon. This observation supports long-term surveillance of these patients with ICPN even after resection [1, 2].

References:

  1. Basturk O, Aishima S, Esoposito I. World Health Organization Classification of Tumours. Intracholecystic papillary neoplasm. In: Digestive System Tumours. 2019, IARC, Lyon.
  2. Adsay V, Jang KT, Roa JC, Dursun N, Ohike N, Bagci P, Basturk O, Bandyopadhyay S, Cheng JD, Sarmiento JM, Escalona OT, Goodman M, Kong SY, Terry P. Intracholecystic papillary-tubular neoplasms (ICPN) of
    the gallbladder (neoplastic polyps, adenomas, and papillary neoplasms that are ≥1.0 cm): clinicopathologic and immunohistochemical analysis of 123 cases. Am J Surg Pathol. 2012 Sep;36(9):1279-301.
  3. McFadden K, Ranganathan S. Pathology of the gallbladder in a child with metachromatic leukodystrophy. Pediatr Dev Pathol. 2015 May-Jun;18(3):228-30.
  4. van Rappard DF, Bugiani M, Boelens JJ, van der Steeg AF, Daams F, de Meij TG, van Doorn MM, van Hasselt PM, Gouma DJ, Verbeke JI, Hollak CE, van Hecke W, Salomons GS, van der Knaap MS, Wolf NI. Gallbladder
    and the risk of polyps and carcinoma in metachromatic leukodystrophy. Neurology. 2016 Jul 5;87(1):103-11.
  5. Kim J, Sun Z, Ezekian B, Schooler GR, Prasad VK, Kurtzberg J, Rice HE, Tracy ET. Gallbladder abnormalities in children with metachromatic leukodystrophy. J Surg Res. 2017 Feb;208:187-191.
  6. Cesani M, Lorioli L, Grossi S, Amico G, Fumagalli F, Spiga I, Filocamo M, Biffi A. Mutation Update of ARSA and PSAP Genes Causing Metachromatic Leukodystrophy. Hum Mutat. 2016 Jan;37(1):16-27.
  7. Rodriguez-Waitkus PM, Byrd R, Hicks J. Metachromatic leukodystrophy and its effects on the gallbladder: a case report. Ultrastruct Pathol. 2011 Dec;35(6):271-6.
  8. Garavelli L, Rosato S, Mele A, Wischmeijer A, Rivieri F, Gelmini C, Sandonà F, Sassatelli R, Carlinfante G, Giovanardi F, Gemmi M, Della Giustina E, Amarri S, Banchini G, Bedogni G. Massive hemobilia and
    papillomatosis of the gallbladder in metachromatic leukodystrophy: a life-threatening condition. Neuropediatrics. 2009 Dec;40(6):284-6.
  9.  Basturk O, Aishima S, Esoposito I. World Health Organization Classification of Tumours. Pyloric gland adenoma of the gallbladder. In: Digestive System Tumours. 2019, IARC, Lyon.
  10. Umudum H, Gunbatili E, Sanal M, Ceyhan K. Primary diffuse papillary hyperplasia of the gallbladder. Pathology. 2006 Dec;38(6):591-2.

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Case contributed by:

Goo Lee, MD, PhD. University of Alabama at Birmingham

Rong Li, MD, PhD. Children’s of Alabama Benjamin Russell Hospital For Children

Conflict of Interest: NO

Case 4: Quarter 3, 2021

Case 4: Quarter 3, 2021

Clinical History

A 2-year-old-baby presented as a transfer from an outside hospital (OSH) due to concerns for possible acute cholecystitis. The patient has a history of abdominal pain for the last 2 weeks. The laboratory tests from the OSH were notable for leukocytosis. An abdominal CT scan showed a thickened gallbladder wall with numerous polypoid, non-mobile lesions. Eventually, the patient underwent laparoscopic cholecystectomy.

Macroscopic Description
On gross examination, the gallbladder measured 8.8 x 1.5 x 1.2 cm, with multiple, scattered polypoid mucosal lesions mainly in the body and fundus. The largest lesion measured 2 cm in the greatest dimension (arrows) (Figure 1). No cholelithiasis was present.

Figure 1. Gross photograph of the gallbladder showing polypoid exophytic lesions on the mucosa.

Histologic/Cytologic Features 

Microscopic pictures of the gallbladder lesions are shown in Figures 2-4. As shown in Figure 2, The lesions had an intraluminal exophytic (mass-forming) growth pattern and papillary architecture (black arrows). Adjacent mucosa (white arrows) is also involved by papillary overgrowth of epithelium. Figure 3 showed that the neoplastic epithelial lining is composed of a combination of biliary (black arrow), gastric foveolar-type (white arrow), and intestinal-type epithelium with goblet cells (blue arrow). No high grade cytologic atypia or architectural abnormalities were identified. A higher-power image is shown in Figure 4 and highlights a collection of the lamina propria macrophages (black arrows).

Figure 2. Low-power view of the exophytic lesion, H&E stain.
Figure 3. Medium-power view of the exophytic lesion, H&E stain.
Figure 4. High-power view of the lamina propria of the lesion, H&E stain.

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Please select your diagnosis in the poll, then see the answer and the discussion in the links below.

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What is the diagnosis of the lesion?

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Answer: Intracholecystic papillary neoplasm

 

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Final diagnosis:  

Intracholecystic papillary neoplasm

Educational Objectives and Discussion:

Educational Objectives

  1. To understand the definition of intracholecystic papillary neoplasm
    (ICPN) of the gallbladder by 2019 WHO Digestive System Tumours.
  2. To recognize the gallbladder lesions associated with metachromatic
    leukodystrophy (MLD), an unusual neurologic disease in pediatric patients.
  3. To discuss the differential diagnosis of ICPN.

Discussion

Intracholecystic papillary neoplasm (ICPN) is a precancerous lesion of the gallbladder. Per the 2019 WHO Digestive System Tumours [1], ICPN encompasses/replaces the previous terminologies, including biliary
adenoma, tubulopapillary adenoma, intracystic papillary neoplasm, and papillomatosis. Grossly, these tumors form distinct polypoid/exophytic intraluminal masses that are grossly visible. Microscopically, these tumors show papillary and/or tubular configuration with varying degrees of epithelial dysplasia. There are four morphologic patterns recognized: biliary, intestinal, gastric, oncocytic, or combination of these. These morphologic patterns contrast with classifications of intraductal papillary mucinous neoplasms (IPMN) of the pancreas in which oncocytic lesions (intraductal oncocytic papillary neoplasms (IOPN)) have been separated from IPMN due to distinct molecular findings. Mucosa surrounding ICPN may demonstrate dysplasia as well. About 50% of ICPNs are associated with invasive adenocarcinoma, but they have a better clinical outcome than conventional gallbladder adenocarcinomas [1, 2].

Our case exhibited low-grade ICPN with combined biliary, gastric, and intestinal differentiation. Adjacent mucosa also showed diffuse low-grade dysplasia. No high-grade dysplasia or invasive carcinoma was identified in extensively submitted sections. The aforementioned unusual findings in the gallbladder from a 2-year-old baby triggered further work-up since there is a well-known association between ICPN (previously called gallbladder papillomatosis) and metachromatic leukodystrophy (MLD) [3-5]. Genetic analysis was performed and the results revealed homozygous deletion of pathogenic variant c.1283C>T (p.Pro428Leu) in ARSA gene, which is associated with MLD. Brain MRI findings were non-specific and she has no history of developmental delay, neurologic symptoms, or regression.

MLD is a lysosomal storage disease caused by a deficiency of arylsulfatase A (ASA) with autosomal recessive inheritance in most cases. The ASA deficiency leads to the accumulation of sulfatides in the central and peripheral nervous system, which results in the destruction of the myelin sheath and eventually leads to neurologic symptoms such as seizures, loss of motor functions, and peripheral neuropathy [6]. Sufatide accumulation is also detected in other organs, e.g., the gallbladder, kidney, lymph nodes, liver, and bone marrow. The gallbladder epithelial cells and macrophages contain cytoplasmic inclusions on electron microscopic examination, consistent with sulfatide accumulation [3, 7]. Almost all case reports described the presence of collections of the lamina propria macrophages in the gallbladder [3, 4, 7, 8], as seen in our case (Figure 4). This accumulation of macrophages could show histologic overlap with cholesterolosis, a more common finding in the gallbladder. In MLD, Giemsa and toluidine blue stains will show metachromasia of the cytoplasm of macrophages, consistent with the accumulation of sulfatide deposits. In contrast, the accumulation of cholesterol esters and triglycerides can be highlighted on frozen tissue with Oil red O or Sudan black stains.

According to the age of disease onset, there are three clinical subtypes of MLD, including late infantile-onset, juvenile-onset, and adult-onset. Our patient showed no neurologic symptoms but was homozygous for mutation of the ARSA gene, which encodes ASA. Numerous mutations in the ARSA gene have been identified, and c.1283C_T mutation in our case is usually seen in juvenile or adult-onset phenotype [6]. That may explain the neurologic symptom-free status of our patient. A possible treatment for MLD so far is hematopoietic stem cell transplantation for selected cases [4]. MLD-associated gallbladder abnormalities occasionally appear before the onset of neurologic symptoms or an MLD diagnosis [3]. One case series with 34 patients reported that 76% of MLD patients showed gallbladder involvement [4]. The gallbladder abnormalities consist of benign and malignant conditions, e.g., cholecystitis, cholelithiasis, mucosal hyperplasia, polypoid lesions (now most lesions are under the category of ICPN), and adenocarcinoma [3-5]. In conclusion, gallbladder abnormalities, in particular polypoid lesions, are rare during childhood. This condition can be seen in cases with MLD, Peutz-Jeghers’ syndrome, and pancreaticobiliary malunion [8]. Pathologists should pay close attention to unusual gallbladder abnormalities in pediatric and adolescent patients to consider the above-mentioned possibilities and associated risk of malignancy.

Differential diagnosis:

Pyloric gland adenoma is composed of lobules of small, tightly packed, bland-looking glands that are morphologically similar to pyloric or Brunner glands. The uninvolved gallbladder mucosa is mostly devoid of dysplasia or pyloric gland metaplasia. Of note, pyloric gland nodules <0.5 cm arising in a background of pyloric gland metaplasia should not be designated as pyloric gland adenoma [9].
Reactive epithelial hyperplasia, commonly due to secondary causes (e.g., cholelithiasis, chronic cholecystitis, inflammatory bowel disease, primary sclerosing cholangitis), shows focal or diffuse papillary-shaped and elongated mucosal folds lined by bland epithelial cells with or without metaplastic changes. The presence of significant inflammation and no discrete, grossly visible mass-forming lesion, may help distinguish reactive hyperplasia from ICPN [1,10].
Invasive adenocarcinoma is present in about 50% of the ICPN cases at the time of diagnosis [2]. Gallbladder adenocarcinoma arising in ICPN is more commonly associated with papillary growth patterns, biliary epithelial lineage, and high-grade dysplasia. The invasive component is often a tubular adenocarcinoma, although other types, such as mucinous, adenosquamous, or neuroendocrine carcinoma, have also been reported. Extensive sampling is warranted because approximately 60% of ICPN with carcinoma showed ≤ 5mm of invasive focus, and the carcinoma may also occur away from the main ICPN lesion. Some patients with non-invasive ICPN can also die of new primary carcinoma in the biliary tract, typically long after the diagnosis of ICPN, possibly due to the field cancerization phenomenon. This observation supports long-term surveillance of these patients with ICPN even after resection [1, 2].

References:

  1. Basturk O, Aishima S, Esoposito I. World Health Organization Classification of Tumours. Intracholecystic papillary neoplasm. In: Digestive System Tumours. 2019, IARC, Lyon.
  2. Adsay V, Jang KT, Roa JC, Dursun N, Ohike N, Bagci P, Basturk O, Bandyopadhyay S, Cheng JD, Sarmiento JM, Escalona OT, Goodman M, Kong SY, Terry P. Intracholecystic papillary-tubular neoplasms (ICPN) of
    the gallbladder (neoplastic polyps, adenomas, and papillary neoplasms that are ≥1.0 cm): clinicopathologic and immunohistochemical analysis of 123 cases. Am J Surg Pathol. 2012 Sep;36(9):1279-301.
  3. McFadden K, Ranganathan S. Pathology of the gallbladder in a child with metachromatic leukodystrophy. Pediatr Dev Pathol. 2015 May-Jun;18(3):228-30.
  4. van Rappard DF, Bugiani M, Boelens JJ, van der Steeg AF, Daams F, de Meij TG, van Doorn MM, van Hasselt PM, Gouma DJ, Verbeke JI, Hollak CE, van Hecke W, Salomons GS, van der Knaap MS, Wolf NI. Gallbladder
    and the risk of polyps and carcinoma in metachromatic leukodystrophy. Neurology. 2016 Jul 5;87(1):103-11.
  5. Kim J, Sun Z, Ezekian B, Schooler GR, Prasad VK, Kurtzberg J, Rice HE, Tracy ET. Gallbladder abnormalities in children with metachromatic leukodystrophy. J Surg Res. 2017 Feb;208:187-191.
  6. Cesani M, Lorioli L, Grossi S, Amico G, Fumagalli F, Spiga I, Filocamo M, Biffi A. Mutation Update of ARSA and PSAP Genes Causing Metachromatic Leukodystrophy. Hum Mutat. 2016 Jan;37(1):16-27.
  7. Rodriguez-Waitkus PM, Byrd R, Hicks J. Metachromatic leukodystrophy and its effects on the gallbladder: a case report. Ultrastruct Pathol. 2011 Dec;35(6):271-6.
  8. Garavelli L, Rosato S, Mele A, Wischmeijer A, Rivieri F, Gelmini C, Sandonà F, Sassatelli R, Carlinfante G, Giovanardi F, Gemmi M, Della Giustina E, Amarri S, Banchini G, Bedogni G. Massive hemobilia and
    papillomatosis of the gallbladder in metachromatic leukodystrophy: a life-threatening condition. Neuropediatrics. 2009 Dec;40(6):284-6.
  9.  Basturk O, Aishima S, Esoposito I. World Health Organization Classification of Tumours. Pyloric gland adenoma of the gallbladder. In: Digestive System Tumours. 2019, IARC, Lyon.
  10. Umudum H, Gunbatili E, Sanal M, Ceyhan K. Primary diffuse papillary hyperplasia of the gallbladder. Pathology. 2006 Dec;38(6):591-2.

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Case contributed by:

Goo Lee, MD, PhD. University of Alabama at Birmingham

Rong Li, MD, PhD. Children’s of Alabama Benjamin Russell Hospital For Children

Conflict of Interest: NO

Case 3: Quarter 2, 2021

Case 3: Quarter 2, 2021

Clinical History

A 50-year-old woman with no significant past medical history presented with abdominal pain and a syncopal episode. Abdominal MRI showed a multicystic mass with a significant solid component in the pancreatic tail, measuring 2.2 cm in the greatest dimension. A fine-needle biopsy of the lesion was performed.

Histologic/Cytologic Features 

Microscopic pictures of the biopsy are shown in Figures 1-5. The histologic examination revealed a spindle cell lesion. The cells had relatively uniform and elongated nuclei, and some had vesicular chromatin with conspicuous nucleoli; others appeared wavy and hyperchromatic. No significant nuclear atypia or mitotic activity was present. Background normal pancreatic parenchyma was also identified.

Figure. 1-3. 1. H&E stain of the tumor, 4X; 2. H&E stain of the tumor, 10X; 3. H&E stain of the tumor, 10X
Figure. 4-5. 4. H&E stain of the tumor, 20X; 5. H&E stain of the tumor, 20X

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Please select your diagnosis in the poll, then see the answer and the discussion in the links below.

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What is the diagnosis of the lesion?

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Click Here To See The Answer

Answer: Mucinous cystic neoplasm

 

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Click Here To See The Discussion

Final diagnosis:  

Mucinous cystic neoplasm

Educational Objectives and Discussion:

Educational Objectives

  1. Discuss spindle cell lesions of the pancreas.
  2. Review the clinicopathological characteristics of mucinous cystic neoplasms of the pancreas.
  3. Identify an unusual presentation of mucinous cystic neoplasms with stromal overgrowth.

Discussion

Immunohistochemistry stains were performed, and the spindle cells were positive for estrogen and progesterone receptors (Figures 6-7) and focally positive for inhibin. The spindle cells were negative for CD117, DOG1, S100, pan-cytokeratin, and beta-catenin. The proliferation index assessed with Ki-67 was approximately 1%. Based on the lesion’s morphology and immunoprofile, the case was diagnosed as mucinous/non-mucinous cystic neoplasm with ovarian-type stroma.

Figure. 6-7. 6. Immunohistochemical stain for estrogen receptor, 20X; 7. Immunohistochemical stain for progesterone receptor, 20X

After the diagnosis, distal pancreatectomy and splenectomy were performed. Grossly, there was a 2.2 x 1.6 x 1.6 cm partially cystic well-circumscribed mass in the pancreatic tail containing thick clear fluid (Figure 8). Serial sections showed a 60% cystic and a 40% solid component. The mass showed no communication with the pancreatic ductal system.

Figure. 8. Gross photograph of the cystic lesion at the tail of the pancreas

Microscopic pictures of the resection are shown in Figures 9 – 11. The histologic examination revealed multiple cysts lined by a single layer of cuboidal cells that lacked mucin and had abundant eosinophilic cytoplasm. A prominent densely packed spindle cell-rich stroma was identified. The spindle cells had elongated nuclei with fine chromatin and inconspicuous nucleoli. No malignant features were present.

9-11. 9. H&E stain of the tumor in resection specimen, 10X; 10. H&E stain of the tumor in resection specimen, 10X; 11. H&E stain of the tumor in resection specimen,

Pancreatic mucinous/non-mucinous cystic neoplasm (MCN) is an epithelial tumor typically associated with ovarian-type stroma. The majority of these lesions are found in the body or tail of the pancreas, occur in women, and have a mean age at diagnosis of 48 years old (1). Clinically, patients with MCN present with abdominal discomfort or epigastric pain, while others may be asymptomatic, and the tumor is found incidentally (2).

The histogenesis of these lesions is still in debate. Some proposed hypotheses suggest that the mesenchymal component derives from ectopic ovarian stroma incorporated during embryogenesis in the pancreas or represents persistent fetal periductal mesenchyme under hormonal stimulation (1).

Grossly, MCN usually presents with large unilocular or multilocular cysts, filled with thick gelatinous material, and lacks communication between the cyst and the pancreatic ductal system (3). Microscopically, the cysts are lined by mucin-producing columnar cells with varying degrees of cytologic and architectural atypia. However, cuboidal cells with no mucin can also occur. Based on the level of atypia, MCNs are further categorized as MCN with low- or high-grade dysplasia. The stromal component, called “ovarian-type stroma,” forms bands of densely packed spindle cells amongst the cysts, and its presence is required for the diagnosis. Typically, the stroma represents a smaller constituent of the lesion, and in some cases, it is difficult to identify as it can become hypocellular and replaced by hyalinized tissue (3). The epithelial cells stain positive with CK7 and MUC5AC. The ovarian-type stroma expresses PR (60-90%), ER (30%), SMA, and desmin. Luteinized cells can stain for inhibin and calretinin (1).

Molecularly, most MCN epitheliums carry activating mutations in codon 12 of KRAS (50-66%), some can carry loss-of-function mutations in RNF43 (1).

The case reported here has a very unusual presentation, given the fact that the stroma represents the predominant component of the lesion. The subepithelial stroma in this lesion was cellular and composed of cytologically bland spindle cells mimicking ovarian-type stroma without any malignant features. To our knowledge, this rare presentation of MCN has only been reported twice in the literature (4-5).

Molecular studies have shown frequent mutations in ID3, ARID1A, APC, and CDKN2A tumor suppressor genes in ACC (5-7). TP53 mutation or deletion has been identified in 12-24% of ACC (5,6). About 23% of ACC harbor gene fusion involving BRAF and RAF1 with the most common fusions being SND1-BRAF and HERPUD1-BRAF (5). These tumors are more sensitive to MEK inhibitors. In addition, microsatellite instability has been found in 8-14% of ACC (8,9).

Differential diagnosis:

The specimen was composed predominantly of bland-looking stroma on the initial biopsy, lacking a prominent epithelial component. Hence the initial differential diagnosis of this case comprises MCNs with sarcomatous stroma, carcinosarcoma, and benign mesenchymal tumors.

MCNs with sarcomatous stroma are infrequent and have been reported more frequently in the tail of the pancreas (6). The sarcomatous component is hypercellular, contains mitotic figures, and shows atypia and pleomorphism, in contrast with the bland looking stroma of the typical MCN.

Carcinosarcoma of the pancreas is a neoplasm composed of malignant mixed epithelial and mesenchymal elements (7). The sarcomatous component is composed of highly cellular areas with pleomorphic spindle cells containing abundant cytoplasm, hyperchromatic nuclei, and prominent nucleoli. Occasional bizarre cells can be identified. The histogenesis of this tumor remains unclear.

Benign mesenchymal tumors of the pancreas are extremely rare; some examples include inflammatory myofibroblastic tumor, extra gastrointestinal stromal tumor (GIST), schwannoma, and solitary fibrous tumor (SFT). Very few cases of pancreatic SFT have been reported in the literature. In the present case, the stroma did not show prominent staghorn-like vascularization, or a short storiform arrangement of the spindle cells, characteristics of SFT (8). Inflammatory myofibroblastic tumors could also be excluded based on the absence of a significant chronic inflammatory cell component. Primary GIST of the pancreas has been reported, showing the typical morphologic characteristics of the uniform spindle or epithelioid cells arranged in short fascicles or whorls (9). Differential diagnosis between MCN stroma and these mesenchymal tumors is based on histology and immunohistochemistry findings. The immunoprofile of the ovarian-type stroma of MCNs, showing positivity for inhibin, calretinin, estrogen and progesterone receptors, is not shared by these benign mesenchymal lesions. GIST is positive for c-kit and DOG1, schwannoma for S100, and SFT for STAT6 and CD34.

Finally, in the resection specimen, intraductal papillary mucinous neoplasms (IPMNs) should be considered in the differential diagnosis. IPMNs are characterized by cystic dilatation of pancreatic ducts in which an intraductal proliferation of neoplastic mucin-producing cells is arranged in a papillary pattern. IPMNs do not contain the ovarian-type stroma that characterizes the MCN (10).

References:

  1. Basturk O, Esposito I, Fukushima N et al. Pancreatic mucinous cystic neoplasm. In: Board WCoTE, ed. WHO Classification of Tumours: Digestive System Tumours. 5th ed. Lyon, France: IARC Press; 2019:319-321.
  2. Fukushima N, Fukayama M. Mucinous cystic neoplasms of the pancreas: pathology and molecular genetics. J Hepatobiliary Pancreat Surg. 2007;14(3):238-42.
  3. Jang KT, Park SM, Basturk O, Bagci P, Bandyopadhyay S, Stelow EB, Walters DM, Choi DW, Choi SH, Heo JS, Sarmiento JM, Reid MD, Adsay V. Clinicopathologic characteristics of 29 invasive carcinomas arising in 178 pancreatic mucinous cystic neoplasms with ovarian-type stroma: implications for management and prognosis. Am J Surg Pathol. 2015;39(2):179-87.
  4. Handra-Luca A, Couvelard A, Sauvanet A, Fléjou JF, Degott C. Mucinous cystadenoma with mesenchymal over-growth: a new variant among pancreatic mucinous cystadenomas? Virchows Arch. 2004;445(2):203-
  5. Lee WA. Mucinous cystadenoma of the pancreas with predominant stroma creating a solid tumor. World J Surg Oncol. 2005; 3:59.
  6. Van den Berg W, Tascilar M, Offerhaus GJ, Albores-Saavedra J, Wenig BM, Hruban RH, Gabrielson E. Pancreatic mucinous cystic neoplasms with sarcomatous stroma: molecular evidence for monoclonal origin with subsequent divergence of the epithelial and sarcomatous components. Mod Pathol. 2000;13(1):86-91.
  7. Farbod Darvishian, James Sullivan, Saul Teichberg, Kevin Basham; Carcinosarcoma of the Pancreas: A Case Report and Review of the Literature. Arch Pathol Lab Med. 2002; 126 (9):1114–1117.
  8. Baxter AR, Newman E, Hajdu CH. Solitary fibrous tumor of the pancreas. J Surg Case Rep. 2015; (12): rjv144.
  9. Trabelsi A, Yacoub-Abid LB, Mtimet A, et al. Gastrointestinal stromal tumor of the pancreas: A case report and review of the literature. N Am J Med Sci. 2009;1(6):324-326.
  10. Basturk O, Esposito I, Fukushima N et al. Pancreatic intraductal papillary mucinous neoplasm. In: Board WCoTE, ed. WHO Classification of Tumours: Digestive System Tumours. Lyon, France: IARC Press; 2019:310-314.

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Case contributed by:

Julia A. Gallardo, M.D.

Sadhna Dhingra, M.D.

Department of Pathology and Immunology, Baylor College of Medicine

Conflict of Interest: NO

2021 PBPath Business Meeting agenda/minutes

Pancreatobiliary Pathology Society Members,

Alas, we will not be able to meet in person this year, therefore please find attached the 2021 Pancreatobiliary Pathology Society (PBPS) Annual Business meeting agenda/minutes for your review to learn what PBPS has accomplished: PBPath Business Meeting 2021

Two requests:
1. Listen to our PBPS Companion meeting speakers, submit your questions and attend the LIVE Question and Answer on Tuesday March 16, 2021 11-11:30 AM PST
2. Vote for our new member before March 20, 2021 (will only take 1 minute) https://www.surveymonkey.com/r/7PWVKV5

Can’t wait to see all of you in person next year!

Most appreciatively,
Grace E. Kim
Pancreatobiliary Pathology Society Secretary/Treasurer