Genomic characterization of undifferentiated sarcomatoid carcinoma of the pancreas

Gkountakos, Anastasios; Mafficini, Andrea; Lou, Emil; Malleo, Giuseppe; Salvia, Roberto; Calicchia, Martina; Silvestris, Nicola; Racila, Emilian; Amin, Khalid; Veronese, Nicola; Brunetti, Oronzo; Antonini, Pietro; Ingravallo, Giuseppe; Mattiolo, Paola; Saponaro, Concetta; Nappo, Floriana; Simbolo, Michele; Bariani, Elena; Fassan, Matteo; Milella, Michèle; Lawlor, Rita T.; Scarpa, Aldo; Luchini, Claudio

doi:10.1016/j.humpath.2022.07.011

Cited by 9 publications

(5 citation statements)

References 32 publications

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“…13 A recent study by Gkountakos et al reported NGS findings in 10 patients with undifferentiated sarcomatoid carcinoma of the pancreas and found genetic alterations similar to those seen in conventional ductal adenocarcinoma, including KRAS, TP53, and CDKN2A mutations in 100%, 90%, and 60% of cases (7 of 10 cases only harbored these mutations). 14 One case also showed a SMAD4 mutation and MCL1 amplification, and another case with lung metastases showed POLQ mutations in both the primary and metastatic tumors.…”

Section: Discussion/conclusionmentioning

confidence: 94%

Cytologic, histologic, and molecular features of pancreatic sarcomatoid undifferentiated carcinoma with heterologous osteosarcomatous transformation

Zhang

Sabatino

Castillo

et al. 2023

Diagnostic Cytopathology

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Fine‐needle aspiration (FNA) is a minimally invasive and effective modality to diagnose pancreatic ductal adenocarcinoma. However, some histologic subtypes of ductal adenocarcinoma are rarely encountered and challenging to diagnose on FNA/small biopsies. To date, cytohistologic features of pancreatic sarcomatoid undifferentiated carcinoma with heterologous elements have not been thoroughly described. An 83‐year‐old man with lower back pain was found to have an incidental pancreatic neck mass. FNA biopsy of the mass showed rare markedly atypical, large, pleomorphic cells in a background of abundant calcifications/bone formation without areas of conventional adenocarcinoma. A diagnosis of “Malignant neoplasm with osteosarcomatous differentiation” was rendered on the FNA specimen. Subsequently, a Whipple resection revealed a 4.1 cm lobulated, calcified pancreatic mass. Microscopic examination showed a heavily calcified/ossified mass with adjacent areas of a highly cellular malignant spindle cell proliferation and admixed large, pleomorphic tumor cells; no background conventional adenocarcinoma was identified. Cytokeratin immunostains MNF116 and CK19 were positive in a large subset of the malignant spindle cells, and AE1.3/CAM5.2 showed patchy weak staining. Molecular testing revealed mutations in KRAS, TP53, BRCA2, NTRK3, EPHA2, MYD88, and CBL. No reportable fusions were detected. The final diagnosis was “Sarcomatoid undifferentiated carcinoma with heterologous elements (osteosarcomatous differentiation).” Definitive diagnosis of extremely rare subtypes of ductal adenocarcinoma is challenging on FNA biopsies. In this case, cytologic evaluation was helpful in making an early diagnosis of a malignant neoplasm with highly unusual features, prompting appropriate triage and early surgical resection of a sarcomatoid undifferentiated carcinoma with prominent osteosarcomatous differentiation.

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Section: Discussion/conclusionmentioning

confidence: 94%

Cytologic, histologic, and molecular features of pancreatic sarcomatoid undifferentiated carcinoma with heterologous osteosarcomatous transformation

Zhang

Sabatino

Castillo

et al. 2023

Diagnostic Cytopathology

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“…Undifferentiated carcinoma often shows partial glandular/ tubular formation, whereas HG-SPN lacks it. Mutations in KRAS, CDKN2A, and/or SMAD4 (DPC4) are frequently observed in undifferentiated carcinomas [21][22][23] but not in HG-SPNs. Poorly differentiated acinar cell carcinoma shows acinar differentiation confirmed by immunohistochemical expression of bcl-10 and/or trypsin, contrary to HG-SPN.…”

Section: Discussionmentioning

confidence: 99%

High-grade Solid Pseudopapillary Neoplasms of the Pancreas

Honda,

Yamaguchi,

Aimono

et al. 2024

American Journal of Surgical Pathology

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Pancreatic solid pseudopapillary neoplasm (SPN) is a low-grade malignant neoplasm with a good prognosis. Clinically aggressive SPNs have rarely been reported but have not been analyzed in detail. In this study, we referred to this highly malignant type of SPN as high-grade SPN (HG-SPN) and compared its clinicopathological and genetic characteristics with conventional SPN (C-SPN) using immunohistochemistry and gene panel analyses. Five HG-SPNs and 15 C-SPNs were evaluated in this study. HG-SPNs share many pathologic characteristics: macroscopically, solid/cystic appearances, microscopically, pseudopapillary/pseudorosette pattern (100%), tumor cell loose cohesiveness (100%), thin/delicate vasculature (100%), tumor cell cytoplasmic vacuolization (100%), immunohistochemical positivity for β-catenin (nuclear expression) (100%), CD10 (80%), CD56 (80%), and vimentin (100%). Conversely, HG-SPNs showed distinct malignant features compared with C-SPNs: mean tumor size (11.7 vs. 2.9 cm, P<0.001); true necrosis (100% vs. 0%, P<0.001); high-grade nuclear atypia (100% vs. 0%, P<0.001); lymphatic and/or venous invasion (100% vs. 20%, P=0.004); mean mitotic count (4.38 vs. 0.05/high-power field, P<0.001); and mean Ki-67 labeling index (33.9% vs. 3.4%, P<0.001). All HG-SPN patients died of primary disease 3 to 36 months after surgery, while all C-SPN patients were alive without disease. Genetic studies have shown that all analyzed HG-SPNs have CTNNB1 mutations. Two HG-SPN cases showed RB1 mutations with altered immunohistochemical findings for RB1 and p16. Two HG-SPN cases had TP53 mutation and/or p53 overexpression. In conclusion, HG-SPNs show distinct malignant features and some genetic alterations that differ from C-SPNs, indicating the importance of differentiating between these 2 subtypes.

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“…Genetic variations in undifferentiated pancreatic carcinoma have some commonalities with PDAC. There are frequent alterations in KRAS, TP53 and CDKN2A [ 3 , 9 , 14 , 22 , 23 ]. KRAS mutations may be absent in some cases, especially in the rhabdoid subtype [ 30 , 33 , 36 ].…”

Section: Molecular Characteristicsmentioning

confidence: 99%

“…The presence of a KRAS mutation is a hallmark of poor prognosis. Homozygous deletions of CDKN2A and CDKN2B have been reported, and so have SMAD4 mutations [ 3 , 22 ]. Rhabdoid carcinoma is marked by a lack of INI1 expression [ 33 , 34 , 36 ].…”

Section: Molecular Characteristicsmentioning

confidence: 99%

“…These tumors have three histological classifications: pleomorphic, osteoclastic and mixed-type [ 5 , 6 ]. In the literature, they are mostly reported as undifferentiated carcinomas with osteoclast-like giant cells (UCOGC) [ 3 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 ], giant cell pancreatic carcinoma [ 20 ], sarcomatoid carcinoma of the pancreas [ 21 , 22 ], or rhabdoid pancreatic carcinomas [ 23 , 24 , 25 ]. However, the histogenesis of these carcinomas remains controversial.…”

Section: Introductionmentioning

confidence: 99%

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Undifferentiated Pancreatic Carcinomas, Clinical Features and Therapeutic Options: What We Know

Mugaanyi

Huang

et al. 2022

Cancers

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Undifferentiated pancreatic carcinomas are rare malignant tumors of the pancreas that are very aggressive and challenging to diagnose. The WHO categorizes them into undifferentiated osteoclast-like giant cell, sarcomatoid, and rhabdoid pancreatic carcinomas. Patients present with nonspecific symptoms such as jaundice, vague abdominal or back pain and itchy skin. Their histological characteristics include positive pan-cytokeratin mononuclear pleomorphic cells, osteoclast-like giant cells and CD68. Patients may have KRAS, TP53 and SMAD4 alterations, homozygous deletions of CDKN2A and CDKN2B, as well as INI1 deficiency. Surgical resection is the only curative treatment. Patients may benefit from postoperative adjuvant therapy. There are no widely accepted guidelines specific to this type of tumor; however, some chemotherapy regimens may be promising. The patient prognosis is mostly poor, especially in patients with unresectable tumors. However, several studies have shown patients achieving long-term survival with adjuvant therapy. In conclusion, although undifferentiated pancreatic carcinoma is rare and very aggressive, there is still potential for improved patient survival with proper diagnosis and treatment.

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Genomic characterization of undifferentiated sarcomatoid carcinoma of the pancreas

Cited by 9 publications

References 32 publications

Cytologic, histologic, and molecular features of pancreatic sarcomatoid undifferentiated carcinoma with heterologous osteosarcomatous transformation

Cytologic, histologic, and molecular features of pancreatic sarcomatoid undifferentiated carcinoma with heterologous osteosarcomatous transformation

High-grade Solid Pseudopapillary Neoplasms of the Pancreas

Undifferentiated Pancreatic Carcinomas, Clinical Features and Therapeutic Options: What We Know

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