Undifferentiated Carcinoma With Osteoclast-like Giant Cells of the Pancreas Diagnosed by EUS-Guided Fine-Needle Biopsy

Abstract

Undifferentiated carcinoma with osteoclast-like giant cells of the pancreas is an extremely rare malignancy with nonspecific radiological features, often requiring histological confirmation. We report the case of a 57-year-old woman presenting with abdominal pain and cholestasis, in whom imaging revealed a pancreatic head mass. After an initial nondiagnostic endoscopic ultrasound sampling, endoscopic ultrasound–guided fine-needle biopsy performed at our tertiary referral center allowed definitive diagnosis by identifying characteristic osteoclast-like giant cells and undifferentiated neoplastic cells with a specific immunohistochemical profile. This case highlights the key role of endoscopic ultrasound–guided fine-needle biopsy in the preoperative diagnosis of undifferentiated carcinoma with osteoclast-like giant cells.

INTRODUCTION

Undifferentiated carcinoma (UC) of the pancreas is a rare but aggressive subtype of pancreatic cancer. Over the past years, anaplastic, pleomorphic, spindle cell, sarcomatoid carcinoma, and carcinosarcoma have been used as an alternative for UC. In the current World Health Organization classification, the pancreatic UC and the UC with osteoclast-like giant cells (UC-OGC) are considered 2 different entities for their histological and clinical differences.¹

UC-OGC is extremely rare, accounting for <1% of pancreatic cancers, and was first reported by Sommers and Meissner in 1954.² Diagnosis is challenging because of the absence of specific radiological features. UC-OGC is generally larger than pancreatic ductal adenocarcinoma and presents a cystic component.³ The magnetic resonance imaging appearance of UC-OGC provides a well-defined, hypovascular, and low-intensity lesion on T2-weighted imaging.⁴ However, the radiological assessment is generally not enough for a definitive diagnosis, and a cytological or histological examination is frequently required. Few reports describe endoscopic ultrasound (EUS)–guided sampling of UC-OGC.^5,6 We report a case of UC-OGC diagnosed by EUS-guided fine-needle biopsy.

CASE REPORT

A 57-year-old woman with a remote smoking history presented with acute abdominal pain. The clinical examination was normal, and the laboratory tests revealed increased cholestatic enzymes with normal blood tumor markers.

Transabdominal ultrasonography documented hepatic cystic lesions, without characterization of the pancreatic mass. Contrast-enhanced computed tomography (CT) demonstrated a 36 × 31 mm cystic lesion in the pancreatic head with internal septa and postcontrast enhancement, which infiltrated the splenoportal axis, causing upstream dilation of the Wirsung duct (5 mm) and common bile duct (10 mm) (Figure 1). Follow-up CT scans confirmed the presence of hepatic metastases, consistent with stage IV disease. Magnetic resonance imaging was not performed due to the patient's claustrophobia, thereby limiting further noninvasive imaging characterization of the lesion. Given insufficient noninvasive imaging for definitive diagnosis, EUS-FNB was performed. A 4.0 × 4.0 cm mixed solid-cystic lesion in the head of the pancreas was identified. Mild upstream dilation of the Wirsung was noted, consistent with ductal obstruction, and the adjacent venous mesentericoportal axis appeared to abut the lesion without a clearly identifiable plane of cleavage on the imaging study (Figure 2). The first sampling was nondiagnostic, showing no malignant cells and insufficient tissue for definitive histopathological assessment. A second EUS-FNB was repeated in a tertiary-level center. The procedure was performed using a 22-gauge Franseen-tip needle (Acquire, Boston Scientific), specifically targeting the solid component of the heterogeneous solid-cystic lesion. We used the fanning technique with wet suction, and 3 needle passes were performed to ensure adequate tissue acquisition. This approach, targeting the solid component with optimized acquisition techniques, yielded sufficient histological core tissue for definitive diagnosis.

Figure 1.

Endoscopic ultrasound (EUS) image of the pancreatic head. The lesion measures approximately 5 cm and shows a heterogeneous solid-cystic appearance with hypoechoic solid areas and inner anechoic lacunae, characteristic of undifferentiated carcinoma with osteoclast-like giant cells (UC-OGC). Upstream common bile duct dilation and portal vein infiltration are also visible, highlighting mass effect and vascular involvement.

Figure 2.

Histology of the pancreatic lesion using hematoxylin and eosin stain, x200 magnification. The neoplasm is composed of three cell types: mononuclear neoplastic cells with marked atypia, mononuclear histiocytes (non-neoplastic), and multinucleated osteoclast-like giant cells (non-neoplastic). The presence of CD68-positive multinucleated giant cells and pleomorphic mononuclear neoplastic cells is a key diagnostic feature of UC-OGC.

The histological analysis revealed the presence of numerous osteoclast-like giant cells (OGCs) and undifferentiated cells exhibiting significant pleomorphism and nuclear atypia (Figure 3). Immunohistochemically, the undifferentiated neoplastic cells were stained for cytokeratins AE1/AE3 and CK19 (Figure 4). OGCs reacted strongly for CD68 (KP1 clone) and were negative for all other markers tested. Histology and immunohistochemistry were consistent with UC of the pancreas with osteoclast-like giant cells (UC-OGC).

Figure 3.

Immunohistochemistry of the pancreatic lesion (IHC stain, x200 magnification). Neoplastic cells show focal positivity for PANCK, while non-neoplastic multinucleated giant cells are strongly positive for CD68 (KP1 clone). This pattern confirms the presence of undifferentiated carcinoma with osteoclast-like giant cells.

Figure 4.

Contrast-enhanced CT shows a 36x31 mm cystic lesion in the pancreatic head with enhancing septa, infiltrating the splenoportal axis and causing dilatation of the pancreatic and common bile ducts.

No endoscopic retrograde cholangiopancreatography was performed due to the absence of cholangitis or obstructive jaundice. The common bile duct was dilated (max 23 mm) and was managed conservatively. Follow-up CT confirmed progression of the pancreatic lesion (up to 58 × 48 mm). Given these findings, pancreatic resection was not performed. First-line chemotherapy with gemcitabine and nab-paclitaxel was initiated, followed by FOLFIRINOX and radiotherapy due to disease progression. During follow-up, in addition to periodic imaging assessments, serial laboratory evaluations were performed. Laboratory tests demonstrated elevated CA19-9 and cholestatic enzymes before chemotherapy, with improvement during treatment. The multimodal approach led to a reduction in pancreatic mass (56 × 48 mm vs 61 × 56 mm) with stable hepatic disease. The patient has maintained disease control for over 30 months since diagnosis and remains under active surveillance.

DISCUSSION

According to the 2019 World Health Organization classification, UC-OGC is a histological subtype of pancreatic ductal adenocarcinoma (PDAC).⁷ It affects patients in the sixth to seventh decades, with a slight female predominance (male:female, 9:10). Symptoms are nonspecific, including abdominal pain, abdominal discomfort, back pain, anorexia, and weight loss. Jaundice and anemia have been reported occasionally.⁸ UC-OGC typically shows infiltrative nodular growth, is mostly located in the head of the pancreas (about 60% of cases),⁹ and causes dilation of both the main pancreatic duct and common bile duct.^8,9 Despite the large volume, lymph node metastases are rarely observed.⁹ Distant metastases may occur in advanced stages and are most common in the liver, lung, and bone. On CT, UC-OGC appears as a heterogeneous mass with solid and cystic components, reflecting hemorrhagic and necrotic changes.¹⁰ However, these radiological findings are not pathognomonic and may overlap with other pancreatic neoplasms. Differential diagnosis includes cystic PDAC, intraductal papillary mucinous neoplasm (IPMN), mucinous cystic neoplasm, serous cystadenoma, and solid pseudopapillary tumor, requiring histological confirmation. Histologically, UC-OGC is characterized by CD68-positive osteoclast-like giant cells admixed with CK/CK19-positive undifferentiated neoplastic cells, often associated with hemorrhagic necrosis and hemosiderin deposits. Pathological confirmation is usually obtained from surgical specimens. Chadha et al¹¹ reported diagnostic yield from biopsy specimens from laparotomy or liver metastases. However, a less invasive approach is demanded for the preoperative diagnosis of pancreatic UC.

EUS is particularly valuable for diagnosing UC-OGC, allowing targeted sampling of the solid component in heterogeneous lesions. The use of Franseen-tip needles with fanning technique and multiple passes improves diagnostic yield in cystic-solid tumors.¹²

Reported cases of UC-OGC show marked clinical heterogeneity. Early-stage disease may be treated surgically, whereas advanced cases require multimodal therapy, including chemotherapy and/or radiotherapy, with variable outcomes.^13,14

Different prognostic patterns have been described in UC-OGC, with longer survival reported in pure forms than in tumors associated with conventional PDAC components. In particular, Luchini et al¹⁵ reported a median overall survival of 36 months for pure UC-OGC vs 15 months for UC-OGC associated with PDAC. In this context, obtaining a pretreatment diagnosis by EUS-FNB allowed histological characterization before therapy and guided a multimodal treatment approach, avoiding nonbeneficial surgery in the presence of metastatic disease. This case highlights the value of EUS-FNB in preoperative diagnosis of metastatic UC-OGC, avoiding nontherapeutic surgery in unresectable disease.

DISCLOSURES

Author contributions: MF Chiappetta conceived and designed the work, collected and interpreted the data, and drafted the manuscript. M. Murgiano reviewed and revised the manuscript. FB de Andreis, C. Ciuffini, LG Papparella, SF Vadalà di Prampero, and M. Fiorani contributed to data acquisition and interpretation and critically revised the manuscript. G. Costamagna and M. Bulajic contributed critically revised the manuscript. All authors approved the final version of the manuscript and agree to be accountable for all aspects of the work. MF Chiappetta is the article guarantor.

Financial disclosure: None to report.

Informed consent was obtained for this case report.

ABBREVIATIONS:

CA19-9

carbohydrate antigen 19-9

CD68

cluster of differentiation 68

CK

cytokeratin

CT

computed tomography

ERCP

endoscopic retrograde cholangiopancreatography

EUS

endoscopic ultrasound

EUS-FNB

endoscopic ultrasound-guided fine needle biopsy

FNB

fine needle biopsy

IPMN

intraductal papillary mucinous neoplasm

MRI

magnetic resonance imaging

OGCs

osteoclast-like giant cells

PDAC

pancreatic ductal adenocarcinoma

UC

undifferentiated carcinoma

UC-OGC

undifferentiated carcinoma with osteoclast-like giant cells

WHO

World Health Organization