Case of the Month: Cytopathology

April 2016 Case of the Month authored by Cytopathology Fellow Katherine Phillips, M.D.

Clinical History

A 10-year-old female with no significant past medical history presented with a several-day history of abdominal pain, nausea and vomiting. Lipase was elevated at 243. Abdominal ultrasound revealed a 2.8 cm, round, solid-appearing pancreatic head mass. Magnetic resonance cholangiopancreatography (MRCP) confirmed the pancreatic head mass, which demonstrated heterogeneous internal signal, suggestive of hemorrhagic internal contents. The patient subsequently underwent endoscopic ultrasound with a fine-needle aspiration (FNA) biopsy of the lesion.

Pathologic Findings

Direct smears were prepared, revealing a cellular sample of monomorphic, cuboidal tumor cells arranged in loosely cohesive groups and single cells that were aligned along vascular structures (Figure 1).

Figure 1: Diff-Quik stain; 20X; loosely cohesive, cuboidal cells arranged around fibrovascular cores

The tumor cells had delicate-to-granular cytoplasm, indistinct cell borders and round-to-oval nuclei, with finely dispersed chromatin and occasional nuclear grooves (Figure 2).

Figure 2: Pap stain; 40X. Loosely cohesive, isolated tumor cells fill the background. These cells are monomorphic, with delicate cytoplasm and round-to-oval nuclei.

A cell block was prepared, which revealed discohesive single tumor cells with cellular morphology--similar to that seen on the direct smears.

Immunohistochemical Studies

Immunohistochemical studies were performed on the cell block. The tumor cells were immunoreactive with cytokeratin AE1/3, CD10, and CD56, with nuclear β-catenin (Figure 3) and cytoplasmic granules stained for alpha-1 antitrypsin.

Figure 3: β-catenin immunohistochemistry, 40X, highlighting nuclear reactivity

The tumor cells were non-reactive with trypsin, chymotrypsin, synaptophysin and chromogranin.

 



Diagnosis

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Discussion

Solid pseudopapillary neoplasm is an uncommon tumor comprising one to two percent of pancreatic neoplasms. This tumor occurs almost exclusively in young women (90 percent), with a mean age of 28 years. Symptoms may include abdominal pain, early satiety, and nausea/vomiting with many found incidentally on imaging.

Grossly, these tumors are well-circumscribed lesions with variable amounts of solid and cystic areas. They can occur at any location within the pancreas and are typically large at diagnosis (mean: 9 - 10 cm in diameter).

Histologically, these tumors are characterized by solid, cystic, and pseudopapillary morphology. The pseudopapillae arise secondary to poor cohesion of tumor cells around fibrovascular stalks. The tumor cells are monomorphic, with occasional bean-shaped nuclei, nuclear grooves and pale-to-granular cytoplasm. Cytoplasmic vacuoles may also be present, as well as PAS-positive, diastase-resistant hyaline globules. Mitoses are rare. Foamy macrophages, calcifications and cholesterol granulomas can form in areas of cystic degeneration.

Cytologically, these tumors yield cellular smears composed of monomorphic cuboidal cells, arranged in loose clusters. Pseudopapillae are seen as fibrovascular cores with myxoid stroma, surrounded by poorly cohesive cells. This myxoid stroma is highlighted best on Romanowsky stain as magenta-colored metachromatic material. Isolated tumor cells fill the background, which may be clean or filled with hemorrhagic cyst debris. The tumor cells are homogeneous, with delicate cytoplasm and round-to-oval nuclei, as well as with fine chromatin, occasional nuclear grooves and indistinct nucleoli. Cytoplasmic vacuoles and hyaline globules may also be seen.

The immunohistochemical staining pattern is distinctive and a result of its molecular alterations. β-catenin (CTNNB1) mutations lead to constitutive activation of the Wnt pathway. Alteration in the Wnt/β-catenin pathway leads to nuclear accumulation of the protein in greater than 95 percent of tumors. Positive nuclear staining with β-catenin is the key diagnostic feature of solid pseudopapillary neoplasm.

Solid pseudopapillary neoplasms are considered tumors of low malignant potential. Most are treated successfully with surgical resection and have a five-year survival rate of greater than 95 percent. Approximately 10 percent of these tumors demonstrate more aggressive behavior with recurrence and metastasis. Histologic features that may be associated with aggressive behavior include perineural invasion, vascular invasion and invasion of adjacent structures, although tumors lacking these features have been found to metastasize.

References

  1. Jahangirl, Sidra et al. "Accuracy of Diagnosis of Solid Pseudopapillary Tumor of the Pancreas on Fine Needle Aspiration: A Multi-Institution Experience of Ten Cases." CytoJournal 2015; 12:29.
  2. Terris, Benoit, and Cavard, Cathereine. "Diagnosis and Molecular Aspects of Solid-Pseudopapillary Neoplasms of the Pancreas." Seminars in Diagnostic Pathology 31 (2014) 484-490.
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