SOLID-PSEUDOPAPILLARY NEOPLASM OF PANCREAS

SOLID-PSEUDOPAILLARY NEOPLASM OF PANCREAS

• It is a malignant epithelial tumor of low grade

• The name of this tumor is due to its gross and microscopic appearance

• Synonyms-Solid pseudo papillary tumor, papillary cystic neoplasm, papillary epithelial neoplasm, solid and papillary epithelial neoplasm, low grade papillary neoplasm, Hamoudi’s tumor, Frantz’s tumor

• General features 

  • Features of this tumor were first recognized in 1959 by Frantz.

  • Incidence of this tumor is 0.9 to 2.7% of the pancreatic malignancies

  • They constitute 6% of all exocrine pancreatic neoplasms

  • Sex – more common in women

  • Age-occurs in younger age group  with mean at presentation being 28 years (7 to 79 years).In men they occur 5 to 10 years older than women.

• Clinical features

  • Present with nonspecific symptoms like abdominal pain, intraabdominal mass, nausea, vomiting and dyspepsia

  • These tumors are discovered incidentally on physical examination

  • Some of them may rapture producing hemoperitoneum

  • Rarely patient may develop jaundice.

• On imaging these tumors present as well circumscribed neoplasm with solid and cystic component calcifications are seen in 30% of cases, CT scan and ultrasound shows well demarcated heterogenous mass.

• Angiography typically shows splaying and draping of the vessels and mild vascularity in some areas.

• On MRI solid areas have signal intensity similar to liver on T1 weighted masses, where as fluid areas appear hypotense and hemorrhagic areas are hyper intense.

Morphology:

• Gross:

  • These tumors are evenly distributed throughout pancreas i.e, approximately 1/3^rd arise in tail, 1/3^rd in body and 1/3^rd in head

  • Rare sites of occurrence

    • Retroperitoneum behind the head of pancreas

    • Ectopic pancreas in colon

  • Mostly solitary but can present as multicentric neoplasm

  • Size-ranges from 0.5 to 25cms with mean diameter of 9 to10cm

  • Most are well circumscribed and appear encapsulated with calcifications in capsule

  • Cut section – cystic lesion with soft gray white to yellow solid areas. Cystic cavity contains friable necrotic material and hemorrhage. Some of these tumors can be completely solid and some may be completely cystic with thin rim of tumor at the periphery.

Microscopic findings:

• • Tumor is composed of relatively uniform polygonal cells admixed with delicate capillaries.

  • Pseudopapillae are formed when the neoplastic cells drop away, leaving variable numbers of loosely cohesive cells surrounding delicate capillary sized blood vessels.

  • In these areas, nuclei of the tumor cells are oriented away from vessels, which result in zone of cytoplasm that separates the capillaries from the nuclei.

  • Tumor cells have eosinophilic cytoplasm. Cytoplasmic vacuoles may be present. Some cells may have clear or foamy cytoplasm.

  • Nuclei of tumor cells are round to oval and uniform and have stippled chromatin and may show frequent longitudinal nuclear grooves.

  • Mitoses are rare (range 0-10/50 hpf)

  • Some tumor cells may have prominent intracytoplasmic eosinophilic hyaline globules that range in size from 1-20mm and are PAS positive diastase resistant.

  • Degenerative changes include

    • Foamy macrophages

    • Cholesterol crystals

    • Hemorrhage

  • Few tumors may show pigment which may be melanin or lipofusin.

  • Stroma surrounding the vessels may be hyalinised or myxoid. Few tumors may show balls of myxoid stroma within solid regions, producing cylindromatous pattern.

  • Calcifications and focal ossifications can also be present in capsule.

  • Though the tumor is well circumscribed tumor cells can be seen infiltrating into the adjacent pancreatic parenchyma.

  • “Blood lakes” will be present at the periphery of the tumor. RBC’s and tumor cells are intermingled giving the appearance of vascular invasion in the places.

  • Vascular and perineural invasion is noted in rare cases.

  • Areas of infarction can be seen but tumor necrosis is often absent.

Histologic types:

• Solid non encapsulated variant– It is small tumor which has not grown large to undergo cystic changes

• Diffusely infiltrative variant–

  • In this tumor cells are intimately associated with benign pancreatic acini

  • These tumors may undergo malignant transformation with high mitotic rate (35-69/50hpf), true tumor necrosis and nuclear pleomorphism. Sarcomatoid differentiation can also occur in these tumor.

Immunohistochemical findings:

• Tumor cells are strongly positive for

  • Vimentin

  • Alpha-1 antitrypsin

  • CD-10

  • Neuron specific enolase

  • Progesterone receptors

• They variable express

  • Synaptophysin

  • Cytokeratin (AE1/AE3, CAM5.2)

  • Cyclin D1

  • Intracytoplasmic hyaline globuling-positive for alpha – 1 antitrypsin.

• Tumor cells are negative for

  • Chromogranin

  • Insulin

  • Glucagon

  • Somatostatin

  • Lipase

  • Calretinin

  • Alpha inhibin

  • CD34

  • Placental alkaline phosphatase

  • EMA

  • CEA

  • S-100

  • Estrogen receptors

 

• Differential diagnosis:

• Pseudocyst of pancreas 

• • Resemble SPPN on imaging

  • Pseudocysts are common in men and patient has history of pancreatitis, raised serum amylase levels, chemical analysis of cyst fluid demonstrates high levels of amylase

  • Whereas SPPN is common in women, do not have associated pancreatitis and have normal serum and low cyst fluid amylase

  • Microscopically pseudocysts have no lining whereas SPPN has tumor cells at the periphery.

•  Well differentiated endocrine neoplasm

  • Though both tumors have uniform tumor cells, presence of pseudopapillae, foamy macrophages, cholesterol clefts and eosinophilic hyaline globules favours the diagnosis of SPPN

  • Pancreatic endocrine neoplasms are strongly positive for endocrine markers like Synaptophysin, Chromogranin and pancreatic hormones like insulin, glucagon and somatostatin whereas SPPN weakly express synaptophysin and are negative for chromogranin

  • Well differentiated pancreatic endocrine tumors have coarse speckled “salt and pepper chromatin” which is absent in SPPN.

• Spread and Metastasis: 

  • Capsular infiltration should not be taken as indicator of malignancy

  • Aggressive tumor may directly extend into the adjacent stomach, duodenum and spleen

  • Metastasis to liver or peritoneum may occur. Lymph node metastasis and metastasis to skin is rare

• Treatment 

  • Surgical resection is treatment of choice

  • Prognosis is excellent

References 

• Ralph H. Hruban, Martha Bishop Pitman, David S. Klimstra. Tumors of the Pancreas. AFIP Atlas of Tumor Pathology Series 4.