Serous cystic neoplasms

• Serous Cystic Neoplasms are also known as microcystic adenoma or glycogen-rich cystadenoma
• Serous Cystic Neoplasms usually presents as a large multiloculated mass
• The individual cystic cavities are small and filled with a clear ("serous") fluid
• The spongy appearance of the cut surface looks similar to infantile polycystic kidney
• The gross appearance is macrocystic (either multilocular or unilocular) or, rarely, solid
• Most cases are solitary, with a few multicentric examples on record
• A central scar is present in nearly half of cases

Microscopic features

• Composed of multiple small cysts with varying amounts of fibrous stroma
• The cysts are lined by small, flat, or cuboidal cells containing abundant glycogen but only an insignificant amount of mucin
• The nuclei are small and round, and the cytoplasm is clear
• Small papillae may project into the cyst lumens
• The amount of stroma is variable, ranging from delicate and highly vascular to dense and hyalinized
• Exceptionally, the stroma of the tumor contains amyloid deposits
• The stroma may feature calcifications, hemosiderin, or cholesterol clefts
• Islets of Langerhans or acinar tissue may be present in the trabeculae
• Immunohistochemically, there is reactivity for EMA, low-molecular-weight and broad-spectrum keratins, alpha-inhibin, MUC6, and calponin
• The fluid inside the cyst lumens has a low CEA level, unlike mucinous neoplasms

Additional Info

• Patients are usually elderly, and tumors are more common in women
• The disease is either discovered incidentally or manifests as an abdominal mass with local discomfort or pain
• Some cases occur with VHL disease and may harbor allelic deletions and mutations of the VHL tumor suppressor gene
• Serous cystic tumors have been seen in pancreata harboring ductal adenocarcinoma, neuroendocrine tumors (NETs), or IPMN elsewhere
• Diabetes may be associated with these lesions if sufficient islet cell tissue is destroyed by the tumor
• Tumors located in the head of the pancreas may result in gastrointestinal or biliary obstruction
• Excision is curative, though recent studies advocate for conservative management

Malignant Counterpart

• A malignant counterpart has been described as serous cystadenocarcinoma or microcystic adenocarcinoma
• The existence of a true malignant counterpart to serous cystadenomas remains controversial
• Cases previously designated as "malignant" or "invasive" serous neoplasms were either adherent to or invading local structures, sometimes with inflammation and hemorrhage
• These cases were neither cytologically malignant nor truly metastatic
• Some cases have reportedly exhibited nuclear atypia, perineurial invasion, and an aneuploid DNA pattern
• Aneuploidy has been found in morphologically unremarkable serous cystadenomas
• True adenocarcinomas may arise from serous cystic neoplasms ("carcinoma ex microcystic adenoma")

Mucinous Cystic Neoplasms

• MCN of the pancreas are seen in a younger age group (mean age at diagnosis is late 40s) compared to the Serous Cystic Neoplasms, and predominate in women
• Most are found the body and tail rather than in the head
• Clinical presentation is similar to microcystic adenomas and pancreatic pseudocysts

MCN Features

• Typically large (over 10 cm) multilocular or, in rare cases, unilocular cystic neoplasms with smooth internal surfaces that may contain papillary projections or mural nodules
• Cysts are lined by tall, mucin-producing columnar cells
• The underlying stroma is often very cellular, its appearance closely resembling that of ovarian stroma; the presence of ovarian-type stroma is a diagnostic criterion for this type of tumor
• Stroma is reactive for estrogen and progesterone receptors and for inhibin
• Stroma with these qualities can be seen in neoplasms developing in male patients
• Degenerative changes such as hemorrhage, hemosiderin, cholesterol clefts, and calcification are common, as is sloughing of the epithelial lining
• Aspiration of the cyst fluid can be useful in the differential diagnosis; the fluid contains higher levels of CEA than nonmucinous cysts
• MCN cannot communicate with the pancreatic ducts
• MCN must be distinguished from intraductal papillary mucinous tumors (see later), some of which may exhibit a cyst-like fusiform dilation of the involved ducts

Epithelial Atypia

• There is a range of it in MCN, ranging from bland, tall columnar mucinous epithelium with small, basally located nuclei to complex architecture with cribriforming, papillary formation, increased mitoses, and marked nuclear atypia
• It is common to see a wide range of architectural and cytologic atypia within a single neoplasm
• Previous classification schemes have divided MCN into mucinous cystadenomas, borderline MCN, and mucinous cystadenocarcinomas
• Newer classification schemes use a two-tiered scheme (low grade/ borderline vs. high grade/carcinoma in situ) so that greater uniformity of diagnosis and alignment with management considerations may be achieved

Invasive Adenocarcinoma

• When present, a variety of patterns may be seen, including ductal adenocarcinoma, adenosquamous carcinoma, mucinous adenocarcinoma, and undifferentiated carcinoma
• Invasive foci may be very small, and thus most authorities recommend entirely submitting these neoplasms following complete resection
• A morphologic variation on the theme of pancreatic MCN is represented by the occasional finding of a mural nodule with the features of a giant cell tumor, a pleomorphic sarcoma, or an anaplastic carcinoma
• The nature of these various types of proliferation is debatable, but all of them are regarded them as neoplastic and of epithelial nature

Further points on MCN

• MCN without associated invasive adenocarcinoma tend to follow a benign course
• Noninvasive MCN have an excellent prognosis, however, tumors with invasive components may have an aggressive clinical course with a 5-year survival rate of approximately 26%
• Metastases of MCN to the ovary may simulate a primary mucinous tumor of this organ
• The cells of MCN express EMA, SOX9, and cytokeratins 7, 8, 18, and 19, as well as CK10 and CK20 in many cases; MUC5AC and MUC6 expression is common
• MUC1 and MUC2 expression is often restricted to goblet cells, and MUC1 may also be limited to invasive components within MCN
• Reports of abnormal p53 expression in MCN have been inconsistent, but expression appears to increase with grade of dysplasia
• The majority of MCN with a component of invasive adenocarcinoma express EGFR and Her2/neu; furthermore, the invasive component loses expression of the DPC4 protein

Serous Cystic Neoplasms (SCN)

• Immunohistochemistry:
  • EMA: Positive
  • Low-molecular-weight and broad-spectrum keratins: Positive
  • α-Inhibin: Positive
  • MUC6: Positive
  • Calponin: Positive
• Genetics:
  • VHL gene: Allelic deletions and mutations may be present, especially in cases associated with VHL disease

Mucinous Cystic Neoplasms (MCN)

• Immunohistochemistry:
  • EMA: Positive
  • SOX9: Positive
  • Cytokeratins 7, 8, 18, 19: Positive
  • CK10 and CK20: Positive in many cases
  • MUC5AC and MUC6: Common but not absolute
  • MUC1 and MUC2: Often restricted to goblet cells; MUC1 may also be limited to invasive components
  • Estrogen and Progesterone Receptors: Positive in the ovarian-type stroma
  • Inhibin: Positive in the ovarian-type stroma
  • p53: Inconsistent reports; expression appears to increase with grade of dysplasia
  • EGFR and Her2/neu: Expressed in the majority of MCNs with an invasive adenocarcinoma component
  • DPC4: Loss of expression in the invasive component
• Genetics:
  • The genetic changes in MCNs are not explicitly detailed, but it mentions that the stroma is of monoclonal origin.

Key Points:

• SCN is characterized by EMA, keratin, α-inhibin, MUC6, and calponin positivity, and VHL gene mutations may be present
• MCN expresses a broader range of cytokeratins (including CK10 and CK20), MUC5AC, and MUC6
  • The ovarian-type stroma is positive for estrogen and progesterone receptors and inhibin
  • EGFR and Her2/neu are often expressed in the invasive components, which also show a loss of DPC4 expression
  • p53 expression may correlate with dysplasia grade