Pathways Case Studies: November 2020

November 2020 — Hematopathology

A 50-year-old man was found to have multiple polyps on screening colonoscopy. Photomicrographs from a representative polypectomy specimen are shown below, with accompanying immunohistochemical panel.

Figure 1: H&E low power
Figure 2: H&E high power
Figure 3: IHC panel (Click on image to view larger)

What is the diagnosis?

  • Diffuse large B-cell lymphoma
  • Mantle cell lymphoma, blastoid/pleomorphic variant
  • Mantle cell lymphoma, traditional type
  • Small lymphocytic lymphoma with prominent proliferation centers

The correct answer is...

The correct answer is mantle cell lymphoma, blastoid/pleomorphic variant (in the setting of lymphomatous polyposis of the colon).

The photomicrographs show portions of polypoid colonic mucosa and submucosa with a diffuse infiltrate of small- to intermediate-sized CD20-positive B-cells with irregular nuclear contours, blast-like chromatin, occastional prominent nucleoli, and scant cytoplasm which expand the lamina propria and distort the colonic architecture. Immunohistochemically, the neoplastic B-cells show aberrant expression of CD5, and nuclear overexpression of cyclin D1 and SOX11. The cyclin D1 overexpression is indicative of the traditional t(11;14) translocation involving CCND1 and IGH consistent with mantle cell lymphoma. The Ki-67 proliferation index, increased at 70%, fits with the increased mitotic rate seen on H&E and indicates a more aggressive neoplasm. Collectively, these features are diagnostic of an aggressive variant of mantle cell lymphoma, blastoid type.

Traditional mantle cell lymphoma can often be seen in the setting of lymphomatous polyposis of the colon in asymptomatic individuals and would show the same immunophenotype as our case. However this diagnosis is excluded based on the atypical blast-like/pleomorphic morphology.

Small lymphocytic lymphoma (SLL) is another CD5-positive B-cell neoplasm which rarely can involve the gut. However, SLL shows a specific immunophenotype and morphology which typically includes prominent pale proliferation centers and lack of cyclin D1 and SOX11 positivity.

While diffuse large B-cell lymphoma (DLBCL) can occasionally be positive for CD5, shows an increased Ki-67 proliferation index, and can involve the GI tract, the morphology, SOX11, and cyclin D1 positivity exclude this diagnosis. Using an endothelial cell nucleus or histiocyte nucleus as an internal “ruler,” we can see that the nuclei of the neoplastic B-cells are similar in size to these cells, which is helpful in excluding the large B-cells seen in DLBCL.


References
1. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri S, Stein H, Thiele JE (2017) WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. Revised 4th edn. IARC, Lyon

Photo of Daniel (Dan) Larson, M.D. Daniel (Dan) Larson, M.D..
Fellow, Hematopathology
Mayo Clinic
Photo of Rebecca King, M.D. Rebecca King, M.D.
Consultant, Hematopathology
Mayo Clinic
Associate Professor of Laboratory Medicine and Pathology
Mayo Clinic College of Medicine and Science

November 2020 — Forensic & Neuropathology

60 year-old man with past medical history of coronary artery disease and smoking who was found unresponsive, slumped over in the bathroom of his residence. Toxicology report is unremarkable. These were the findings upon autopsy.

What should the manner of death be classified as?

  • Homicide
  • Natural
  • Undetermined
  • Accident

The correct answer is...

The correct answer is natural.

This case demonstrates the classical pattern of subarachnoid hemorrhage seen with a saccular aneurysm rupture. When looking at the base of the brain picture, an aneurysm is visible around the anterior communicating artery.

Subarachnoid hemorrhages (SAH) may arise from many etiologies, both traumatic and natural, and are simultaneously the most common indicator of traumatic brain injury and the classic presentation of a number of natural neurological vascular diseases. Accurate forensic evaluation of these findings should include assessment of scene along with autopsy findings.

Non-traumatic subarachnoid hemorrhages are most commonly associated with ruptured saccular aneurysms, which account for 80% of cases. A differential diagnosis should include arteriovenous malformations, cavernous angiomas mycotic aneurysms, neoplasm, blood dyscrasias and central venous thrombosis. In aneurysm rupture cases, the subarachnoid hemorrhage is typically limited or most predominantly focused near the base of the brain, posterior fossa, and the circle of Willis.

Most saccular aneurysms occur near the anterior portion of the circle of Willis with 38% being located along the anterior communicating artery. Search for a ruptured aneurysm should be conducted while the brain is in the unfixed state as formalin fixation with lead to hardening of the subarachnoid hemorrhage making it challenging to evaluate the vessels wound the Circle of willis.

Usually, ruptured aneurysms will bleed directly into the subarachnoid space, but occasionally, as seen in this case, a jet of blood from the strong arterial bleed can dissect through the brain parenchyma and reach the ventricular system, leading to concurrent intraventricular hemorrhages (in 63% of cases). These cases will result in sudden death in up to 60% of the time, usually unwitnessed and during sleep.

Traumatic subarachnoid hemorrhages will generally also be present over the convexity of the brain, extending along the Sylvian Fissures, and are usually seen in addition to contusions and lacerations along the brain parenchyma. Another etiology to consider when ruling out traumatic causes of subarachnoid hemorrhages is vertebral artery dissections, which are seen with severe hyperextension injuries of the head and neck. Common mechanisms include blows to the head or severe twisting of the neck. On gross exam, these cases show subarachnoid hemorrhages more centralized around the posterior cranial fossa, with tears in the ventral aspect of the brainstem being common.

After review of autopsy and scene findings on this case, cause of death is most consistent with a non-traumatic subarachnoid hemorrhage due to ruptured saccular aneurysm, and manner of death is determined to be natural (due solely to disease and aging process).

There are no findings that indicate a manner of death consistent with accident (an injury or poisoning resulting in an unintentional fatal outcome), suicide (self-infected injury with intent of self-harm) or homicide (injury by volitional act of another person with intent to cause harm). Classification of manner of death as undetermined, should only be used when information pointing to one manner of death is no more compelling than one or more other competing manners of death, which is not the applicable in this case.


References
1. Dolinak D, Matshes E, Lew E. Forensic Pathology. Amsterdam: Elsevier/Academic Press; 2012.
2. Ross J, Sandberg G, Powell S. Forensic Evaluation of Subarachnoid Hemorrhage. Acad Forensic Pathol. 2012;2(1):30-35. doi:10.23907/2012.004.
3. Troncoso J, Rubio A, Fowler D. Essential Forensic Neuropathology. Philadelphia: Wolters Kluwer Health; 2015.
4. Black M, Graham D. Sudden unexplained death in adults caused by intracranial pathology. J Clin Pathol. 2002;55(1):44-50. doi:10.1136/jcp.55.1.44.

Photo of Daniel (Dan) Larson, M.D. Fabiola Righi, D.O.
Resident, Anatomic and Clinical Pathology
Mayo Clinic
Photo of Peter Lin, M.D. Peter Lin, M.D.
Consultant, Anatomic Pathology
Mayo Clinic
Assistant Professor of Laboratory Medicine and Pathology
Mayo Clinic College of Medicine and Science

November 2020 — Cytopathology

An 80 year old woman underwent PET/CT imaging to assess for a pacemaker site infection and was found to have a 1.2 cm mass in the tail of the pancreas. An endoscopic ultrasound was performed with fine needle aspiration and cell block preparation.

Figure 1. Diff-Quick-stained smear, 200x
Figure 2. Pap-stained smear, 400x
Figure 3. H&E-stained cell block, 400x
Figure 4. Beta-catenin, 400x

What is the diagnosis?

  • Acinic cell carcinoma
  • Neuroendocrine tumor
  • Solid pseudopapillary neoplasm
  • Normal acinar cells

The correct answer is...

The correct answer is solid pseudopapillary neoplasm.

The diagnosis is solid pseudopapillary neoplasm (SPN) of the pancreas. SPN are rare, accounting for 1-2% of pancreatic exocrine neoplasms. They predominately occur in young women but can also be detected in men and older adults. They are found in any location within the pancreas, with a slight predilection for the tail. SPN are frequently identified incidentally by imaging or may present with abdominal pain. Characteristic imaging findings include a well circumscribed mass with variably solid and cystic components. Fine needle aspirates (FNA) are generally moderately to highly cellular and composed of single cells, loosely cohesive groups, and tissue fragments (Figure 1) with layers of cells loosely arranged around a central fibrovascular core (Figure 2). The cells are monomorphic with a variable amount of cytoplasm, which may contain vacuoles, hyaline globules, or cytoplasmic tails. The nuclei are eccentrically located, round to ovoid, and exhibit fine chromatin with grooves and small nucleoli (Figure 2). Extracellular globules of metachromatic material (Figure 1, arrows), foamy histiocytes, and necrotic debris may also be present in the background. The pseudopapillae are highlighted on histologic sections (Figure 3) and contain broad hyalinized or myxoid fibrovascular cores with loosely clinging tumor cells. Immunohistochemically, the tumor cells show nuclear expression of beta-catenin (Figure 4) and may be focally reactive for pan-keratin and synaptophysin.

The cytological differential diagnosis for SPN includes normal pancreatic acinar cells, acinic cell carcinoma (ACC), and neuroendocrine tumor (NET). Normal pancreatic acini are composed of grape-like clusters of cohesive cells, with abundant finely granular cytoplasm and eccentrically located nuclei with small nucleoli, and may surround fibrovascular tissue. Recognition of single cells and fine fibrovascular cores with loosely attached layers of tumor cells with a monomorphic appearance as well as the presence of intracytoplasmic hyaline globules and extracellular matrix material should aid in the distinction. FNA from acinic cell carcinoma demonstrate isolated cells and loose aggregates of uniform cells with granular cytoplasm and round to ovoid nuclei with smooth contours, and unlike SPN, typically contain prominent nucleoli and show some degree of nuclear atypia. Diffuse immunoreactivity for pan-keratin and trypsin distinguish ACC from SPN. ACC may also show focal reactivity for neuroendocrine markers, and nuclear expression for beta-catenin is observed in approximately 10%. FNA from neuroendocrine tumors demonstrate isolated and small clusters of plasmacytoid cells with uniform round to ovoid nuclei and characteristic finely stippled (“salt and pepper”) chromatin. Prominent nucleoli and delicate capillaries may also be observed. In addition to the characteristic nuclear appearance, immunoreactivity for pan-keratin, synaptophysin, and chromogranin as well as non-nuclear expression of beta-catenin helps distinguish NET from SPN.

SPN is considered a tumor of low malignant potential and has an excellent prognosis after surgical resection. Approximately 10-15% locally recur or metastasize.


References
1. Cibas ES, Ducatman BS. Cytology: Diagnostic Principles and Clinical Correlates. Elsevier; 2020.
2. Mody DR, Thrall MJ, Krishnamurthy S. Diagnostic Pathology: Cytopathology. Amirsys; 2018.
3. Arends MJ, Fukayama M, Klimstra DS, et al., editors. WHO Classification of Digestive System Tumours. Lyon, France: IARC Press; 2019.
4. Hooper K, Tracht JM, Eldin-eltoum IA. Cytologic criteria to reduce error in EUS-FNA of solid pseudopapillary neoplasms of the pancreas. J Am Soc Cytopathol. 2017;6(6):228-235.

Photo of Amy Swanson, M.D. Amy Swanson, M.D.
Fellow, Cytopathology
Mayo Clinic
Photo of Michael Henry, M.D. Michael Henry, M.D.
Consultant, Anatomic Pathology
Mayo Clinic
Professor of Laboratory Medicine and Pathology
Mayo Clinic College of Medicine and Science
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