Case Title: Are you telling me I have a second cancer!
Objectives
1) Identify rare pancreatic mass lesions
2) Differential diagnosis of pancreatic tumors with eosinophilic cells and minimal atypia
Clinical History
A 81-year-old female with a recent history of lung adenocarcinoma status post radiation and chemotherapy was admitted for weakness, dyspnea and dizziness. A CT scan of her lung showed new inflammatory changes, residual lung cancer with a great initial treatment response, but also suggested a new pancreatic tail lesion. A follow up dedicated pancreas CT scan showed heterogenous pancreatic tail mass, 2.2 x 2.4 cm and considering patient’s history of lung adenocarcinoma the differential diagnosis was a new primary pancreatic malignancy versus metastatic lung cancer. Subsequently a CT guided biopsy was performed at interventional radiology.
Gross Description
Six needle core biopsies fragments.
Macroscopic Description
Microscopic evaluation revealed sheets of mildly atypical cells with eosinophilic cytoplasm and rare intracellular inclusions surrounded by clusters of macrophages. Fragments of unremarkable pancreatic parenchyma are also seen. Atypical glands, mucin, mitotic figures, and desmoplastic stroma are not identified. Immunohistochemical staining was performed and shows all the lesion cells are negative for cytokeratin AE1/AE3 and strongly positive for CD68. A Von Kossa calcium stain was performed.
Pre-Test Figure Legends

Figure 1. H&E-stained photomicrograph from low power showing fragments of pancreas and lesional tissue.

Figure 2. H&E-stained photomicrograph of pancreatic tail tumor shows a population of eosinophilic cells abutting groups of macrophages and pancreatic parenchyma. Intracellular inclusions are denoted with an arrowhead.

Figure 3. Immunostain for cytokeratin AE1/AE3 shows no staining of the eosinophilic cells and associated macrophages.

Figure 4. Immunostain for CD68 shows positive staining in the eosinophilic cells and associated macrophages.

Figure 5. Von Kassa Calcium stain highlighting rounded, concentric, intracytoplasmic inclusions.
Please select your diagnosis in the poll, then see the answer and the discussion in the links below.
Click Here To See The Answer Answer: Malakoplakia
Click Here To See The Discussion Discussion Malakoplakia is a non-neoplastic lesion that can be mass forming that consists of eosinophilic histocytes with basophilic intracellular inclusions. Immunostaining for CD68 confirmed the lesion consists primarily of macrophages and is negative for neoplastic epithelial cells. Malakoplakia most commonly occurs in the urinary bladder but also arises rarely in a wide spectrum of organs, including the pancreas1. Prevalence increases with age, diabetes mellitus, and immunosuppression. The characteristic histiocytes of this lesion are named von Hansemann cells and contain rounded, concentric, cytoplasmic inclusions named Michaelis-Gutmann bodies (denoted by an arrowhead on Figure 1), which are thought to arise from calcification of intracellular bacteria that have not been cleared by the immune system. Antibiotics are the mainstay of treatment and complete resolution is expected in nearly all cases. Well differentiated neuroendocrine tumors (WD-NET) of the pancreas can have many different histologic appearances and maybe appear to have rich eosinophilic cytoplasm and minimal atypia. Pancreatic neuroendocrine tumors are common, especially in the pancreatic tail and occasionally have dystrophic calcifications. Additionally, somatostatin producing neuroendocrine tumors can produce extracellular psammoma bodies that would stain with a Von Kossa calcium stain, but should not appear to be intracellular inclusions2. However, nearly all WD-NET should show immunostaining with a broad spectrum keratin, such as AE1/AE33. Acinar cell carcinoma are rare pancreatic carcinomas that differ in appearance to more common ductal adenocarcinomas as they typically are highly cellular and lack desmoplastic stroma4. Acinar cell carcinomas can appear as eosinophilic cells with intracellular granules mimicking the intracellular inclusions in this case, but these granules should not be highlighted by a calcium stain. Importantly, acinar cell carcinoma would be expected to be strongly keratin positive. Nuclear atypia may also be mild as in the lesional cells in this case. Metastatic melanoma can often appear as eosinophilic cells with absent keratin immunostaining, but often have more atypia, including binucleate cells and mitotic figures. Intracellular pigment can be present but should not be highlighted by a calcium stain. Lastly, immunostaining for CD68 would not be expected to stain melanoma cells. Metastatic lung adenocarcinoma should be highlighted by immunostaining for keratin and other markers of lung origin, such as TTF-1 and Napsin-A, and negative for CD68 staining. References: 1. Afzal RM, […], Phillips AE. Pancreatic Malakoplakia: A Rare Pathology Associated With Acute Pancreatitis. ACG Case Rep J. 2023. 2. Andrea Olivas, Tatjana Antic. The Presence of Psammoma Bodies in a Gastroentero-Pancreatic Neuroendocrine Tumor Should Raise the Suspicion for a Diagnosis of Somatostatinoma in Cytology Specimens, Journal of the American Society of Cytopathology, 2019. 3. Bellizzi AM. Immunohistochemistry in the diagnosis and classification of neuroendocrine neoplasms: what can brown do for you? Hum Pathol. 2020. 4. Kenji Ikezawa, […], Kazuyoshi Ohkawa, Comprehensive review of pancreatic acinar cell carcinoma: epidemiology, diagnosis, molecular features and treatment, Japanese Journal of Clinical Oncology, 2024. Case contributed by: Kurt W. Fisher MD/PhD
University of Nebraska Medical Center, Omaha Nebraska
Contact: kfisher@unmc.edu
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