Dystrophic Adipocytes Mimicking Metastatic Signet Ring Cell Adenocarcinoma: A Diagnostic Pitfall in a Cachectic Patient

Abstract

Cachexia is a debilitating condition and complex syndrome commonly associated with a variety of chronic diseases. It is caused by metabolic dysregulation and characterized by profound loss of adipose tissue and skeletal muscles. While pathological changes of cachectic conditions on adipose tissue have been studied and documented in tumor-bearing animal models, similar morphological changes in human surgical specimens are rare. Here we report a case of a cachectic patient with pancreatic adenocarcinoma whose adipocytes underwent dramatic lipodystrophy mimicking signet ring cell adenocarcinoma. The patient had presented with a large bowel obstruction, a mass extending between the pancreas and colon, and radiographic concern for carcinomatosis. A moderately differentiated adenocarcinoma was identified invading externally into the colon, with extensive signet ring-like cells throughout the specimen, including those adjacent to the colon and lymph nodes and around nerves. These signet ring-like cells were round with variably clear to eosinophilic cytoplasm and a peripherally displaced round to oval nucleus. Immunohistochemical staining demonstrated that these signet ring-like cells were negative for AE1/AE3, CD138, or Kreyberg staining, while they were positive for S-100 staining, confirming these as dystrophic adipocytes. Here we examine dystrophic adipocytes in a cachetic patient, examining the differential diagnosis and potential ancillary studies.

Adipocyte Atrophy Mimicking Signet Ring Cell Carcinoma of the Gallbladder

“…In most cases, the cells of concern were identified as atrophic adipocytes which uniformly stain positively for S100 protein and variably for calretinin, but negatively for pancytokeratin markers, histiocyte markers, vascular markers, melanocyte markers, other mesothelial markers, and mucin [ 1 , 2 , 5 – 8 ]. The cells lack cytologic or nuclear atypia and generally retain their normal lobulated, circumscribed architecture, although occasional pseudoinfiltrative growth has been seen and the cells may also be seen within lymph nodes and around nerves [ 6 ]. They are smaller than typical adipocytes, with mild size variation and rounded, thickened peripheral membranes, and are usually univacuolated although occasional multivacuolation has been described [ 5 , 6 ].…”

“…The cells lack cytologic or nuclear atypia and generally retain their normal lobulated, circumscribed architecture, although occasional pseudoinfiltrative growth has been seen and the cells may also be seen within lymph nodes and around nerves [ 6 ]. They are smaller than typical adipocytes, with mild size variation and rounded, thickened peripheral membranes, and are usually univacuolated although occasional multivacuolation has been described [ 5 , 6 ]. The background stroma often shows conspicuous myxoid/mucoid change with a prominent delicate capillary network, and cells may show clustering around blood vessels [ 2 , 5 , 7 ]; this appearance has raised concern for myxoid liposarcoma [ 5 ].…”

“…The background stroma often shows conspicuous myxoid/mucoid change with a prominent delicate capillary network, and cells may show clustering around blood vessels [ 2 , 5 , 7 ]; this appearance has raised concern for myxoid liposarcoma [ 5 ]. Fibrosis may also be seen in association with the signet ring cells, which may accentuate lobulation [ 5 , 6 , 8 ].…”

“…In most cases, nonepithelial signet ring cell change has been associated with cachexia, with underlying causes including malignancy [ 5 , 6 , 8 ], mixed chronic inflammatory disease [ 7 ], and anorexia nervosa [ 5 ]. At admission, the BMI of these patients is reported to have ranged from 11.0 to 16.7 kg/m 2 .…”

“…It is possible that convergent morphologic alterations may be seen both in response to cachexia and severe inflammation. The finding is also associated with high mortality, with at least two of six reported antemortem cases culminating in death during hospital admission [ 2 , 5 ], likely related to the underlying medical condition and/or cachexia which is itself associated with increased mortality [ 6 ].…”