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Starvation-induced fat atrophy in the omentum: a diagnostic pitfall
INSTRUCTIVE CASE
Starvation-induced fat atrophy in the omentum: a diagnostic pitfall
had a right inguinal hernia since he was a teenager. In order to facilitate his rehabilitation, a repair of the hernia was undertaken. At operation, two hernias were identified: one direct and the other an indirect hernia. The hernia sac was opened and caecum, small bowel and appendix were identified. The hernia was reduced and the bowel contents returned into the abdomen. Since the indirect sac was large, a portion was resected and sent to Pathology. The hernia was repaired and the patient recovered uneventfully. In the course of acquiring more clinical information after the hernia sac was examined microscopically, it was ascertained that the patient had weight loss of over 100 lbs over a 5 month period as a result of the dysphagia and inability to eat.
Rajkumar Vajpeyi Runjan Chetty
Abstract The histological changes encountered in fat as a consequence of starvation are not often encountered in surgical pathology. We present two cases in which the changes in the fat were so striking that other conditions were considered. In both cases weight loss due to decreased intake (dysphagia with oesophageal cancer, and anorexia nervosa) resulted in marked atrophy of fat. The atrophic fatty tissue was noted in tissue sampled in a hernia repair and, in the second case, a hemicolectomy for pneumatosis intestinalis. The atrophic fat was characterized by small signet ring cells suspended in a mucoid/myxoid stroma that contained a very prominent delicate capillary network. This appearance raised suspicion for both signet cell carcinoma and myxoid liposarcoma. However, the lobular noninfiltrative pattern, relevant immunohistochemistry and appropriate clinical history, help reach the correct interpretation.
Case 2 The patient was a 26-year-old woman who reported involuntary weight loss of 50e60 lbs over a year. She was admitted to hospital for weakness and profound malnutrition. On examination, she was cachectic and weighed 70 lbs with a body mass index of 11 kg/m2. Routine laboratory results were in keeping with starvation, and included hypokalaemia (3.0 mmol/L), hypoalbuminaemia (27 g/L), and elevated serum aminotransferases (ALT 307 U/L and AST 274 U/L). There was no evidence of an organic cause for the patient’s severe weight loss. Investigations for diabetes, thyroid disease, malabsorption syndromes, malignancy, and toxicology were all negative. The patient was seen by the Psychiatry service, and was diagnosed with anorexia nervosa. An abdominal ultrasound performed on admission was normal but a CT scan demonstrated extensive intra- and extraperitoneal free air with pneumatosis of the ascending colon. In view of this, a right hemicolectomy was performed. Intraoperatively, there were no signs of perforation, peritonitis, bowel ischaemia/necrosis. A post-operative chest radiograph revealed multiple bilateral cavitary lesions with consolidation and bilateral pneumothoraces. The patient developed progressive respiratory failure and died 1 month after admission. A postmortem examination was not performed.
Keywords atrophy; capillary network; fat; signet ring-like cells; starvation
During periods of starvation or malnutrition, especially when prolonged, atrophy of tissue and organs is the rule. In most sites the actual morphological appearance of organs is not fundamentally altered. In other words, atrophic cardiac muscle, for instance, is still recognizable as cardiac muscle. However, severe atrophy of fatty tissue can alter the appearance of adipocytes to such an extent that it is not readily apparent as fat.1 Fat atrophy is most vividly seen in subcutaneous and omental fat. We present two cases in which there was extreme atrophy of omental fat resulting in morphologic mimicry of other fatty lesions and/or vascular lesions, and hence diagnostic concerns.
Clinical details Case 1 A 55-year-old male had an oesophago-gastrectomy for Barrett’s oesophagus-associated adenocarcinoma. Prior to the operation he had dysphagia for solids and liquids for several months. He
Rajkumar Vajpeyi MD FRCPC Department of Pathology, Laboratory Medicine Program, University Health Network, University of Toronto, Toronto, Canada. Conflicts of interest: none declared. Runjan Chetty MB BCh FRCPC FRCPath Department of Pathology, Laboratory Medicine Program, University Health Network, University of Toronto, Toronto, Canada. Conflicts of interest: none declared.
DIAGNOSTIC HISTOPATHOLOGY 19:12
Figure 1 A section from the hemicolectomy resection specimen (case 2). The bowel wall appears expanded by submucosal widening due to several cystic spaces. The mesenteric fat is thin and wispy.
457
Ó 2013 Elsevier Ltd. All rights reserved.
INSTRUCTIVE CASE
Figure 2 Lobules of fatty tissue distributed around large vessels (case 1). The fat does not have an infiltrative appearance.
Figure 4 Within the mucoid/myxoid matrix several thin-walled, delicate capillaries were present. This was a dominant feature within all fat lobules.
Pathologic findings Case 1: The hernia sac consisted of unremarkable appearing fibrous tissue measuring 30 25 20 mm.
placed prominent nuclei were discernible and the extremely small atrophic adipocytes had a “signet ring cell” appearance (Figure 3). Most cells were univacuolated with very occasional cells displaying multivacuolation. Occasional nuclei had pseudoinclusions of lipid, so-called “lochkerns”. The nuclei were hyperchromatic but nuclear scalloping and indentation were not seen. The other striking feature was the delicate vascular network of capillaries within the fat lobules (Figure 3). Microscopic examination of case 2 revealed multiple, empty cystic spaces lined by histiocytes and multinucleated giant cells located in the submucosa, subserosa and mesentery (Figure 4). These findings were in keeping with pneumatosis intestinalis. The remainder of the bowel wall, especially the mucosa was intact and within normal limits and a source for the air was not apparent in the bowel.
Case 2: Gross examination of the bowel wall showed it to be thickened with a spongy feel and demonstrable crepitus. The mesentery was described as “bubbly” and appeared to be filled with air (Figure 1). The mucosal surface of the colon appeared unremarkable apart from scattered foci of congestion. Microscopy of case 1 showed fibrous tissue containing large veins and fatty tissue. The unusual appearance of the fat was the most striking feature. The adipocytes were smaller (atrophic) than normal and showed mild variation in size. They were arranged and organized into lobules within the fibrous tissue and around vessels (Figure 2). The stroma between individual adipocytes was prominent and composed of mucoid, amorphous material causing separation of individual fat cells. Peripherally
Figure 5 The bowel wall from case 2 showed intact, normal mucosa. Within the submucosa cystic structures with a surrounding foreign body giant cell response was seen. This is in keeping with pneumatosis intestinalis.
Figure 3 The adipocytes vary in size and shape. Several have eccentrically placed nuclei and resemble signet ring cells. The atrophic fat cells are separated by mucoid material.
DIAGNOSTIC HISTOPATHOLOGY 19:12
458
Ó 2013 Elsevier Ltd. All rights reserved.
INSTRUCTIVE CASE
Perhaps more alarming is the appearance of extremely atrophic adipocytes that resemble signet ring cells of an adenocarcinoma. Once again, the non-infiltrative, lobular arrangement of the signet ring adipocytes is a clue to its non-neoplastic nature. Should there be lingering doubt immunohistochemistry using epithelial markers will confirm the non-epithelial lineage of these signet ring type cells. Of more peripheral interest in case 2 was the association with pneumatosis intestinalis. The patient being extremely malnourished was predisposed to infection with cavities that ruptured leading to pneumothoraces. Air then tracked into the abdominal cavity and bowel wall resulting in pneumatosis intestinalis. The absence of any mucosal defects and/or suppuration induced by gas forming organisms excludes a cause arising within the colon. This short report thus highlights the appearance of “starvation fat” which was seen incidentally along with pathology in the gastrointestinal tract. Lack of awareness of the very characteristic appearance of atrophic adipocytes (signet ring morphology) and intense vascular capillary network with mucoid stromal matrix may invoke a diagnosis of other conditions and indeed, be a source of misdiagnosis. A
Figure 6 The adipocytes from case 2 show more marked atrophy than case 1. Here the adipocytes were all uniformly small with prominent intervening capillaries.
Marked atrophy of adipocytes in the mesenteric fat similar to that encountered in case 1 was also noted. Once again, there was a relative prominence of the vascularity within the lobules of markedly atrophic adipocytes which had a signet ring cell morphology (Figures 5 and 6).
FURTHER READING Brooks JSJ, Perosio PM. Adipose tissue. Musculoskeletal system. Philadelphia. In: Mills SE, ed. Histology for Pathologists 2007; 175e76.
Discussion The changes of starvation and malnutrition in fat cells are rarely encountered in routine diagnostic surgical pathology. In fact, if the appropriate history is not provided and/or sought, the atrophic changes induced by starvation can look alarming, mimic fatty or even epithelial tumours. The prominent delicate capillary network and mucoid/myxoid stroma superficially simulates a myxoid liposarcoma. However, the location of the lesion within the mesentery, the maintenance of the lobular configuration of the fat cells and the absence of a mass lesion all militate against a diagnosis of liposarcoma.
DIAGNOSTIC HISTOPATHOLOGY 19:12
Practice points C C
C C
C
459
Starvation fat can appear incidentally in surgical pathology It is characterized by atrophic adipocytes with retention of a lobular pattern The atrophic fat cells have a signet ring appearance There is prominence of vascularity, especially of the delicate capillary network within the lobules of atrophic fat The stroma contains mucoid/myxoid material
Ó 2013 Elsevier Ltd. All rights reserved.
Starvation-induced fat atrophy in the omentum: a diagnostic pitfall
had a right inguinal hernia since he was a teenager. In order to facilitate his rehabilitation, a repair of the hernia was undertaken. At operation, two hernias were identified: one direct and the other an indirect hernia. The hernia sac was opened and caecum, small bowel and appendix were identified. The hernia was reduced and the bowel contents returned into the abdomen. Since the indirect sac was large, a portion was resected and sent to Pathology. The hernia was repaired and the patient recovered uneventfully. In the course of acquiring more clinical information after the hernia sac was examined microscopically, it was ascertained that the patient had weight loss of over 100 lbs over a 5 month period as a result of the dysphagia and inability to eat.
Rajkumar Vajpeyi Runjan Chetty
Abstract The histological changes encountered in fat as a consequence of starvation are not often encountered in surgical pathology. We present two cases in which the changes in the fat were so striking that other conditions were considered. In both cases weight loss due to decreased intake (dysphagia with oesophageal cancer, and anorexia nervosa) resulted in marked atrophy of fat. The atrophic fatty tissue was noted in tissue sampled in a hernia repair and, in the second case, a hemicolectomy for pneumatosis intestinalis. The atrophic fat was characterized by small signet ring cells suspended in a mucoid/myxoid stroma that contained a very prominent delicate capillary network. This appearance raised suspicion for both signet cell carcinoma and myxoid liposarcoma. However, the lobular noninfiltrative pattern, relevant immunohistochemistry and appropriate clinical history, help reach the correct interpretation.
Case 2 The patient was a 26-year-old woman who reported involuntary weight loss of 50e60 lbs over a year. She was admitted to hospital for weakness and profound malnutrition. On examination, she was cachectic and weighed 70 lbs with a body mass index of 11 kg/m2. Routine laboratory results were in keeping with starvation, and included hypokalaemia (3.0 mmol/L), hypoalbuminaemia (27 g/L), and elevated serum aminotransferases (ALT 307 U/L and AST 274 U/L). There was no evidence of an organic cause for the patient’s severe weight loss. Investigations for diabetes, thyroid disease, malabsorption syndromes, malignancy, and toxicology were all negative. The patient was seen by the Psychiatry service, and was diagnosed with anorexia nervosa. An abdominal ultrasound performed on admission was normal but a CT scan demonstrated extensive intra- and extraperitoneal free air with pneumatosis of the ascending colon. In view of this, a right hemicolectomy was performed. Intraoperatively, there were no signs of perforation, peritonitis, bowel ischaemia/necrosis. A post-operative chest radiograph revealed multiple bilateral cavitary lesions with consolidation and bilateral pneumothoraces. The patient developed progressive respiratory failure and died 1 month after admission. A postmortem examination was not performed.
Keywords atrophy; capillary network; fat; signet ring-like cells; starvation
During periods of starvation or malnutrition, especially when prolonged, atrophy of tissue and organs is the rule. In most sites the actual morphological appearance of organs is not fundamentally altered. In other words, atrophic cardiac muscle, for instance, is still recognizable as cardiac muscle. However, severe atrophy of fatty tissue can alter the appearance of adipocytes to such an extent that it is not readily apparent as fat.1 Fat atrophy is most vividly seen in subcutaneous and omental fat. We present two cases in which there was extreme atrophy of omental fat resulting in morphologic mimicry of other fatty lesions and/or vascular lesions, and hence diagnostic concerns.
Clinical details Case 1 A 55-year-old male had an oesophago-gastrectomy for Barrett’s oesophagus-associated adenocarcinoma. Prior to the operation he had dysphagia for solids and liquids for several months. He
Rajkumar Vajpeyi MD FRCPC Department of Pathology, Laboratory Medicine Program, University Health Network, University of Toronto, Toronto, Canada. Conflicts of interest: none declared. Runjan Chetty MB BCh FRCPC FRCPath Department of Pathology, Laboratory Medicine Program, University Health Network, University of Toronto, Toronto, Canada. Conflicts of interest: none declared.
DIAGNOSTIC HISTOPATHOLOGY 19:12
Figure 1 A section from the hemicolectomy resection specimen (case 2). The bowel wall appears expanded by submucosal widening due to several cystic spaces. The mesenteric fat is thin and wispy.
457
Ó 2013 Elsevier Ltd. All rights reserved.
INSTRUCTIVE CASE
Figure 2 Lobules of fatty tissue distributed around large vessels (case 1). The fat does not have an infiltrative appearance.
Figure 4 Within the mucoid/myxoid matrix several thin-walled, delicate capillaries were present. This was a dominant feature within all fat lobules.
Pathologic findings Case 1: The hernia sac consisted of unremarkable appearing fibrous tissue measuring 30 25 20 mm.
placed prominent nuclei were discernible and the extremely small atrophic adipocytes had a “signet ring cell” appearance (Figure 3). Most cells were univacuolated with very occasional cells displaying multivacuolation. Occasional nuclei had pseudoinclusions of lipid, so-called “lochkerns”. The nuclei were hyperchromatic but nuclear scalloping and indentation were not seen. The other striking feature was the delicate vascular network of capillaries within the fat lobules (Figure 3). Microscopic examination of case 2 revealed multiple, empty cystic spaces lined by histiocytes and multinucleated giant cells located in the submucosa, subserosa and mesentery (Figure 4). These findings were in keeping with pneumatosis intestinalis. The remainder of the bowel wall, especially the mucosa was intact and within normal limits and a source for the air was not apparent in the bowel.
Case 2: Gross examination of the bowel wall showed it to be thickened with a spongy feel and demonstrable crepitus. The mesentery was described as “bubbly” and appeared to be filled with air (Figure 1). The mucosal surface of the colon appeared unremarkable apart from scattered foci of congestion. Microscopy of case 1 showed fibrous tissue containing large veins and fatty tissue. The unusual appearance of the fat was the most striking feature. The adipocytes were smaller (atrophic) than normal and showed mild variation in size. They were arranged and organized into lobules within the fibrous tissue and around vessels (Figure 2). The stroma between individual adipocytes was prominent and composed of mucoid, amorphous material causing separation of individual fat cells. Peripherally
Figure 5 The bowel wall from case 2 showed intact, normal mucosa. Within the submucosa cystic structures with a surrounding foreign body giant cell response was seen. This is in keeping with pneumatosis intestinalis.
Figure 3 The adipocytes vary in size and shape. Several have eccentrically placed nuclei and resemble signet ring cells. The atrophic fat cells are separated by mucoid material.
DIAGNOSTIC HISTOPATHOLOGY 19:12
458
Ó 2013 Elsevier Ltd. All rights reserved.
INSTRUCTIVE CASE
Perhaps more alarming is the appearance of extremely atrophic adipocytes that resemble signet ring cells of an adenocarcinoma. Once again, the non-infiltrative, lobular arrangement of the signet ring adipocytes is a clue to its non-neoplastic nature. Should there be lingering doubt immunohistochemistry using epithelial markers will confirm the non-epithelial lineage of these signet ring type cells. Of more peripheral interest in case 2 was the association with pneumatosis intestinalis. The patient being extremely malnourished was predisposed to infection with cavities that ruptured leading to pneumothoraces. Air then tracked into the abdominal cavity and bowel wall resulting in pneumatosis intestinalis. The absence of any mucosal defects and/or suppuration induced by gas forming organisms excludes a cause arising within the colon. This short report thus highlights the appearance of “starvation fat” which was seen incidentally along with pathology in the gastrointestinal tract. Lack of awareness of the very characteristic appearance of atrophic adipocytes (signet ring morphology) and intense vascular capillary network with mucoid stromal matrix may invoke a diagnosis of other conditions and indeed, be a source of misdiagnosis. A
Figure 6 The adipocytes from case 2 show more marked atrophy than case 1. Here the adipocytes were all uniformly small with prominent intervening capillaries.
Marked atrophy of adipocytes in the mesenteric fat similar to that encountered in case 1 was also noted. Once again, there was a relative prominence of the vascularity within the lobules of markedly atrophic adipocytes which had a signet ring cell morphology (Figures 5 and 6).
FURTHER READING Brooks JSJ, Perosio PM. Adipose tissue. Musculoskeletal system. Philadelphia. In: Mills SE, ed. Histology for Pathologists 2007; 175e76.
Discussion The changes of starvation and malnutrition in fat cells are rarely encountered in routine diagnostic surgical pathology. In fact, if the appropriate history is not provided and/or sought, the atrophic changes induced by starvation can look alarming, mimic fatty or even epithelial tumours. The prominent delicate capillary network and mucoid/myxoid stroma superficially simulates a myxoid liposarcoma. However, the location of the lesion within the mesentery, the maintenance of the lobular configuration of the fat cells and the absence of a mass lesion all militate against a diagnosis of liposarcoma.
DIAGNOSTIC HISTOPATHOLOGY 19:12
Practice points C C
C C
C
459
Starvation fat can appear incidentally in surgical pathology It is characterized by atrophic adipocytes with retention of a lobular pattern The atrophic fat cells have a signet ring appearance There is prominence of vascularity, especially of the delicate capillary network within the lobules of atrophic fat The stroma contains mucoid/myxoid material
Ó 2013 Elsevier Ltd. All rights reserved.