[Skip to Navigation]
Sign In
Special Feature
May 2001

Pathological Case of the Month

Arch Pediatr Adolesc Med. 2001;155(5):611-612. doi:10.1001/archpedi.155.5.611

Diagnosis and Discussion: Shwachman-Diamond Syndrome: A Syndrome of Pancreatic Insufficiency and Bone Marrow Dysfunction

Figure 1. Normal architecture of the pancreas is lost. It is soft and mucinous to the touch.

Figure 2. Extensive replacement of pancreatic tissue by adipose tissue and few scattered remnants of the pancreatic tissue (hematoxylin-eosin, original magnification ×55).

Figure 3. Remnants of pancreatic tissue composed of proliferated ducts and relative increase of islets of Langerhans (hematoxylin-eosin, original magnification ×140).

Figure 4. Atrophic and shrunken acinar tissue with cells having a pink cytoplasm and pyknotic nuclei (hematoxylin-eosin, original magnification ×280).

Shwachman-Diamond syndrome1-4 is the second most common cause of pancreatic insufficiency in early life after cystic fibrosis. Pancreatic exocrine insufficiency is accompanied by growth retardation, bone marrow dysfunction with neutropenia, and skeletal changes, predominantly metaphyseal dysostosis. Sweat chloride test findings are normal. Cases have been associated with anal atresia,4,5 Hirschsprung disease,6 and asphyxiating thoracic dystrophy.7 The bone marrow dysfunction is associated with the eventual appearance in some cases of leukemia, usually nonlymphocytic.8-10 Cases have been reported in which the clinical onset of pancreatic insufficiency occurred soon after birth2,7 and includes malabsorption, steatorrhea, and failure to thrive. More than 25 families had at least 2 affected children, and the inheritance is presumed to be autosomal recessive. Many patients develop anemia (15%) or thrombocytopenia (7%) or both (20%). Occasionally, anemia and thrombocytopenia precede neutropenia. In this condition the neutrophils may not be totally normal. There may be a defect in neutrophil mobility, which may explain infection even when the neutrophil count is not extremely low. Histopathologic analysis reveals the bulk of the pancreas to be replaced by fatty tissue.3 Pancreatic ducts and endocrine elements are preserved.11 Usually the acinar is absent,11 but occasionally some acinar cells are present and are large and devoid of secretary granules.1 Occasionally, atrophic acinar tissue is seen with pink cytoplasm and pyknotic nuclei.

The relationship of the pancreatic insufficiency to the hematologic abnormalities remains unknown. Pancreatic insufficiency from other causes such as cystic fibrosis is not associated with neutropenia. Pancreatic replacement therapy does not improve the neutropenia in Shwachman-Diamond syndrome. An injury or insult during the fifth fetal month, when development of both the pancreatic exocrine tissue and the myeloid population in the bone marrow occurs, may explain this association. However, familial cases suggest that the disorder is inherited as an autosomal recessive trait.

In this index case, the clinical onset of pancreatic insufficiency occurred soon after birth. The pancreatic replacement therapy did not improve the neutropenia. Anemia responded to therapy and blood transfusion. Repeated infections occurred, but growth and weight gain were within normal limits.

Patients with pancreatic insufficiency with normal sweat electrolytes and lack of respiratory disease should be evaluated for Shwachman-Diamond syndrome. These patients seem to have a better prognosis than those with cystic fibrosis.

Accepted for publication May 24, 1999.

Reprints: Nandita Kakkar, MD, Department of Histopathology, PGIMER, Chandigarh 160012, India.

Shwachman  HDiamond  LKOski  FAKhaw  K-T The syndrome of pancreatic insufficiency and bone marrow dysfunction.  J Pediatr. 1964;65645- 663Google ScholarCrossref
Hoyer  A Lipomatous pseudohypertrophy of the pancreas with complete absence of exocrine tissue.  J Pathol Bacteriol. 1949;6193- 100Google ScholarCrossref
Bodian  MSheldon  WLightwood  R Congenital hypoplasia of the exocrine pancreas.  Acta Paediatr (Scand). 1964;53282- 293Google ScholarCrossref
Lumb  GBeautyman  W Hypoplasia of the exocrine tissue of the pancreas.  J Pathol Bacteriol. 1952;64679- 686Google ScholarCrossref
Townes  PL Proteolytic and lipolytic deficiency of the exocrine pancreas.  J Pediatr. 1969;75221- 228Google ScholarCrossref
Burke  VColebatch  JHAnderson  CMSimons  MJ Association of pancreatic insufficiency and chronic neutropenia in childhood.  Arch Dis Child. 1967;42147- 157Google ScholarCrossref
Karjoo  MKoop  CECornfeld  DHoltzapple  PG Pancreatic exocrine enzyme deficiency associated with asphyxiating thoracic dystrophy.  Arch Dis Child. 1973;48143- 146Google ScholarCrossref
Aggett  PJCavanagh  NPCMatthew  DJPincott  JRSutcliffe  JHarries  JT Shwachman's syndrome: a review of 21 cases.  Arch Dis Child. 1980;55331- 347Google ScholarCrossref
Huijgens  PCvan der Veen  EAMeijer  SMuntinghe  OG Syndrome of Shwachman and leukemia.  Scand J Haematol. 1977;1820- 24Google ScholarCrossref
Strevens  MJLilleyman  JSWilliams  RB Shwachman's syndrome and acute lymphoblastic leukemia.  BMJ. 1978;218Google ScholarCrossref
Seifert  G Lipomatose cystiche Pankreasfibrose und lipomatose Pankreatrophie des Kindesalters.  Beitr Pathol Anat. 1959;12164- 80Google Scholar