| Assuming that other circulating neutrophils are similar to the band neutrophil in the photograph(see inclusion at arrow tip), which of the following conditions is most likely? | View Page |
| Familial disorders: summary Several additional familial and congenital disorders associated with atypical inclusions in WBCs are now recorded. These individual syndromes carry the following names: Fechtner, Alport, Epstein, Sebastian, and Paris-Trousseau.Fechtner syndrome( Peterson etal,Blood 65:397-406,1985)was described with 8 family members spanning 4 generations presenting with varying degrees of nephritis, deafness,and congenital cataracts. The syndrome is likely a variant of Alport syndrome with the addition of leukocyte inclusions and macrocytothemia. Several more cases involving other families have been reported. The inclusions resemble toxic Doehle bodies or those of the May-Hegglin anomaly by light microscopy, but are ultrastructurally unique.Alport syndrome in itself is autosomal dominant, X-linked , hereditary and characterized by sensorineural deafness and hereditary nephritis. It is believed to result from abnormal glycopeptide synthesis in renal basement membranes. Recurrent hematuria and slowly progressive renal insufficiency are clinical findings. Cataracts and platelet abnormalities may be added features.Epstein syndrome is essentially Alport syndrome with the addition of macrothrombocytopenia (Seri, et al. Hum Genet 110:182-186, 2002). Neutrophil inclusions are absent in this disorder; neutrophilic inclusions are considered part of the Fechtner syndrome. The Sebastian platelet syndrome is a variant of hereditary macrothrombocytopenia combined with neutrophil inclusions that differ from Doehle bodies, but are similar to those inclusions in Fechtner syndrome. (Greinacher, et al, Blut 61:282-288, 1990).Paris-Trousseau syndrome includes large platelets containing giant alpha granules identifiable in the peripheral blood.(Breton-Gorius, Blood 85:1805,1995) | View Page |
| WBC inclusions: summary The presence of atypical inclusions within the cytoplasm of neutrophils and other leukocytes should lead to a clinical investigation of the setting for these findings.Atypical neutrophil inclusions may be seen in the following disorders: Chediak-Higashi syndrome, May-Hegglin anomaly, Alder-Reilly anomaly, Fechtner , Sebastian, Epstein and Alport-like syndromes and in infectious and toxic conditions (in the form of Doehle bodies).Although a specific entity may not be evident from examination of the peripheral blood alone, it is important that hematology technologists include a comment reporting on the presence of these inclusions or granules. A clinical investigation with further hematologic and genetic studies may then appropriately be considered.Many of the disorders with atypical neutrophil cytoplasmic granules are also associated with platelet abnormalities, particularly giant platelets (lower photograph).Therefore, when atypical granules are recognized, scanning of the peripheral blood smear for atypical platelets may be revealing. These observations serve as readily identifiable markers for acquired and genetic human maladies, and as a guide for unraveling the reasons for a patient's suffering and impaired health. | View Page |
| The pale-staining cytoplasmic bodies marked by the arrow in the photograph may be seen in each of the following conditions except: | View Page |
| The May -Hegglin anomaly Illustrated in the upper photograph is a poorly defined cytoplasmic inclusion somewhat resembling a Doehle body. Note, however, that this inclusion is well defined and there is no evidence of toxic granulation in the cytoplasm.When Doehle-like bodies are identified, May-Hegglin anomaly should be considered in the differential diagnosis even though this entity is rare.The May-Hegglin anomaly is an inherited dominant condition in which large 2 - 5 um, basophilic and pyronophilic inclusions are present in granulocytes, including neutrophils, eosinophils, basophils, and monocytes.Similar to Doehle bodies, the May-Hegglin inclusions also are composed of RNA, probably derived from the rough endoplasmic reticulum. May-Hegglin anomaly includes giant platelets containing few fine granules (lower photograph).Sometimes the platelets have bizarre shapes and variable sizes. Variable degrees of thrombocytopenia complicated by mild bleeding problems and purpura may accompany the aberrant platelets. | View Page |
| Case History A 17-year-old young woman was admitted to the hospital with abdominal pain and a tentative diagnosis of appendicitis.The total white blood count was 14,500 cells/cumm with a left shift and neutrophils with changes tagged by the arrow in the photographs (see blue arrow).The bluish-staining, blurred accumulations in the cytoplasm (Doehle bodies), are located at the cell periphery in neutrophils with toxic changes.Doehle bodies are remnants of endocytoplasmic reticulum and are products of cytokine activity in the induction and shortened activity of neutrophil activation.They are often present in conditions with increased neutrophil lysosomal activity, manifest as toxic granulation.In this case, the presence of Doehle bodies serves as markers for infection-induced leukocytosis and supports the diagnosis of acute appendicitis. | View Page |
| Doehle Bodies: Review Doehle bodies are discrete, round or oval aggregates at the cytoplasmic periphery of neutrophils (blue arrows in figures). They stain sky blue with Romanowsky's stain and often may be deceivingly inconspicuous. In electron-micrographs, Doehle bodies are recognized as lamellar aggregates of rough endoplasmic reticulum. Although not considered a marker for leukemia, Goudsmit, et al (Brit J Hematol 20:447-562, 1971)reported their presence in family members, 2 sisters and 3 brothers. Two of the brothers died of acute myeloblastic leukemia. These testimonials indicate that Doehle bodies, when identified in peripheral blood smears, should be taken seriously so as to stimulate a clinical investigation of the patient. | View Page |