Case 344 -- Sinus pressure, headache and gingival hyperplasia

Contributed by Sourav Ray, MD and Sandra Kaplan, MD
Published on line in March 2003


PATIENT HISTORY:

A 30-year-old female without any significant past medical history developed symptoms of sinus pressure and headache for approximately three weeks. These were thought to be sinusitis and treated with oral antibiotics (bactrim) and antihistamines. Subsequently she developed gingival hyperplasia and was found to have a white blood cell count of over 70x10^9/L.

PB Counts:

WBC

78 x 10^9/L

(normal 3.8 10.6 x10^9/L)

RBC

2.69 x10^12/L

(normal 3.73 4.89 x10^12/L)

Hemoglobin

9.0 g/dl

(normal 11.6 14.6 g/dl)

Hematocrit

25.6 %

(normal 34.1 43.3 %)

MCV

95.4 fl

(normal 82.6 97.4 fl)

MCH

33.5 pg

(normal 27.8 33.4 pg)

MCHC

35.1 g/dl

(normal 32.7 35.5 g/dl)

RDW

14.6 %

(normal 11.8 15.2 %)

PLT

43 x10^9/L

(normal 156 369 x10^9/L)

POLYS

1 % ; ABS 0.8

(normal 2.24 7.68)

LYMPHS

13%; ABS 10.0

(normal 0.80 3.65)

MONOS

25%; ABS 23.3

(normal 0.30 0.90)

EOS

16%; ABS 10.6

(normal 0.00 0.40)

BLASTS

40%; ABS 29.2

 

PRO

1%; ABS 0.8

 

MYELO

2%; ABS 1.60

 

META

2%; ABS 1.60

 

The peripheral blood smear was reviewed and showed generally unremarkable red blood cell morphology and decreased numbers of platelets (Fig. 1). White blood cell morphology showed many blasts that varied in size, nuclear contours, and amount of cytoplasm (Figs. 2 and 3). Nuclear contours varied from round to convoluted. The cytoplasm was generally moderate but some cells had somewhat less and others had somewhat more. Chromatin was generally dispersed and some of the cells exhibited a nucleolus. Many eosinophils were present including immature forms particularly eosinophilic myelocytes (Fig. 4). Also many monocytoid cells with light blue vacuolated cytoplasm and irregular nuclear contours were noted (Fig. 5).

Bone Marrow biopsy (Figs. 6 and 7) and aspirate (Figs. 8 and 9) were performed with the following remarkable and abnormal differential counts:

Blasts

67%

(normal 0.0 2.0)

Eos Myelo/Meta

15%

(normal 1.0 4.0)

Eos Band

3.7%

(normal 1.0 2.0)

Eos Seg

2.3%

(normal 1.0 2.0)

The marrow was markedly hypercellular (approximately 100%) (Fig. 6). The predominant cells were blasts but eosinophils also appeared markedly increased (Fig. 7). The blasts in the marrow were generally large with many having a moderate amount of medium to light blue cytoplasm. The nuclear chromatin was dispersed or partially dispersed but usually without a nucleolus.

Ancillary Studies:

Approximately 10% of the young cells appeared to be reactive for peroxidase a histochemical marker for myeloid differentiation (Fig. 10). Approximately 10% of the blasts were weakly positive for nonspecific esterase (NSE) a histochemical marker for monocytoid differentiation (Fig. 11). Greater that 50% of cells were positive for CD68 an immunohistochemical marker for myeloid cells and especially macrophages (Fig. 12). Approximately 30% of cells were positive for lysozyme another immunohistochemical marker for myeloid and particularly monocytoid lineage cells (Fig. 13).

Flow Cytometry:

Flow cytometric immunophenotyping studies performed on bone marrow demonstrated numerous CD34 positive/CD117 positive myeliod blasts (14/22% positive); these cells coexpressed the myeloid markers CD13/33 (Figs. 14 and 15). Many expressed HLA-DR and TdT, also markers of myeloid immaturity (Figs. 16 and 17). Also, there was a distinct population of cells that expressed the monocytoid marker, CD14 (Fig. 18).

Cytogenetics and FISH:

Conventional karyotypic analysis suggested initially that one cell line represented by most of the examined cells showed a translocation between the long arms of chromosomes 5 and 22. Specifically 46XX t(5;22)(q31;q11.2). However, FISH studies performed subsequently suggested a more complex three-way translocation involving chromosomes 12,5, and 22: [t(5;12,22)(q33;p13;q13)]. FISH studies utilized the ERG1(5q31), the telomeric DNA probes for 5q and 22q, and the TEL DNA (12p13) probes to further elucidate the breakpoints. These studies showed that one 5qtel signal was translocated from the der(5) to the der(22) (Seimon5q.tif) and one 22qtel signal was translocated form the der(22) to the short arm of chromosome 12 (Seimon22q.tif), and one TEL signal was translocated from the short arm of der(12) to the long arm of der(5). The FISH findings confirmed a complex three-way translocation involving the short arm of chromosome 12 in addition to the long arms of chromosomes 5 and 22 as was detected by classical cytogenetics. The EGR1(5q31) probe showed that the EGR1 gene locus was preserved on the der(5) suggesting that the breakpoint was distal to the ERG1 locus therefore modifying the karyotype to be 46,XX,t(5;12;22)(q33;p13;q13) (Figs. 19, 20 and 21)

FINAL DIAGNOSIS


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