Case 42 - Discussion

Uploaded: 2008-01-18, Updated: 2008-01-18

MICROSCOPIC EXAM

PERIPHERAL BLOOD        

WBC 7.67 x 10^3/ul; RBC 2.75 x10^6/uL; Hgb 8.5 g/dl; Hct 25%; MCV 90.9 fl; RDW 15.7; Plt 39 x10^3/ul.
Examination of Wright-Giemsa stained peripheral blood smear reveals moderate normocytic normochromic anemia. Occasional nucleated red blood cells are noted. Neutrophils are normal in number with unremarkable morphology. Rare atypical cells are noted, suspicious for circulating lymphoma cells. Platelets are markedly reduced in number with unremarkable morphology

BONE MARROW CORE BIOPSY AND CLOT SECTION:

Quality: Adequate.
The bone marrow is hypercellular (90-100%) and diffusely infiltrated by sheets of large cells with round nuclear contour, prominent nucleoli, scant to moderate cytoplasm. There are frequent mitotic figures and focal "starry sky" appearance. The atypical cells account for 80% of the overall cellularity. Multiple scattered focus of trilineage hematopoiesis is present. Few clusters of small lymphocyte aggregate is also noted in the clot section, which contains small lymphocytes with irregular nuclei contour, clumped chromatin and scant amount of cytoplasm.   

BONE MARROW ASPIRATE SMEAR AND TOUCH IMPRINTS:

Quality: Adequate, hypercellular with spicules.
M:E ratio: 3:1
Myeloid lineage: Orderly maturation with toxic granulation.
Erythroid lineage: unremarkable morphology.
Megakaryocytes present.
Other findings: An abnormal population of large atypical cells with high N/C ratio, round nuclear contour, prominent nucleoli and moderate amount of basophilic cytoplasm is noted (35%).Some
of the malignant cells show eccentrically located nuclei 

SPECIAL STAINS:
Iron stain (bone marrow smear, clot section and core section ): Stainable iron is present. No ringed sideroblasts are present.
PAS stain (core section): Similar to H&E stain.
Reticulin stain (core biopsy): Marked diffuse reticulin fibrosis, 3+/3+.

FLOW CYTOMETRY INTERPRETATION

There are two aberrant populations of cells identified on flow cytometry.  The first aberrant population of cells express dim CD45, CD38, CD138, CD8, dim partial cytoplasmic CD79a, and surface and cytoplasmic monotypic light chain kappa, which account for 27% of the total events analyzed.  The second population account for 10% of the total events analyzed and express CD19, CD5, CD23 and monotypic surface kappa light chain.  The immunophenotype for the second population is consistent with B-cell small lymphocytic lymphoma/chronic lymphocytic leukemia.  The immunophenotype of the first population of cells is consistent with large cell lymphoma of B-cell lineage with plasmablastic differentiation.

			H gate Dim CD45+	A gate Bright CD45+
 Total events      	events = 18579    	events = 7245
 analyzed = 78464	(27% of total)	        (10% of total)

  CD45+/CD14-		 100%			99%
  CD14+			  <2%
  Total CD13+		   2%
  CD13+/CD34+		  <2%
  Total CD15+		  <2%
  CD15+/CD34+		  <2%
  Total CD33+		  <2%
  CD33+/CD34+		  <2%
  Total CD34+  		  <2%
  Total HLA DR+		   7%
  HLA-DR+/CD34+		  <2%
  Total CD117+		   7%
  CD117+/CD34+		  <2%
  CD19+/CD3-		  <2%			62%
  CD3+/CD19-		  <2%			20%
  CD19+CD20+		  <2%			<2%
  Total CD38+		  98%			28%	
  CD19+/CD38+		  <2%			 3%
  CD19+/CD10+		  <2%			<2%
  CD5+/CD19+		  <2%			70%
  CD5+/CD19-		  <2%			 5%
  CD19+/CD23+		  <2%			60%
  CD19+/FMC7+		  <2%			<2%
  Total CD26+		   2%			 5%
  CD2+/CD7+		  <2%			15%
  CD3+/CD5+		   5%			16%
  CD3+/CD4+		  <2%			 9%
  Total CD8+		  87%			11%
  CD3+/CD8+		  14%			 4%
  Total CD16+		   2%			 7%
  CD3-/CD56+		  <2%			 7%
  sIg Kappa+		 100%			80%
  sIg Lambda+		  <2%			<2%
  cCD3+			  <2%
  cCD79a+		  34%
  cCD19+		  <2%
  cMPO+			  31%
  cTdT+			   4%

                 Gated on CD19+ cells
  CD19+/sIg Kappa+		96%
  CD19+/sIg Lambda+		 2%

			A gate Bright		 
 Total events  		CD38+/CD138+ events =             	
 analyzed = 42112	9355 (22% of total)

  CD45+/CD38+		  94%                                		
  CD38+/CD19+		  <2%		
  CD38+/CD117+		  <2%

                 Gated on CD138+ cells
  CD138+/cIg Kappa+	  56%
  CD138+/cIg Lambda+	  <2%

IMMUNOHISTOCHEMISTRY STAINS

IN SITU HYBRIDIZATION

CYTOGENETICS (UNMC, Cytogenetics)

Cytogenetic analysis revealed the presence of an abnormal hypertriploid clone characterized by the gain of chromosomes S, Y, 1, 7, 12, 13, 19, 22; loss of chromosomes 4 and 6; interstitial deletions of 1p and 5q; additional material of unknown origin on 11p; reciprocal translocations involving 8q and 14q, and 12q and 14q; four derivative chromosomes resulting from unbalanced translocations involving 12q and 14q and a complex rearrangement of 8q, 14q and 21p; and this presence of two marker chromosomes. One abnormal cell characterized by t(12;14) represents the primary clone.

NOMENCLATURE: 46,XY,t(12;14)(q14;q32)[1]/78,XXY,+X,+Y,+del(1)(p22p36.1),-4,del(5)
(q12q33),-6,+7,+7,t(8;14)(q24.1;q32),der(8)y(8;14),
add(11)(p15.5),t(12;14)(q13;q32),+der(12)t(12;14),
+13.der(14)t(8;14)t)14;21)(q22;p13),+19,der(21)t(8;14)t(14;21),+22,
+mar1,+mar2[16]/46,XY[3]

Molecular cytogenetic studies detected a complex rearrangement of the IgH region at 14q32 in 98%, a rearrangement of the c-MYC region at 8q24 in 87% and 3 copies of the ALK region at 2p23 in 89% of the interphase cells from this specimen. Interphase FISH studies were negative for a rearrangement of the ALK (2p23) region. These results are consistent with the abnormal clone see in this patient's G-band study.

DIAGNOSIS

• Plasmablastic lymphoma transformed from preceding CLL/SLL