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Transient myeloproliferative disease of the newborn: Case report with placental, cytogenetic, and flow cytometric findings
HUMAN PATHOLOGY
Volume 31, No. 3 (March 2000)
TRANSIENT MYELOPROLIFERATIVE DISEASE OF THE NEWBORN: CASE REPORT WITH PLACENTAL, CYTOGENETIC, AND FLOW CYTOMETRIC FINDINGS MICHAEL W. DE TAP. MD, WILLIAMDITTMAN, MD, ANn JoYcE GILBERT, MD
Transient myeloproliferative disease (TMD) of the newborn is a rare hematologic abnormality associated with trisomy 21. It is frequently difficult to distinguish the disorder from true congenital leukemia (TCL). Unlike leukemia, which has a clinically aggressive course, TMD generally resolves within weeks to months. We present a case of TMD of the newborn diagnosed on the basis of peripheral blood studies and describe the pertinent pathological findings within the placenta. Flow cytometric analysis of the blasts in the peripheral blood showed phenotypic heterogeneity with features consistent with megakaryocytic differentiation. Cytogenetic studies showed trisomy
21 within the blastic cells. The placenta showed villous dysmaturity with associated chorangiosis and prominent intravascular aggregates of primitive-appearing cells with focal, early vascular wall invasion. The neonate recovered fully and shows no evidence of disease at 2 years of age. HUM PATnOL 31:396-398. Copyright © 2000 by W.B. Samlders Company Key words: placenta, transient myeloproliferative disease, trisomy 21, congenital leukemia. Abbreviations: TMD, transient myel0proliferatlve disease; TCL, true congenital leukemia; DS, Down's syndrome
Transient Myeloproliferative Disease of the newborn (TMD) is a well described hematologic abnormality seen almost exclusively associated with trisomy 21. Most neonates with TMD show evidence of Down's syndrome (DS), which are either pure or mosaic. Rarely, genotypically normal children with an isolated expansion of immature cells with the trisomy 21 genotype have been described. 1,z The affected neonates show markedly elevated leukocyte counts on evaluation of the peripheral blood, with a majority of cells showing blastic morphology. Flow cytometric analyses will generally show monoblastic and myelomonoblastic populations, however, phenotypic heterogeneity is common. Expression of megakaryocytic antigens is commonly found, and occasional cases show a lymphoblastic phenotype. 3 The placental findings of TMD have not been previously described. We report the placental and hematologic findings in a newborn with TMD, including flow cytometric and cytogenetic studies.
44.4%; mean corpuscular volume (MCV), 123.7 fL; and platelets, 286 × 109/L. The differential showed 13% neutrophils, 1% bands, 15% lymphocytes, 5% monocytes, 1% promyelocytes, 88 nucleated red blood cells (nRBC)/100 WBC, and 65% blasts. Flow cytometric analysis of the peripheral blood showed positivity for CD33 and CD34, with dim CD4 positivity, but negativity for CD13, CD14, HLA-DR, and myeloperoxidase. Markers specific for megakaryocytic antigens were not used. Lymphoid markers (CD3, CD10, CD19, CD20, and terminal deoxytransferase) were negative. Mature monocytic, lymphocytic, and granulocytic cells showed normal antigen expression. Cytogenetic studies on the peripheral blood showed typical trisomy 21 in all cells examined. Additional cytogenetic abnormalities were not identified. The peripheral blood abnormalities resolved within the next 3 weeks, and a repeat CBC performed at 6 weeks of age showed a total WBC count of 7.6 X 109/L with a normal differential and 3 nRBC/100 WBC. No blasts were identified. The infant is alive and well at 2 years of age.
CASE REPORT
Clinical History The mother was a 35-year-old RH-positive white woman who spontaneously delivered a 3,459-g female at approximately 35 weeks of gestational age. The pregnancy was unremarkable except for mild polyhydramnios developing a few weeks before delivery. The initial physical exam was notable for obvious stigmata of Down's syndrome and a purpuric macular rash on the neonate's back, which resolved over the first 6 weeks of life. Chemistry studies on the second postnatal day showed the following: albumin, 3.2 g/dL; alkaline phosphatase, 291 IU/L; total bilirubin, 25.1 m g / d L ; direct bilirubin, 2.0 m g / d L ; AST, 114 IU/L; ALT, 480 IU/L; LDH, 3,420 IU/L; and GGTP, 7 IU/L. The hyperbilirubinemia peaked the following day at 25.8 but responded well to phototherapy which was required for 6 days.
Hematologic Findings The complete blood count (CBC) on the first postnatal day showed the following: WBC, 151.6 × 10e/L; RBC, 3.60 × 1012/L; hemoblogin (HGB), 13.8 g/dL; hematocrit (HCT), From Pathology Associates, Inc, RS., and Sacred Heart Medical Center, Spokane, WA; and Bonner General Hospital, Sandpoint, ID. Address correspondence and reprint requests to Michael de Tar, MD, Pathology Associates Inc, ES., 11604 East Indiana Ave, Spokane, WA 99206. Copyright © 2000 by W.B. Saunders Company 0046-8177/00/3103-0021510.00/0 doi: I0.1053/hp.2000.5206
396
Placental Findings The placenta was examined according to standard protocol. After trimming of membranes and removal of the umbilical cord, The formalin-fixed placenta weighed 572 g and showed apparent meconium staining. The trivascular umbilical cord and villous parenchyma were grossly unremarkable. Microscopically, the placenta was free of inflammation, although the vessels of the umbilical cord and chorionic plate contained numerous blasts and a moderate erythroblastosis. Occasional aggregates were attached to the endothelial lining of the vessels within villous trunks and showed early organizing thrombus formation (Fig 1). The chorionic villi showed early third trimester maturation patterns with abnormally increased numbers of more rounded, bulky villous forms and an associated, generalized villous hypervascularity consistent with "chorangiosis" (Fig 2). The villous stroma did not show tissue infiltration by primitive blast forms, nor was there evidence of chronic villitis. A few larger vessels of the chorionic plate showed a circumferential pattern of endothelial and subendothelial margination of primitive cells (Fig 3). Focal, early vascular wall invasion with associated fibrinoid necrosis of the intima was present within a few of these vessels. These areas also showed an associated apoptosis of primitive cells (Fig 4). This finding was only focally identified in just 2 of the multiple sections examined.
CASE STUDIES
FIGURE 1. Intravascular organizing thrombus containing blasts. (Original magnification × 100.)
FIGURE 3. Circumferential pattern of early vascular wall invasion. (Original magnification x50.)
DISCUSSION True congenital leukemia (TCL) is a rare pediatric malignancy representing less than 1% of all pediatric leukemias. 4 Approximately 200 cases have been reported, with a n u m b e r of these likely representing the more indolent and benign transient myeloproliferative disease of infancy.5 The clinical criteria for a diagnosis of TCL traditionally have included: (1) manifestations during the first 4 to 6 weeks of life; (2) proliferation of immature myeloid, lymphoid, or erythroid cells; (3) infiltration of these cells into nonhematopoetic tissues; and (4) absence of other diseases of differential diagnostic importance, such as erythroblastosis fetalis and congenital infections.6 Distinction of TMD from TCL on the basis of morphological parameters alone is difficult. In both abnormalities, the peripheral blood is characterized by a markedly elevated WBC count with numerous blasts present. Infants affected by TCL are generally in poor clinical condition at presentation, and the prognosis is poor. 5'7,s Pronounced hepatosplenomegaly is common in TCL. Autopsy studies on stillborns show evidence of significant tissue infiltration by leukemic cells. Involvement of the skin by leukemic infiltrates is commonly seen in TCL, occurring in up to 30% to 50% of cases. 9,1° The clinical appearance of the skin lesions in the classic case of TCL is of multiple red-blue nodules with a generalized pattern of
distribution ("blueberry muffin lesions"), although papular and macular lesions have also been described. 9 Neonates with TMD are generally healthier clinically, only rarely show skin involvement, and show only mild to moderate degrees of hepato-splenomegaly. Classic "blueberrymuffin" lesions have not been described in TMD, although erythematous plaques and rashes have. 1° The peripheral blood abnormalities generally resolve within weeks to months, although recurrences with spontaneous remissions have been reported. While the prognosis for TMD is generally good, up to 25% of these patients will develop a true leukenlia, usually within the first 3 years of life. 11,12 Many of these leukemias are of the megakaryoblastic lineage (FAB-M7), which is the most common form of leukemia that develops in children with DS. 12 The placenta is a rare site of neoplastic involvement by fetal malignancy, and metastatic neuroblastoma is the most common congenital tumor to spread to this site. a3The pattern of involvement in metastatic neuroblastoma is primarily intravascular, with the fetal vessels of the umbilical cord, chorionic plate, and chorionic villi showing distention by malignant cells. There are only a few reports describing the pathological findings of TCL within the placenta. 8,1~The placenta typically will show massive chorionic tissue infiltration by blast cells, although a well documented case of fatal TCL showed only an intravascular distribution of these cells. The corresponding
FIGURE 2. Chorangiotic villi with intravascular blasts. (Original magnification x200.)
FIGURE 4. Subendothelial aggregates of blasts with apoptotic cells. (Original magnification x 1000.)
397
HUMAN PATHOLOGY
Volume 31, No. 3 (March 2000)
fetal visceral o r g a n s in this case s h o w e d massive infiltration by blastic cells. 8 T h e p l a c e n t a l findings o f T M D have not, to o u r knowledge, b e e n previously described. T h e p l a c e n t a was s o m e w h a t e n l a r g e d for gestational age, a c o m m o n f i n d i n g in t h i r d t r i m e s t e r placentas of DS infants. Erythroblastosis has b e e n d e s c r i b e d in p l a c e n t a s of n e o n a t e s with DS. A similar p a t t e r n o f a b n o r m a l i t y may b e s e e n in t h o s e c o n d i t i o n s associated with fetal-based red-cell destructive processes o r survival defects ( i m m u n e m e d i a t e d hemolysis, glucose-6-phosphorylase deficiency, parvovirus infection, etc.). Differential diagnostic c o n s i d e r a t i o n s o f t h e p l a c e n t a l a b n o r m a l i t i e s in t h e a b s e n c e o f clinical h i s t o r y i n c l u d e a non-specific l e u k o e r y t h r o b l a s t i c reaction, metastasis f r o m a solid fetal malignancy, a n d TCL. T h e significance of early tissue infiltration in t h e p r e s e n t case is u n k n o w n a n d n e e d s f u r t h e r study. Massive tissue infiltration o f n o n - h e m a t o p o e t i c tissues by neoplastic cells is a characteristic finding in fetal tissue of TCL. T h e placenta is a n ideal organ to evaluate for this diagnostic finding b u t is unfortunately only rarely examined. T h e issue of w h e t h e r early tissue infiltration indicates a greater risk for the d e v e l o p m e n t of a true leukemia needs to be addressed. Additional studies o n r o u t i n e l y collected p l a c e n t a s f r o m pregn a n c i e s c o m p l i c a t e d by t r a n s i e n t myeoloproliferative disease are n e e d e d . T h e p a t h o l o g i c a l e x a m i n a t i o n o f all placentas f r o m p r e g n a n c i e s associated with trisomy 21 is r e c o m mended.
REFERENCES 1. Weinberg AG, Schiller G, Windmiller J: Neonatal leukemoid reaction. An isolated manifestationof mosaic trisomy21. AmJ Dis Child 136:810-311, 1982 2. Ridgway D, Benda GI, Magenis E, et al: Transient myeloproliferative disorder of the Down type in the normal newborn. AmJ Dis Child 144:11171119, 1990 3. McCoyJP, Overton WR: Immunophenotyping of congenital leukemia. Cytometry 22:85-88, 1995 4. Pavlucci G, Rosito P: Neonatal myeloproliferative disorders in Dowlr's syndrome and congenital Ieukemias. Hematalogica 72:121-125, 1987 (suppl) 5. Fong C, Brodeur G: Down's Syndrome and Leukemia: Epidemiology, genetics, cytogenetics and mechanisms of leukemogenesis. Cancer Genet Cytogenet 28:55-76, 1987 6. Heikinheimo N, Pakkala S,Juvonen E, et al: Immuno- and cytochemical characterization of congenital leukemia: A case report. Med Pediatr Oncol 22:279-282, 1994 7. McCoyJE Travis S, Blumstein L, et al: Congenital Leukemia: Report of two cases. Cytometry 22:89-92, 1995 8. Gray ES, Balch NJ, Kohler H, et ah Congenital leukemia: An unusual cause of stillbirth. Arch Dis Child 61:1001-1006, 1986 9. Resnick KS, Brod BB: Leukemia cutis in congenital leukemia. Analysis and review of the world literature with report of an additional case. Arch Dermatol 129:1301-1306, 1993 10. Pierce MI: Leukemia in the newborn infant. J Pediatr 54:691-706, 1959 11. Bhatt S, Schreck R, Graham J, et al: Transient Leukemia with Trisomy 21: Description of a case and review of the literature. Am J Med Genet 58:310-314, 1995 12. ZipurskyA, Peeters M, Poon A: Megakaryoblasticleukemia and Down's syndrome: A review. Pediatr Hematol Oncol 4:211-230, 1987 13. Las Heras J, Leal G, Haust D: Congenital leukemia with placental involvement. Cancer 58:2278-2281, 1986
UTERINE MYXOID LEIOMYOSARCOMA WITHIN A LEIOMYOMA KHUSH MITTAL, MD, DOROTA POPIOLEK, MD, AND RITA I. DEMOPOULOS, MD
A case of myxoid leiomyosarcoma of the uterus arising in a leiomyoma is reported. Although the tumor showed very low mitotic activity ranging from zero to 2/10 HPF, the presence of infiltrative pattern of growth and a high MIB-1 index (60% of cells positive)
established the diagnosis. Myxoid leiomyosarcoma may arise in leiomyoma. HUM PATHOL 31:398-400. Copyright © 2000 by W.B. Saunders Company Key words: leiomyoma, myxoid, leiomyosarcoma, uterus, MIB-1.
Myxoid l e i o m y o s a r c o m a o f t h e u t e r u s is a rare n e o p l a s m with only 12 cases r e p o r t e d to date. 1-6 We r e p o r t a case o f m y x o i d l e i o m y o s a r c o m a arising in a leiomyoma. T h e case is b e i n g r e p o r t e d for 3 reasons: (1) to p o i n t o u t t h a t a leiomyos a r c o m a may arise in a leiomyoma; (2) to e m p h a s i z e t h e i m p o r t a n c e o f i n c l u d i n g l e i o m y o s a r c o m a in differential diagnosis o f l e i o m y o m a s with m y x o i d a p p e a r a n c e ; a n d (3) to illustrate t h e fact t h a t a l t h o u g h s o m e m y x o i d leiomyosarcomas have a low mitotic c o u n t , t h e overall proliferative activity as i n d i c a t e d by MIB-1 e x p r e s s i o n may b e high.
cystic t u m o r e x t e n d i n g into t h e m i d - a b d o m e n with displacem e n t o f t h e u t e r u s to t h e left. T h e clinical differential diagnosis was ovarian n e o p l a s m versus leiomyosarcoma. T h e CA 125 s e r u m level was 11. P r e o p e r a t i v e e n d o m e t r i a l biopsy failed to o b t a i n e n d o m e t r i a l tissue. At s u r g e r y a large (30 cm)
CASE R E P O R T A 73-year-old m u l t i p a r o u s w o m a n (G4P3013) whose m e n o p a u s e o c c u r r e d at age o f 50 p r e s e n t e d with 30-1b w e i g h t loss over 1 year a n d i n c r e a s i n g a b d o m i n a l g i r t h for 2 m o n t h s . C o m p u t e d t o m o g r a p h y scan s h o w e d mostly solid a n d partially
From the New York University School of Medicine and Kaplan Cancer Center, NewYork, NY. This work was supported in part by Kaplan Cancer Center Grant No. P30 CA16087. Address correspondence and reprint requests to Khush Mittal, MD, Department of Pathology, 4W35B, Bellevue Hospital, 27th Street and 1st Avenue, NewYork, NY 10016. Copyright © 2000 by W.B. Saunders Company
FIGURE I.
Portion of the cut surface of the tumor showing myxoid confluent nodules of leiomyosarcoma (larger arrow) surrounded by leiomyoma (smaller arrow).
0046-8177/00/3103-0022510.00/0 doi: 10.1053/hp.2000.5207
398
Volume 31, No. 3 (March 2000)
TRANSIENT MYELOPROLIFERATIVE DISEASE OF THE NEWBORN: CASE REPORT WITH PLACENTAL, CYTOGENETIC, AND FLOW CYTOMETRIC FINDINGS MICHAEL W. DE TAP. MD, WILLIAMDITTMAN, MD, ANn JoYcE GILBERT, MD
Transient myeloproliferative disease (TMD) of the newborn is a rare hematologic abnormality associated with trisomy 21. It is frequently difficult to distinguish the disorder from true congenital leukemia (TCL). Unlike leukemia, which has a clinically aggressive course, TMD generally resolves within weeks to months. We present a case of TMD of the newborn diagnosed on the basis of peripheral blood studies and describe the pertinent pathological findings within the placenta. Flow cytometric analysis of the blasts in the peripheral blood showed phenotypic heterogeneity with features consistent with megakaryocytic differentiation. Cytogenetic studies showed trisomy
21 within the blastic cells. The placenta showed villous dysmaturity with associated chorangiosis and prominent intravascular aggregates of primitive-appearing cells with focal, early vascular wall invasion. The neonate recovered fully and shows no evidence of disease at 2 years of age. HUM PATnOL 31:396-398. Copyright © 2000 by W.B. Samlders Company Key words: placenta, transient myeloproliferative disease, trisomy 21, congenital leukemia. Abbreviations: TMD, transient myel0proliferatlve disease; TCL, true congenital leukemia; DS, Down's syndrome
Transient Myeloproliferative Disease of the newborn (TMD) is a well described hematologic abnormality seen almost exclusively associated with trisomy 21. Most neonates with TMD show evidence of Down's syndrome (DS), which are either pure or mosaic. Rarely, genotypically normal children with an isolated expansion of immature cells with the trisomy 21 genotype have been described. 1,z The affected neonates show markedly elevated leukocyte counts on evaluation of the peripheral blood, with a majority of cells showing blastic morphology. Flow cytometric analyses will generally show monoblastic and myelomonoblastic populations, however, phenotypic heterogeneity is common. Expression of megakaryocytic antigens is commonly found, and occasional cases show a lymphoblastic phenotype. 3 The placental findings of TMD have not been previously described. We report the placental and hematologic findings in a newborn with TMD, including flow cytometric and cytogenetic studies.
44.4%; mean corpuscular volume (MCV), 123.7 fL; and platelets, 286 × 109/L. The differential showed 13% neutrophils, 1% bands, 15% lymphocytes, 5% monocytes, 1% promyelocytes, 88 nucleated red blood cells (nRBC)/100 WBC, and 65% blasts. Flow cytometric analysis of the peripheral blood showed positivity for CD33 and CD34, with dim CD4 positivity, but negativity for CD13, CD14, HLA-DR, and myeloperoxidase. Markers specific for megakaryocytic antigens were not used. Lymphoid markers (CD3, CD10, CD19, CD20, and terminal deoxytransferase) were negative. Mature monocytic, lymphocytic, and granulocytic cells showed normal antigen expression. Cytogenetic studies on the peripheral blood showed typical trisomy 21 in all cells examined. Additional cytogenetic abnormalities were not identified. The peripheral blood abnormalities resolved within the next 3 weeks, and a repeat CBC performed at 6 weeks of age showed a total WBC count of 7.6 X 109/L with a normal differential and 3 nRBC/100 WBC. No blasts were identified. The infant is alive and well at 2 years of age.
CASE REPORT
Clinical History The mother was a 35-year-old RH-positive white woman who spontaneously delivered a 3,459-g female at approximately 35 weeks of gestational age. The pregnancy was unremarkable except for mild polyhydramnios developing a few weeks before delivery. The initial physical exam was notable for obvious stigmata of Down's syndrome and a purpuric macular rash on the neonate's back, which resolved over the first 6 weeks of life. Chemistry studies on the second postnatal day showed the following: albumin, 3.2 g/dL; alkaline phosphatase, 291 IU/L; total bilirubin, 25.1 m g / d L ; direct bilirubin, 2.0 m g / d L ; AST, 114 IU/L; ALT, 480 IU/L; LDH, 3,420 IU/L; and GGTP, 7 IU/L. The hyperbilirubinemia peaked the following day at 25.8 but responded well to phototherapy which was required for 6 days.
Hematologic Findings The complete blood count (CBC) on the first postnatal day showed the following: WBC, 151.6 × 10e/L; RBC, 3.60 × 1012/L; hemoblogin (HGB), 13.8 g/dL; hematocrit (HCT), From Pathology Associates, Inc, RS., and Sacred Heart Medical Center, Spokane, WA; and Bonner General Hospital, Sandpoint, ID. Address correspondence and reprint requests to Michael de Tar, MD, Pathology Associates Inc, ES., 11604 East Indiana Ave, Spokane, WA 99206. Copyright © 2000 by W.B. Saunders Company 0046-8177/00/3103-0021510.00/0 doi: I0.1053/hp.2000.5206
396
Placental Findings The placenta was examined according to standard protocol. After trimming of membranes and removal of the umbilical cord, The formalin-fixed placenta weighed 572 g and showed apparent meconium staining. The trivascular umbilical cord and villous parenchyma were grossly unremarkable. Microscopically, the placenta was free of inflammation, although the vessels of the umbilical cord and chorionic plate contained numerous blasts and a moderate erythroblastosis. Occasional aggregates were attached to the endothelial lining of the vessels within villous trunks and showed early organizing thrombus formation (Fig 1). The chorionic villi showed early third trimester maturation patterns with abnormally increased numbers of more rounded, bulky villous forms and an associated, generalized villous hypervascularity consistent with "chorangiosis" (Fig 2). The villous stroma did not show tissue infiltration by primitive blast forms, nor was there evidence of chronic villitis. A few larger vessels of the chorionic plate showed a circumferential pattern of endothelial and subendothelial margination of primitive cells (Fig 3). Focal, early vascular wall invasion with associated fibrinoid necrosis of the intima was present within a few of these vessels. These areas also showed an associated apoptosis of primitive cells (Fig 4). This finding was only focally identified in just 2 of the multiple sections examined.
CASE STUDIES
FIGURE 1. Intravascular organizing thrombus containing blasts. (Original magnification × 100.)
FIGURE 3. Circumferential pattern of early vascular wall invasion. (Original magnification x50.)
DISCUSSION True congenital leukemia (TCL) is a rare pediatric malignancy representing less than 1% of all pediatric leukemias. 4 Approximately 200 cases have been reported, with a n u m b e r of these likely representing the more indolent and benign transient myeloproliferative disease of infancy.5 The clinical criteria for a diagnosis of TCL traditionally have included: (1) manifestations during the first 4 to 6 weeks of life; (2) proliferation of immature myeloid, lymphoid, or erythroid cells; (3) infiltration of these cells into nonhematopoetic tissues; and (4) absence of other diseases of differential diagnostic importance, such as erythroblastosis fetalis and congenital infections.6 Distinction of TMD from TCL on the basis of morphological parameters alone is difficult. In both abnormalities, the peripheral blood is characterized by a markedly elevated WBC count with numerous blasts present. Infants affected by TCL are generally in poor clinical condition at presentation, and the prognosis is poor. 5'7,s Pronounced hepatosplenomegaly is common in TCL. Autopsy studies on stillborns show evidence of significant tissue infiltration by leukemic cells. Involvement of the skin by leukemic infiltrates is commonly seen in TCL, occurring in up to 30% to 50% of cases. 9,1° The clinical appearance of the skin lesions in the classic case of TCL is of multiple red-blue nodules with a generalized pattern of
distribution ("blueberry muffin lesions"), although papular and macular lesions have also been described. 9 Neonates with TMD are generally healthier clinically, only rarely show skin involvement, and show only mild to moderate degrees of hepato-splenomegaly. Classic "blueberrymuffin" lesions have not been described in TMD, although erythematous plaques and rashes have. 1° The peripheral blood abnormalities generally resolve within weeks to months, although recurrences with spontaneous remissions have been reported. While the prognosis for TMD is generally good, up to 25% of these patients will develop a true leukenlia, usually within the first 3 years of life. 11,12 Many of these leukemias are of the megakaryoblastic lineage (FAB-M7), which is the most common form of leukemia that develops in children with DS. 12 The placenta is a rare site of neoplastic involvement by fetal malignancy, and metastatic neuroblastoma is the most common congenital tumor to spread to this site. a3The pattern of involvement in metastatic neuroblastoma is primarily intravascular, with the fetal vessels of the umbilical cord, chorionic plate, and chorionic villi showing distention by malignant cells. There are only a few reports describing the pathological findings of TCL within the placenta. 8,1~The placenta typically will show massive chorionic tissue infiltration by blast cells, although a well documented case of fatal TCL showed only an intravascular distribution of these cells. The corresponding
FIGURE 2. Chorangiotic villi with intravascular blasts. (Original magnification x200.)
FIGURE 4. Subendothelial aggregates of blasts with apoptotic cells. (Original magnification x 1000.)
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HUMAN PATHOLOGY
Volume 31, No. 3 (March 2000)
fetal visceral o r g a n s in this case s h o w e d massive infiltration by blastic cells. 8 T h e p l a c e n t a l findings o f T M D have not, to o u r knowledge, b e e n previously described. T h e p l a c e n t a was s o m e w h a t e n l a r g e d for gestational age, a c o m m o n f i n d i n g in t h i r d t r i m e s t e r placentas of DS infants. Erythroblastosis has b e e n d e s c r i b e d in p l a c e n t a s of n e o n a t e s with DS. A similar p a t t e r n o f a b n o r m a l i t y may b e s e e n in t h o s e c o n d i t i o n s associated with fetal-based red-cell destructive processes o r survival defects ( i m m u n e m e d i a t e d hemolysis, glucose-6-phosphorylase deficiency, parvovirus infection, etc.). Differential diagnostic c o n s i d e r a t i o n s o f t h e p l a c e n t a l a b n o r m a l i t i e s in t h e a b s e n c e o f clinical h i s t o r y i n c l u d e a non-specific l e u k o e r y t h r o b l a s t i c reaction, metastasis f r o m a solid fetal malignancy, a n d TCL. T h e significance of early tissue infiltration in t h e p r e s e n t case is u n k n o w n a n d n e e d s f u r t h e r study. Massive tissue infiltration o f n o n - h e m a t o p o e t i c tissues by neoplastic cells is a characteristic finding in fetal tissue of TCL. T h e placenta is a n ideal organ to evaluate for this diagnostic finding b u t is unfortunately only rarely examined. T h e issue of w h e t h e r early tissue infiltration indicates a greater risk for the d e v e l o p m e n t of a true leukemia needs to be addressed. Additional studies o n r o u t i n e l y collected p l a c e n t a s f r o m pregn a n c i e s c o m p l i c a t e d by t r a n s i e n t myeoloproliferative disease are n e e d e d . T h e p a t h o l o g i c a l e x a m i n a t i o n o f all placentas f r o m p r e g n a n c i e s associated with trisomy 21 is r e c o m mended.
REFERENCES 1. Weinberg AG, Schiller G, Windmiller J: Neonatal leukemoid reaction. An isolated manifestationof mosaic trisomy21. AmJ Dis Child 136:810-311, 1982 2. Ridgway D, Benda GI, Magenis E, et al: Transient myeloproliferative disorder of the Down type in the normal newborn. AmJ Dis Child 144:11171119, 1990 3. McCoyJP, Overton WR: Immunophenotyping of congenital leukemia. Cytometry 22:85-88, 1995 4. Pavlucci G, Rosito P: Neonatal myeloproliferative disorders in Dowlr's syndrome and congenital Ieukemias. Hematalogica 72:121-125, 1987 (suppl) 5. Fong C, Brodeur G: Down's Syndrome and Leukemia: Epidemiology, genetics, cytogenetics and mechanisms of leukemogenesis. Cancer Genet Cytogenet 28:55-76, 1987 6. Heikinheimo N, Pakkala S,Juvonen E, et al: Immuno- and cytochemical characterization of congenital leukemia: A case report. Med Pediatr Oncol 22:279-282, 1994 7. McCoyJE Travis S, Blumstein L, et al: Congenital Leukemia: Report of two cases. Cytometry 22:89-92, 1995 8. Gray ES, Balch NJ, Kohler H, et ah Congenital leukemia: An unusual cause of stillbirth. Arch Dis Child 61:1001-1006, 1986 9. Resnick KS, Brod BB: Leukemia cutis in congenital leukemia. Analysis and review of the world literature with report of an additional case. Arch Dermatol 129:1301-1306, 1993 10. Pierce MI: Leukemia in the newborn infant. J Pediatr 54:691-706, 1959 11. Bhatt S, Schreck R, Graham J, et al: Transient Leukemia with Trisomy 21: Description of a case and review of the literature. Am J Med Genet 58:310-314, 1995 12. ZipurskyA, Peeters M, Poon A: Megakaryoblasticleukemia and Down's syndrome: A review. Pediatr Hematol Oncol 4:211-230, 1987 13. Las Heras J, Leal G, Haust D: Congenital leukemia with placental involvement. Cancer 58:2278-2281, 1986
UTERINE MYXOID LEIOMYOSARCOMA WITHIN A LEIOMYOMA KHUSH MITTAL, MD, DOROTA POPIOLEK, MD, AND RITA I. DEMOPOULOS, MD
A case of myxoid leiomyosarcoma of the uterus arising in a leiomyoma is reported. Although the tumor showed very low mitotic activity ranging from zero to 2/10 HPF, the presence of infiltrative pattern of growth and a high MIB-1 index (60% of cells positive)
established the diagnosis. Myxoid leiomyosarcoma may arise in leiomyoma. HUM PATHOL 31:398-400. Copyright © 2000 by W.B. Saunders Company Key words: leiomyoma, myxoid, leiomyosarcoma, uterus, MIB-1.
Myxoid l e i o m y o s a r c o m a o f t h e u t e r u s is a rare n e o p l a s m with only 12 cases r e p o r t e d to date. 1-6 We r e p o r t a case o f m y x o i d l e i o m y o s a r c o m a arising in a leiomyoma. T h e case is b e i n g r e p o r t e d for 3 reasons: (1) to p o i n t o u t t h a t a leiomyos a r c o m a may arise in a leiomyoma; (2) to e m p h a s i z e t h e i m p o r t a n c e o f i n c l u d i n g l e i o m y o s a r c o m a in differential diagnosis o f l e i o m y o m a s with m y x o i d a p p e a r a n c e ; a n d (3) to illustrate t h e fact t h a t a l t h o u g h s o m e m y x o i d leiomyosarcomas have a low mitotic c o u n t , t h e overall proliferative activity as i n d i c a t e d by MIB-1 e x p r e s s i o n may b e high.
cystic t u m o r e x t e n d i n g into t h e m i d - a b d o m e n with displacem e n t o f t h e u t e r u s to t h e left. T h e clinical differential diagnosis was ovarian n e o p l a s m versus leiomyosarcoma. T h e CA 125 s e r u m level was 11. P r e o p e r a t i v e e n d o m e t r i a l biopsy failed to o b t a i n e n d o m e t r i a l tissue. At s u r g e r y a large (30 cm)
CASE R E P O R T A 73-year-old m u l t i p a r o u s w o m a n (G4P3013) whose m e n o p a u s e o c c u r r e d at age o f 50 p r e s e n t e d with 30-1b w e i g h t loss over 1 year a n d i n c r e a s i n g a b d o m i n a l g i r t h for 2 m o n t h s . C o m p u t e d t o m o g r a p h y scan s h o w e d mostly solid a n d partially
From the New York University School of Medicine and Kaplan Cancer Center, NewYork, NY. This work was supported in part by Kaplan Cancer Center Grant No. P30 CA16087. Address correspondence and reprint requests to Khush Mittal, MD, Department of Pathology, 4W35B, Bellevue Hospital, 27th Street and 1st Avenue, NewYork, NY 10016. Copyright © 2000 by W.B. Saunders Company
FIGURE I.
Portion of the cut surface of the tumor showing myxoid confluent nodules of leiomyosarcoma (larger arrow) surrounded by leiomyoma (smaller arrow).
0046-8177/00/3103-0022510.00/0 doi: 10.1053/hp.2000.5207
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