mjiri.iums.ac.irmjiri.iums.ac.ir/article-1-1225-en.pdf · % &sN $ & *e Ä#/èN N ·JN y N $ ! $ ? ?...
6
Medical Joul of e Islamic Rublic of Iran Vole 10 Number 1 Spg 1375 y 1996 Case Reports MALIGNANT HIS TIOCYTOSIS: A CASE REPORT AND REVIEW OF THE LITERATURE A. BANIHASM, * M.D., T GHIASSI, ** M.D., S. ZABIHYAN, M.D. From the Departments of*Pedtrics and **Pathogy, Ghaem Hospital, Mashhad Universi of Medal Sciences, Mashhad, Ismic Replic of Ir. ABSTRACT Malignant histiocytosis (MH) is a rare hematologic malignancy, especially in the first decade of life. The disease is clinically characterized by fever, hepatosplenomegaly, lymphadenopathy, pancytopenia and jaundice, and histologically by systemic proliferation of malignant histiocytes and hemophagocytosis. The prognosis is poor and often the diagnosis is not made before death. Because of the rity of this disease, it is unusual for practitioners to diagnose it by bone marrow aspation (BMA) alone. M, Vol.1D, No.1, 79-83,1996. INTRODUCTION was inuced in 1966 by Rapport, although this disease was originally descrid in 1936 b y Scott and Robb- Smith under the name of histiocytic medullary reticulosis. The disease is classified as class III of the histiocytosis syndrome4•19 and is a re, nonfilial, ridly progressive and fat neoplasm of ue histiocytes that affects children and adultsl2•19 with a mean age of 31 yes. I S accounts for less 10% of hematoietic malignancies with an average of one case per ye.6 The male to female rao is 2.21IL it may associated with primy mediasnal germ cell tumors i n males.IO CASE REPORT A 5 year old girl was referred to our hospital with fever and ee pain of 2 days' duraon and constipation. On * Assistant Professor of Pediaics, Deptment of Pediaics, Ghæm Hospit, Mhh University of Medical Sciences. ** Assistant Professor of Pathology, Deptment of Pathology, Ghæm Hospit, Mhh University of Medical Sciences. 79 admission there were no abnorm physical findings except fever ( tempe38.5°C) and limping. Her general appece was go. Routine laboratory examinations revealed only md normyc, normochromic anemia (Hct= 33%), abnormal ESR (110 mm/h) and a sitive C. During e hospital stay arthralgia subsided, and l other examinaons and cultures were negave. Radiography of the ees showed leukemic anslucent lines. The pepheral blood smear was normal. Bone mw aspiraon was performed and reported as acute undifferentiated leukemia. Her parents refused chemotherapy. 5 months later, she developed hepatosplenomegaly, massive cervical lymphadenopathy and inaorbital soſt ssue swelling and echymoses. Trismus had been present for 1 month and aominal pain for 2 weeks. Her general condition deterior- ated and there was weaess and wasng. Laratory fmdings summarized in Table 1. The second BMA was reported as ALL(L3)' d the patient was eated by the standard ALL protocol. At the end of inducon of remission she was admitted for the 3rd lime with inctable bleeding om buccal ulcers, abdominal pain, diarrhea and melena Upon physical examination she was very l with severe weight loss and cachexia. Cervical Downloaded from mjiri.iums.ac.ir at 7:22 IRST on Sunday October 25th 2020
Transcript of mjiri.iums.ac.irmjiri.iums.ac.ir/article-1-1225-en.pdf · % &sN $ & *e Ä#/èN N ·JN y N $ ! $ ? ?...
Medical Journal of the Islamic Republic of Iran
Volume 10 Number 1
Spring 1375 May 1996
Case Reports
MALIGNANT HISTIOCYTOSIS: A CASE REPORT
AND REVIEW OF THE LITERATURE
A. BANIHASHEM, * M.D., T. GHIASSI, ** M.D., AND S. ZABIHYAN,
M.D.
From the Departments of*Pediatrics and **Pathology, Ghaem Hospital, Mashhad University of
Medical Sciences, Mashhad, Islamic Republic of Iran.
ABSTRACT
Malignant histiocytosis (MH) is a rare hematologic malignancy, especially in the first decade of life. The disease is clinically characterized by fever,
hepatosplenomegaly, lymphadenopathy, pancytopenia and jaundice, and histologically by systemic proliferation of malignant histiocytes and
hemophagocytosis. The prognosis is poor and often the diagnosis is not made
before death. Because of the rarity of this disease, it is unusual for practitioners to diagnose it by bone marrow aspiration (BMA) alone.
MJIRI, Vol.1D, No.1, 79-83,1996.
INTRODUCTION
MH was introduced in 1966 by Rappaport, although this disease was originally described in 1936 by Scott and RobbSmith under the name of histiocytic medullary reticulosis.
The disease is classified as class III of the histiocytosis syndrome4•19 and is a rare, nonfarnilial, rapidly progressive and fatal neoplasm of true histiocytes that affects children and adultsl2•19 with a mean age of 31 years. IS It accounts for less than 10% of hematopoietic malignancies with an average of one case per year.6 The male to female ratio is 2.21ILand it may be associated with primary mediastinal germ cell tumors in males.IO
CASE REPORT
A 5 year old girl was referred to our hospital with fever and knee pain of 2 days' duration and constipation. On
* Assistant Professor of Pediatrics, Department of Pediatrics, Ghaem Hospital, Mashhad University of Medical Sciences. ** Assistant Professor of Pathology, Department of Pathology, Ghaem Hospital, Mashhad University of Medical Sciences.
79
admission there were no abnormal physical findings except fever (axillary temperature=38.5°C) and limping. Her general appearance was good. Routine laboratory examinations revealed only mild normocytic, normochromic anemia (Hct= 33%), abnormal ESR (110 mm/h) and a positive CRP.
During the hospital stay arthralgia subsided, and all other examinations and cultures were negative. Radiography of the knees showed leukemic translucent lines. The peripheral blood smear was normal. Bone marrow aspiration was performed and reported as acute undifferentiated leukemia.
Her parents refused chemotherapy. 5 months later, she developed hepatosplenomegaly, massive cervical lymphadenopathy and infraorbital soft tissue swelling and echymoses. Trismus had been present for 1 month and abdominal pain for 2 weeks. Her general condition deteriorated and there was weakness and wasting. Laboratory fmdings are summarized in Table 1.
The second BMA was reported as ALL(L3)' and the patient was treated by the standard ALL protocol. At the end of induction of remission she was admitted for the 3rd lime with intractable bleeding from buccal ulcers, abdominal pain, diarrhea and melena Upon physical examination she was very ill with severe weight loss and cachexia. Cervical
Dow
nloa
ded
from
mjir
i.ium
s.ac
.ir a
t 7:2
2 IR
ST
on
Sun
day
Oct
ober
25t
h 20
20
Malignant Histiocytosis
Table I. Lab rmdings.
Exam. Normal Range Results
WBCcount 2,300/J,Ll Platelet count 87000/J,LI Hct 27% ESR 87mm/h LDR 100-500 4740U/L Ca 9-11 9.7 mg/dl p 4-7 3.2 mg/dl
Uric acid 2.5-6 9.6 mg/dl Urea 17-50 23 mg/dl Creatinine 0.9-1.6 0.8 mg/dl Reticulocytes 0.1% CSF cytology neg. for malignancy ALP up to 250 117U/L ACP 5-11 8U/L
lymph nodes, liver and spleen were palpable but smaller than before. A surprising finding was ascites and abdominal distention.
BMA and peripheral blood smear indicated no response to treatment, therefore the original aspirate specimens were reviewed and prominent hemophagocytosis with atypical, blast-like histiocytes was noticed (Figs. 1,2,3) which was unappreciated initially. Non-specific esterase staining of the cells was positive, thus the diagnosis of MH was made based on BMA fmdings. The peripheral blood smear showed atypical histiocytes (Fig. 4).
COP AD regimen was used for chemotherapy but on the second -day of therapy, the patient suddenly developed periorbital edema and died. Autopsy was restricted only to needle biopsies of the liver and spleen. The liver specimen was normal but the spleen biopsy was compatible with MH (Figs. 5,6,7).
DISCUSSION
Etiology MH is a nonhereditary disease of unknown etiology.
Although aneuploidy and some complex chromosomal abnormalities have been reported [t (8: 16) (Pll, p13) and t(5:6) (5q3S:6 p21)), there i s no significant genetic abnormality.5 .8.17,19
Clinical manifestations
Fever, localized or generalized frequently tender lymphadenopathy and weakness are the most common initial presentations. 18,19 Hepatosplenomegaly, skin lesions, back, chest and abdominal pain, sweating and a soft tissue mass are also frequent findings.5,6,12.13.17.19 Jaundice is seen later in the course of disease.6,12.13.17,19
Skin lesions are often nonpruritic, macular, erythematous
80
Fig. 1. Bone marrow aspiration (magnification X 10).
Fig. 2. Bone marrow aspirate with atypical histiocytes and hemophagocytosis (magnification x 40).
Fig. 3. Bone marrow aspirate showing atypical histiocyte
(magnification x 100).
and blanching but may change to raised nodular lesions. 17
Other less frequent presentations include CNS involvement with positive CSF cytology, respiratory symptoms, GI symptoms (GI bleeding & diarrhea), buccal ulceration and
Dow
nloa
ded
from
mjir
i.ium
s.ac
.ir a
t 7:2
2 IR
ST
on
Sun
day
Oct
ober
25t
h 20
20
A. Banihashem, M.D., et al.
Fig. 4. Peripheral blood smear revealing an atypical histiocyte.
Fig. 5. Spleen (H&E stain, magnification x 5).
'�. ""'l'.""' ''''_-.. 6. Spleen showing atypical histiocytes
magnification x 10 ).
pleural effusion.6.17.19 Bone lesions I 1,13 and ascitesl9 are also rarely reported. The lung is the most common site of extranodal involvemenLI7
81
Fig. 7. Spleen showing atypical histiocytes (H&E stain,
magnification x 40).
Laboratory findings
Hematologic: Anemia is the most frequent finding (75%) followed by thrombocytopenia (58%), leukopenia and pancytopenia (21 %).14.17.19 Coombs' positive hemolytic anemia, thrombocytosis, leukocytosis, monocytosis, circulating histiocytes and fibrinopenia are infrequent fmdings.6,14,18
Biochemical: Liver enzymes are often increased, especially LDH (33%).17.19 Serum bilirubin levels above 2 m g/dl are p resent in about 29% of patient s.17 Hypoalbuminemia, hyponatremia «130 mEq/L) and hyper uricemia are other infrequent findings.6,17 Hypenerritinemia may be a significant indicator of MH.ls
Radiologic: Abnormal CXR has been reported in 33% of cases, although overt respiratory symptoms are rare.17 CXR fmdings include pleural effusion, hilar adenopathy and reticular patterns.6 Periosteal reactions and translucent zones have rarely been reported.16
Immunology and immunohistochemistry: Positive RF, increased IgA and polycJonal hypergammaglobulinopathy have been reported by some authors.6 Histiocytes react with alphanaphtyl esterase and acid phosphatase and are inhibited by NaP and tartarate, respectively.9. 16.17,1 9 Sudanophilia, PAS positivity and free iron staining which probably arise largely from phagocytic activity are also increased.9 The malignant cells also react with alpha antichymotripsin and antibodies directed against EMA, HLA-DR antigens, CD 25, CD 30, CD 68, CD 71,14 and S-l00 protein.s.ls There are neither B- nor T-cell antigens.14 The degree of cytologic atypia and phagocytic activity is indirectly related to the quantity of lysozyme within the cells.13
Diagnosis Diagnosis is based on biopsy and erythrophagocytosis
in the bone marrow, Ii ver and spleen and histiocyte infiltration
Dow
nloa
ded
from
mjir
i.ium
s.ac
.ir a
t 7:2
2 IR
ST
on
Sun
day
Oct
ober
25t
h 20
20
Malignant Histiocytosis
Table II. Complementary lab examinations.
Exam.· Normal Range Results
/ 16L
WBC 1500 (JJP \6M 18B
Hct 24% Platelets 12000/J.Ll I ESR 20mm/h Coombs' test negative Total bilirubin 0.3-1 0.86 mgJdl D. bilirubin 0.1-0.4 0.25 mgJdl Ind. bilirubin 0.1-0.6 0.61 mgJdl S. ferritin 200 900 Triglycerides 400 Cholesterol 1 36 CXR nonnal SchUller rad. nonnal Brain CT scan mild brain atrophy LDH 120-300 3/20U/L CSF cytology negative
TII* 20.8% B* 4 4.2
* analysis of an:a with high possibility of tumoral cells.
of subcapsular and medullary regions of lymph nodes, splenic red pulp or hepatic sinusoids.4,5.12.t7.18 Although phagocytosis is essential for the diagnosis of MH, phagocytosis may notbehistologically evident in all caseS.13. 18 and may often be seen in benign-looking histiocytes.19
Plasma cells are increased in 78% of cases. 17 Skin,lung, CNS, pericardium, bone, soft tissue, intestinal tract and meninges are other frequent sites of inflltration.4. 6.17 Nasal and paranasal sinuses and the kidney are rare sites of involvement in MH.6.17
Malignant cells are atypical with deep blue cytoplasm, high cytoplasmic/nuclear ratios. prominent nucleoli and frequent mitoses. Cellular atypia increases with time.18.19
Bone marrow biopsy is positive in 27% of cases and bone marrow aspiration in 33%;17 therefore BMA is more diagnostic than BMB.
Differential diagnosis MH must be differentiated clinically and histologically
from undifferentiated c arcinoma, non-Hodgkin's lymphoma, Hodgkin's diseas e , infection induced hemophagocytic syndrome, hemophagocytic lymphohistiocytosis, T-cell lymphoma, AML, histiocytosis X, sinus histiocytosis with massive lymphadenopathy, hairy cell leukemia and myeloproliferative disease.6.7.13.16.19
Treatment Multi-agent chemotherapy with cyclophosphamide,
82
doxorubicin, vincristine, prednisolone or etoposide and cytosine arabinoside may improve survival.2.14
Some effective regimens which have been used with relatively good results include COPAn, ACOP, CHOP, CVP and BACOP.1.6.12.16.17
CNS prophylaxis may be done but its effectiveness is controversial.I.12.17 Autologous bone marrow transplantation has been reported with good results. 3
Outcome
MH is a rapidly progressive and fatal malignancy; only a few cases of long-term survival have been reported. 6Most patients die within a year of disease.19 In one series the median survival was 4 months with a maximum duration of 25 months. 6Hepatic and pulmonary dysfunction6 and platelet counts < 150000 at presentation indicate a poor prognosisY
The dose of drug delivered is another important prognostic factor.17 Age, sex, stage and site of disease, WBC count and LDH and bilirubin levels do not seem to be important in outcome.6
Overall mortality rate is 68 %5 and all untreated patients die within weeks to months.16.19Common causes of death are cerebral hemorrhage and pneumonia.6
REFERENCES
1. Alexander M, Daniels JR: Chemotherapy of malignant histiocytosis in adults. Cancer 39: 1011-17, 1977.
2. Bertino R, et al: Malignant histiocytosis, response to VP-16-213 and cytosine arabinoside. Cancer 54: 991-3, 1984.
3. Cazin B, et al: Successful autologous bone marrow transplantation in second remission of malignant histiocytosis. Bone Marrow Transplant 5 (6): 431-3,1990 (Abst).
4. Chu T, et al: Histiocytosis syndrome in children by writing group of histiocyte society. Lancet 1: 208-9, 1987.
5. Davita VT: Lymphocytic Lymphoma. In: Devita VT, et al (eds), Cancer, Principles and Praetice of Oncology, Philadetphia: I. B. Lippin Cott Co, pp. 1759-61, 1989.
6. Esselitine DW: Malignant histiocytosis. Cancer 52: 1904-10, 1983.
7. Favara BE: Hemophagocytic lymphohistiocytosis. Semin Diagn Pathol 9 (1): 63-74, 1992 (Abst).
8. Gogusev I, etal: Genotype markers & proto-oncogene analysis in CD 30 positive malignant histiocytosis. Int I Cancer 46 (1): 106-12. 1990 (Abst).
9. Hagho FGJ: Major cytochemical and histochemical findings in lymphocyte subpopulations. In: Hematological Cytochemistry. 2nd edition, U.K., Churchill Livingstone, p. 469, 1988.
10. Kee CH, et al: True histiocytic malignancy associated with a malignant teratoma in a patientwith46 XY gonadal dysgenesis. Am I Surg Pathol 16 (2): 175-83, 1992 (Abst).
11. Kozlowski K, et al: Rare primary iliac, pubic and ischial tumor in children. Austral Radiol 33 (4): 361-8, 1989 (Abst).
12. Lanzkowsky P: Histiocytosis syndromes. In: Lanzkowsky P (cd.), Manual of Pediatric Hematology & Oncology. Edinburgh, Churchill Livingstone, pp. 370-3, 1989.
Dow
nloa
ded
from
mjir
i.ium
s.ac
.ir a
t 7:2
2 IR
ST
on
Sun
day
Oct
ober
25t
h 20
20
A. Banihashem, M.D., et al.
13. Mendelsohn G, et al: Relationship of lysozyme to histiocytic differentiation in malignant histiocytosis. Cancer 45: 273-9, 1980.
14. Nezelof G , et al: Malignant histiocytosis in children. Sem in Diagn Pathol9 (1 ): 75- 89 , 1992 (Abst).
15. Okaro M, et al: Hyperferritinemia as a significant indicator s uggesting malignant histiocytosis. Br J Hematol72 ( 3 ): 473-
4,1989. 16. SchoutenJ, etal: Malignanthistiocytosis, clinical & cytogenetic
83
studies in a newborn & a child. Cancer 52 : 1226 -36, 198 3 .
17 . Tserg A , et al: Treatment of malignant histiocytosis. Blood 64 (1); 45-53, 1984.
18 . WarnkeRA, eta!: Malignant histiocytosis. Cancer 35: 215-30, 1975.
19. Komp MD; Inflammatory and malignant histiocytosis, In: Williams JW (ed), Hematology. New York: MCGraw-Hill pp. 899 -900, 1990.
Dow
nloa
ded
from
mjir
i.ium
s.ac
.ir a
t 7:2
2 IR
ST
on
Sun
day
Oct
ober
25t
h 20
20
Discover the wide world of Islamic literature
The journal is produced to a very high standard, and should be a very useful source
for all libraries and information users concerned with Islamic issues.
Information Development (London), Volume 7, Numbcr 4, pages 241·242
This journal is doing a singular service to the cause of the publicity of periodical
litemt1tre on Islamic culture and civilization in all its diverse aspects. Every scholar
of Islamic Studies should feel indebted to you for this service.
PROFESSOR S.M. RAZAULLAH ANSARI President, Internationa[ Ul1lon of History and Philosophy of Science (IUHPS)
Commission for Science and Technolo,gy in lslamic Civili:atitm, Ne\v Delhi, India
(Periodic, Islamica is) an invaluable guide ...
PROFESSOR BILL KATZ Lihrar�JO!mwl (New York), Volume 118, Number 21, page 184
Periodica IsIamica is a most valuable addition to our reference collection,
PROFESSOR WOLFCANC BEHN Union Catalogue of Islamic Publications, Swatsbibliothek rreussischer Kulturhesitz
Berlin, Gcrml:1ny
It is recommended for all research libraries and scholars of the Islamic viewpoint.
DR. RICHARD R CENTINC M,,/riC,,/wra/ Rel'ielL' (Wesrport, ConncHicut), Volume 2, Numher I, page 40
You should be congratulated on Periodica lslamica which should prove to be a
valuable journal to /Jersom interested in Islam and the entire Muslim World.
AMFlASSADOR (RTD.) CHRISTOPHER VAN HOLLEN The Middle East Institute, Washington DC, USA
Periodica Is/a mica is an international contents journal. In its quarterly issues it reproduces tahles of contents from ,1 wide variety of serials, periodicals and other recurring publications worldwide. These primary puhlications are selected for indexing by Periodica Is/amica on the basis of their significance ior religious, cultural, socioeconomic ,lIld political affairs of the Muslim world.
Periodica Is/amica is the premiere source of reference for all multi-disciplinary discourses on the world of Is[am. Browsing through an issue of Periodica Is/amica is like visiting your library 100 times over. Four times ,1 year, in a highiy compact format, it delivers indispensable information on a broad spectrum of disciplines exp[icitly or imp[icitly related to Islamic issues.
If you want to know the Muslim world better, you need to know Periodica Islamica better.
� Editor-in·Chier 0 Dr. Munall'ar A. Ances
Consulting Editor 0 Zarar Abbas Malik Periodica Islamica, 22 Jalan Uku
Kuala Lumpur·59100, Malaysia
America Onlille • dranees CompuSme.72260.227
Delphi. drmanees IlIterNet. dranees@klc),ber.pc.my
P E RIO D[CA
ISLAMICA ',.11...,.-1 i.Jij.'.'.'. k-,Hij .• ,.*,.iiW.' .i4
Subscription Order ForIll Annual Subscription Rates
o Individual US$40.00 0 Institution US$249.00
Name _____ _____________ ________________ __________ ______________ ________________ _ _ ____ _
Address __________________________________________ _______ ____ _____________ __________ ___
City, State, Code Country ________ _
o Bank draft
o acoupons
o Money order
011]
0_ O[Z]
BY 1 � 1 To place your order
PHONE QlD immediately telephone (+60·31 282-5286
0000-0000-0000-0000 Expiration date _____________________________ _
Signature------------------------
BY II'lI...II To fax your order lilli complete this order
FAX form and send to (+60-3) 282-1605
BY 1 �I Mail this compteted
� order form to MAIL Periodica Islamica
Berita Publishing
SUBSCRIBERS IN MALA.YSIA MAY PAY AN EQUIVALENT AMOUNT IN RINGGIT IMS) AT THE PREVAILING EXCHANGE RATE
Subscribe Now! Subscribe Now! Subscribe Now! Subscribe Now!
Dow
nloa
ded
from
mjir
i.ium
s.ac
.ir a
t 7:2
2 IR
ST
on
Sun
day
Oct
ober
25t
h 20
20
![T-TF—N- …P-RÈ-G‰]Ã-CK‰ -UXÍN-F‰c-q-T-T[÷Cc-cÈ,, · GÈc-≠ÈN ii The Treasury Of Jewelswas compiled and edited by Khenchen Palden Sherab Rinpoche.In this second, revised](https://static.fdocuments.in/doc/165x107/5c0a869709d3f23c1a8ba07e/t-tfn-p-re-ga-ck-uxin-fc-q-t-tcc-ce-gec-en-ii-the.jpg)
![[ lâ^]åz ^ú ¾W0e¹~ÆR Oá`oQl mO ÈN u( - zj.gov.cn](https://static.fdocuments.in/doc/165x107/61c56f650f69c34e676a7b83/-lz-w0er-ooql-mo-n-u-zjgovcn.jpg)
![Untitled-6 [] · PSIHOMOTRICITATE MANAGEMENT IN SÄNÄTATE RECUPERARE APARATURÄ ECHIPAMENTE ÈN 12 RECUPERARE $1 MODELARE CORPORALÄ Tot81 ore optionale pe säptämânä RECAPITULATE](https://static.fdocuments.in/doc/165x107/5e054277032133497f13f5af/untitled-6-psihomotricitate-management-in-sntate-recuperare-aparatur-echipamente.jpg)
![Major NHS Organisation Aspyre Case Study...ÈN\ nXek\[ kf dXb\ k_\ jpjk\d m\ip \Xjp kf lj\ Xj dXep f] k_\ k\Xd _X[ c`kkc\ fi ef gifa\Zk dXeX^\d\ek \og\i`\eZ\ Xe[ n\i\ le]Xd`c`Xi n`k_](https://static.fdocuments.in/doc/165x107/601778608f9a3c39d2617a42/major-nhs-organisation-aspyre-case-study-n-nxek-kf-dxb-k-jpjkd-mip.jpg)
