CASE REPORTS

Blood, Vol. 55, No. 2 (February), 1980 253

“Microgranular” Acute Promyelocytic Leukemia: A Distinct

Clinical, Ultrastructural, and Cytogenetic Entity

By Harvey M. Golomb, Janet D. Rowley, James W. Vardiman, Joseph R. TeSta, and Ann Butler

Three patients with acute leukemia, disseminated intravascular coagulation, and a specific acquired chromosome

abnormality [t (1 5;1 7)] were found by transmission electron microscopy to have the typical distribution of granules seen in

promyelocytes. However, the average granule sizes were 1 20. 1 70, and 1 80 nm, respectively, for the three patients,

significantly less than the 250-nm resolution of light microscopy. We regard the leukemia in these three patients as

comprising a distinct clinical, ultrastructural, and cytogenetic entity that we have chosen to call � ‘microgranular’ acute

promyelocytic leukemia.

A CCORDING to the criteria of the French-Amen-

can-British (FAB) cooperative study group, the

diagnosis of acute promyelocytic leukemia (APL)

should be made only when the “great majority” of

cells are abnormal promyelocytes whose cytoplasm is

packed with coarse granules and which have promi-

nent Auer-like bodies. Clinically, APL is a form of

acute leukemia characterized by episodes of hemor-

rhage and by disseminated intravascular coagulation

(DIC).2 Cytogenetically, a specific chromosome

abnormality [t (15;I7)J has been identified in patients

with APL;35 this translocation has not been reported

in any of the other acute leukemias of the FAB

classi fication 6

In 1978, we reported on a patient whose bone

marrow appeared, by light microscopy, to be similar

morphologically to that in acute mycloblastic

leukemia with maturation. In addition to DIC, the

patient was found on cytogenetic analysis to have the

I 5; 17 translocation. The characteristic distribution

and morphology of granules seen in APL were

observed only when transmission electron microscopy

(TEM) was used.7 More recently, in reviewing our

experience from 1973 to l’i18,� we briefly alluded to a

similar case. The present report was prompted by a

third identical patient who was first examined in early

1979. We now describe in detail three patients with

DIC, a t(l5;l7), and a typical distribution of granules

in promyelocytes, which, in most cells, could be

observed only with TEM.

MATERIALS AND METHODS

Wright-stained peripheral blood (PB) and bone marrow (BM)

aspirates obtained from the 3 patients were examined, and 500-cell

differential counts were done. The PB and BM specimens were

studies with peroxidase, periodic acid-Schifi, a-naphthyl acetate

esterase (ANAE) with and without sodium fluoride, a-naphthyl

butyrate, naphthol AS-D-chloroacetate esterase, and acid phospha-

tase reactions.

Spicules from BM aspirates were prepared for TEM by conven-

tional methods. Preparation and analysis of chromosomes from BM

and PB were as previously described.9 All samples were analyzed

with Q banding.tm#{176}G banding” and reverse (R) banding’2 were each

used in the analysis of one sample from patient I to allow precise

identification of the I 5; 17 rearrangement.

Case 1

A detailed case report was presented previously.1

Case 2

The patient, a 27-yr-old black woman, was admitted to the

Obstetrics Service in June 1978, at approximately 15 wk into her

first pregnancy, because of bleeding gums and hematuria. One week

prior to admission, the patient experienced dull lower abdominal

pain that caused fl() distress. At the same time, she had bleeding

gums. She saw her dentist, who cleaned her teeth and started her on

penicillin tablets. Her gums continued to be painful, and I day prior

to admission she noticed blood-tinged urine. On the day of admis-

sion. gross hematuria had developed. The patient also had bruised

easily for several days, but she denied having rectal or vaginal

bleeding. No fever or cough was present. The past medical history

included a previous admission 5 yr earlier for repair of an umbilical

hernia.

Physical examination revealed a blood pressure of I 20/60 mm

Hg. a regular pulse of 90/mm, and regular respirations of I 6/mm;

the patient was afebrile, The skin contained multiple ecchymoses.

The ocular fundi showed no evidence of hemorrhage or exudate. The

gums were swollen and bleeding and were covered with petechiae.

The chest was clear, and the abdomen was protuberant without a

palpable liver or spleen. The findings in the remainder of the

examination were unremarkable; no localized neurologic signs were

discovered.

The initial laboratory examination revealed a white blood cell

(WBC) count of 10.9 x 109/liter with l7 bands. 5� lymphocytes,

4% monocytes, and 9#{216}(3�,myeloblasts. The hematocrit (H) was

29.3% and the platelet count I I x l09/liter. The patient was

immediately transferred to the Hematology Service. Routine chem-

istry laboratory values on the day of admission were within normal

limits. However, the plasma fibrinogen was 0.07 g/liter (normal,

0.1-0.4 g/liter). The prothrombin time (PT) was 20.3 see, with a

control of 12.4 see, and the partial thromboplastin time (PTT) was

From the Departments of Medicine and Pathology, Univer.sitt’ of

(‘hicago, and the Franklin McLean Memorial Research Institute

(operated b�v the University of Chicago for the Department of

Energy under Contract EY-76-C-02-0069), (‘hicago, Ill.

Supported in part by the Hematology Research Foundation, the

Thomas Moore Fund, the Cancer Research Foundation, and Grant

CA lo9lOfrom the National Institutes of Health.

Submitted July 18, 1979; accepted October 10, 1979.

Address reprint requests to Harvey M. Golomb, M.D., Box 420,

950 East 59th Street, Chicago, Ill. 60637.i(� 1980 by Grune & Stratton, Inc.

0006-4971/80/5502-OOl ISOl.00/0

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254 GOLOMB ET AL.

Table 1 . Clinical Characteristics

Survival

Patient

Age(yr) Sex Race Initial Therapy Response

From

Diagnosis

(mo) DIC

PreviouslyReported

(Ref)

1 20 M B Ara-C, TG CR 8 + 7

2 27 F B Ara-C, TG, Daun CR 7 + + 8

3 25 F W Ara-C, TG, Daun PR 2 + + -

M, male; F, female; B. bI ack; W, whit e; Ara-C, cytosine arabinoside; TG, 6 thioguanine; Daun, daunorubicin; CR, complete re sponse; PR, partial

response; DIC. disseminated intravascular coagulation.

38.5 sec with a control of 26.2 sec. Fibrin degradation products

(FDP) were reported between 40 and 80 �g/ml (normal, less than

20 �zg/ml).

The patient was diagnosed as having acute myelogenous or

myelomonocytic leukemia at the time of admission, underwent a

therapeutic abortion, and was begun on chemotherapy I day later.

Chemotherapy consisted of our TAD regime, which included 6-

thioguanine (100 mg/sqm every 12 hr for 5 days), cytosine arabino-

side (200 mg/sqm with continuous 24-hr infusion for 5 days), and

daunorubicin (60 mg/sqm iv. push daily for 3 days). A BM biopsy

done approximately I mo after the initiation of therapy showed a

cellularity of 1 5% with clusters of blasts. A second cycle of chemo-

therapy was started 5 wk after the initial one; at the start the

hematocrit was 27.9%, the WBC count 3.7 x 109/liter, and the

platelet count 200 x l09/Iiter. A BM specimen obtained I mo later

showed residual acute leukemia; at that time, the Hct was 31.9%,

WBC count 22.3 x 109/liter, and the platelet count 367 x lOt/liter.

The patient now refused any further inpatient therapy and was

begun on 6-thioguanine. 40 mg bid., as an outpatient. One month

later, a repeat BM specimen was 80% cellular. No evidence of

residual disease was found; 6-thioguanine was stopped. The patient

developed HAA-positive hepatitis 2 mo later (i.e., 5 mo after her

initial diagnosis and treatment). A BM specimen obtained in

December 1978 appeared normal, with less than 5% blasts. The

patient was placed on maintenance therapy with only hydroxyurea

and BCNU. She was last seen 9 mo after initial diagnosis and

treatment, was doing well, had no complaints, and showed a steady

weight gain. Blood samples at that time showed a WBC count of 5.1

x l09/liter, Hct of 37.9%, and a platelet count of 165 x 109/liter.

Case 3

The patient, a 25-year-old white woman, was in excellent health

and studying at a college in California until approximately 4 days

prior to admission when she noted multiple ecchymoses as well as

petechiae on her thighs and lower legs. About 2 days prior to

admission, she felt feverish without specific complaints. She was

referred to a school physician, who noted a WBC count of 4.35 x

109/liter, Hct of 30.5%, and a platelet count of 14 x l09/liter. The

differential WBC count showed 1% eosinophils, 1% bands, 14%

neutrophils, 83% lymphocytes, and I % monocytes. She was referred

to a hematologist, who obtained a sternal BM aspirate and made a

diagnosis of acute leukemia, probably myeloblastic. She was re-

ferred to the University of Chicago for further evaluation and

therapy.

The patient, who was mildly anxious but in no acute distress,

admitted to a weight loss of approximately 1 5 lb during the previous

6 mo. Her menstrual period approximately 1 wk earlier had been

heavy and longer than usual by 3 days. She had had no epistaxis,

melena, hematemesis, or hematuria, but complained of persistent

oozing from the BM aspiration site in the sternum.

During physical examination, her temperature was 37.8#{176}C,the

pulse 100/mm and regular, respirations 14/mm and regular, and

the blood pressure I 30/80 mm Hg. The patient was slightly pale,

with multiple ecchymoses on her extremities and on her soft palate.

There was oozing from the sternal marrow site. The remainder of

the findings in the examination were unremarkable; no adenopathy,

hepatosplenomegaly, or abnormal neurologic findings were

observed. Admission laboratory values included a WBC count of 2.1x l09/liter, with 18% neutrophils, 76% small Iymphoctyes, 4%

monocytes, 1% blasts, and 1% metamyelocytes. The platelet count

was 5 x lO9/liter and Hct 18%. Electrolyte levels and other blood

chemistry tests at the time of admission were normal. Fibrinogen

was 0. 1 g/liter (normal, 0. 1-0.4 g/Iiter). The initial PT was I 8.5 sec

(control, 1 1 .9 see), and the PTT was 23.8 sec (control, 25. 1 see). An

admission cardiogram showed a sinus tachycardia with a rate of

120/mm and borderline left ventricular hypertrophy. Nonspecific

T-wave inversion was also seen. A chest x-ray showed no abnormali-

ty.

A BM aspirate obtained at the time of admission revealed a

hypercellular marrow, with numerous blasts replacing the normal

marrow elements. Many blasts had convoluted nuclei and very fine

cytoplasmic granules. A bone core biopsy done at the same time

showed an overall cellularity of 99%; no megakaryocytes and few

erythroid precursors were detected. The abnormal cells had folded,

Table 2. Light and El ectron M icroscopic Characte ristics (Bone Marrow)

Light MicroscopyCytochemistry

Ultrastructure

Average

GranulePercent

Hyper-

Percent

Faintly Percent Percent�‘anuIar Granulated Auer Px Positive ANAE Size Auer

Patient Promyeiocytes “Promyelocytes” FAB Bodies Nucleus Cells Cells RER (nm( Bodies

1 9 22 M2 Rare Irregular, folded,

bibbed

40 <5 Dilated 120 Rare

2 5 45 M2 Rare Irregular, folded,

bibbed

90 <5 Dilated 1 70 Rare

3 10 62 M� Rare Irregular, folded,

bibbed

99 40 Dilated 180 Rare

Px, peroxidase; ANAE. abpha-naptyl acetate esterase; RER, rough endoplasmic reticulum.

The presence of NaF-inhibited ANAE activity in 40% of the cells could indicate an M4 classification for this case if cytochemistry alone were

considered.

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MICROGRANULAR APL 255

irregular nuclei with large nucleoli. Approximately 60% of the cells

contained fine cytoplasmic granules; large, dark azurphilic granules

were seen in only 10% of the cells. One day after admission, FDP

were between I 280 and 2560 big/mI (normal, less than 20 jzg/ml).

Within 24 hr of admission and upon return of the FDP results, the

patient was begun on combination chemotherapy for her acute

leukemia. The treatment consisted of TAD, as for case 2. In

addition, continuous-infusion heparin was begun at 2000 U intrave-

nous push, to be followed by 600 U every hour continuously.

A repeat BM aspirate obtained I 3 days after the start of

treatment, when the hemtocrit was 35% (posttransfusion), WBC

count 0.4 x l09/liter, and the platelet count 69 x lOt/Iiter, showed

5% cellularity, with the majority ofcells consisting of promyelocytes

and blasts. At this time, the second course ofTAD was begun at the

same dosages and completed 5 days later. A BM specimen obtained

approximately 3 wk after the start of the second cycle of TAD

showed an overall cellularity of less than I %, with very few hemato-

poietic elements. No clusters of immature myeloid cells were noted.

A repeat BM aspirate 2 wk later, at a time when the WBC count

was 0.1 x 109/liter, showed little cellularity. Two weeks later, or

approximately 2 mo after the initial admission, the patient had a

WBC count of 2.4 x 109/liter with 52T neutrophils, 40 lympho-

cytes, 7% monocytes, and no blasts. The platelet count was 44 x

lOt/liter and the hematocrit 32%. Evaulation I I wk after initiation

ofTAD demonstrated normal blood counts, however, a BM aspirate

showed residual leukemia.

Clinical

RESULTS

The clinical characteristics of all patients are

summarized briefly in Table 1. All three patients

presented with bleeding complaints; the first two had

bleeding gums, the third had multiple ecchymoses as

well as a prolonged menstrual cycle. All three had

laboratory evidence of DIC with increased FDP.

Light and Electron Microscopy

Light-microscopic evaluation showed all three

patients to have less than 50% hypengranular promyel-

ocytes in their BM, but to have a significant percent-

age of promyelocytes with fine, dust-like granules,

often concentrated in one area of the cytoplasm (Table

2). In each case, more than 50% of the cells had

irregular, folded, and bibbed nuclei that resembled

monocytic nuclei (Fig. I ). Cytochemically, cells from

Fig. 1 . Representative cells from each of the three casesshow only faint cytoplasmic granulations by light microscopy.Similarities of nuclear irregularities are obvious (Wright Giemsa,*750).

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Fig. 2. (A) Low magnification transmission electron micro-graph of a bone marrow spicube from patient 3. Note the large

folded nuclei and the primary granules scattered throughout thecytoplasm (*4700). (B) Higher magnification of a cell from thesame patient. Many primary granules and dilated rough endoplas-

mic reticulum are visible (x18,200).

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256 GOLOMB ET AL.

patients 1 and 2 were positive for peroxidase and

naphthol AS-D-chloroacetate esterase, and fewer than

5% of the cells showed any positivity with the nonspe-

cific esterase reaction. For patient 3, more than 95% of

the abnormal cells had an intense peroxidase and

naphthol AS-D-chloroacetate esterase reaction. How-

ever, 40% of the cells showed a moderate reaction with

alpha-naphthyl acetate, and this esterase activity was

inhibited with sodium fluoride.

Ultrastructural examination demonstrated a dilated

endoplasmic reticulum in all three cases (Fig. 2). The

average granule sizes were I 20, 1 70, and I 80 nm for

patients I , 2, and 3 respectively. (The limit of resolu-

tion of light microscopy is approximately 250 nm.’3)

All granules were dense; those in case 3 were not

typical of monocytic differentiation despite the cyto-

chemical reactions observed. A histogram showing the

distribution of granules, according to size, of each of

the three patients is given in Fig. 3. Granules larger

than 250 nm comprised only 2%, 1 5� and 9� of the

total population of granules in patients I , 2, and 3

respectively. In addition to the data from these three

patients, the distribution of granule size is included for

two previously reported cases of classical hypengranu-

lan promyelocytic leukemia from our institution (Fig.

3, A and B). One of these patients3 had granules of an

average size of 640 nm, and all were larger than 250

nm; the second patient4 had granules of an average

size of 270 nm, approximately 50% being larger than

250 nm.

Cytogenetic

In each of the three patients, a I 5; 1 7 rearrangement

was present in a high percentage (799�-l00%) of the

metaphases from the initial sample (Table 3). The

structural rearrangement seemed to be identical in all

of the abnormal metaphases from patients I and 2 and

in one of the metaphases from patient 3 [t (15:17)

(q25?; q22?)]. All of the other abnormal metaphase

cells in patient 3, however, had another rearrange-

ment; whereas the translocation between nos. I 5 and

17 appeared to involve the breakpoints mentioned

above, the 17q- chromosome had additional uniden-

tified bands on the short arm (Fig. 4). The I7p+ q-

chromosome was submetacentnic with conventional

stain and did not appear to be an isochromosome of the

long arm of the deleted no. I 7 when it was examined

with quinarcrine fluorescence.

All three patients had one or more cytogenetic

analyses during the period of response, and each had a

normal karyotype during this time. Patient I showed

clonal evolution of the karyotype to further complexity

during relapse.7 Patients 2 and 3 continued to have

normal karyotypes as of May I 979.

Diameter of granules (nm)

Fig. 3. Histograms 1 . 2 and 3 illustrate the distribution ofprimary granules in the cells of three patients with microgranular

acute promyebocytic leukemia (API). The majority of granuleshave a diameter less than 250 nm. the limit of resolution of lightmicroscopy. Histograms A and B show the distribution of primarygranule size in the cells of two previously reported patients with

typical API, diagnosed by light microscopy. Although there is aheterogeneity of granule size, many granules with a diametergreater than 250 nm exist.

DISCUSSION

It seems clear that these three patients belong to a

subgroup of ANLL that has only recently been identi-

fled 7,8.14,15 There is disagreement as to the correct

classification of these patientst”5 It is our contention

that the clinical syndrome of DIC, the ultrastructural

determination of numerous primary granules, and the

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MICROGRANULAR APL 257

Table 3. Summary o f Cyto genetic Findings

Patient

Sample

Date

Sample

Source’

No. of Metaphases

PercentWith

t) 1 5; 1 �)t Karyotype

No. of Chromosomes

Totalt<44 44 45 46 >46

1 12-01-76 BM, PB 5 0 4 22 0 31(14) 79 46,XY/46,XY,t)15;17)(q25?;q22?(�1

2 6-12-78 BC 3 2 7 10 0 22(14) 93 46,XX�/46.XX,t(15;17)(q25?;q22?)

3 2-6-79 BM 1 6 10 18 0 35(21) 100 46,XX,t)15;17)(q25?;q22?)�

‘BC. bone core biopsy; BM, bone marrow aspirate; PB, peripheral blood (without PHA).

tNumber in parentheses indicates number of informative metaphases examined in detail with fluorescence.

�Ca(culated as percent informative metaphases examined with fluorescence.

§Only one metaphase seen in this sample showed a normal karyotype.

#{182}Subsequent samples at the time of relapse showed clonal evolution to a more complex karyotype.

�ln 20 of 2 1 banded metaphases, the 1 7q - had additional unidentified bands on the short arm.

cytogenetic findings of the t(15:17) combine to iden-

tify this subgroup as a variant of acute promyclocytic

leukemia, which we have chosen to call the “micro-

granular” type.

All 3 patients had DIC, which is consistent with the

observation of Sultan et al.16 that, of 140 consecutive

patients who had ANLL, 17 of 18 patients with

abnormal coagulation tests had APL.

Although our three patients had less than 10%

hypergranular cells, with a larger percentage of cells

containing only dust-like granules by light micro-

scopy, TEM showed that the majority of cells in these

patients contained many granules that were less than

250 nm in size and thus smaller than the limit of

resolution of light microscopy. By light microscopy,

however, similarities were observed in the nuclear

configuration in the cells of these three patients and in

four of our patients with the more classic variety of

Fig. 4. Karyotype of a Q-banded metaphase cell obtained from a BM sample from patient 3. The metaphase has a transbocationbetween the long arms of one no. 15 and one no. 17 [t(15;17)(q25?;q22?)]. The abnormal 17 also has additional unidentified bands on theshort arm. Inset: partial karyotype of pairs 15 and 17 from another metaphase from the same BM sample; there is a t(15;17)(q25?;q22?).but without any alteration of the short arm of the abnormal 17.

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I1��50 00 50 200250 300 350400430 500

D,omeie� oi g�o,,iiies nm)

Fig. 5. Histogram represents the distribution of primarygranule size in the cells of a patient with acute myelogenousleukemia with maturation (M2). The distribution is similar to thatseen in the cases of microgranular acute promyebocytic leukemia.

258 GOLOMB ET AL.

APL; reniform, folded, and bibbed monocyte-like

nuclei were numerous in each. Cells from all three

patients contained extremely dilated rough endoplas-

mic reticulum (RER), although one patient also had

cells with nondilated RER. Dilated RER in the

promyelocytes of APL patients was recently reported

by Parkin and Brunning.’7

The specificity of the 15;17 translocation for APL

has been suggested by our group in a study of 90

ANLL patients, 4 of whom (including one from the

present study) had the t(l5;17); all 4 had APL.’8

Recently Van Den Berghe et al.5 reported a t(l5;l7)

(q26;q22) in 1 1 of 16 APL patients. A l5;17 translo-

cation has also been reported for APL patients seen by

several other investigators.92’ This rearrangement

was observed in 9 of I 7 APL patients reviewed at the

First International Workshop on Chromosomes in

Leukemia;6 in contrast, it was not seen in any of the

224 patients who had other forms of AN LL.

The 15;17 structural rearrangement in patients I

and 2 was identical to that seen in four of our

previously reported patients with classic hypergranu-

lan promyelocytic leukemia.8 The breakpoints in the

long arm of nos. I 5 and 1 7 in patient 3 also appeared

to be identical to those in these other patients; howev-

er, in patient 3 the 17q- chromosome had additional

unidentified material on the short arm in all but one of

the abnormal cells. The metaphase with the usual

t(15;l7) in patient 3 probably represents the original

abnormal clone, whereas the metaphases with the

I 7p + q - represent a subsequent structural rearrange-

ment in this clone.

Although the diagnosis of “microgranular” APL

seems warranted from the data presented, the positive

ANAE reaction in case 3 remains to be explained.

Analysis of case 3 by TEM showed only primary

granules; there was no evidence of monocytic granules.

Although the positive ANAE reaction is more in

keeping with a monocytic origin of some of the cells, a

similar pattern has been described previously for the

cytochemistry of APL22’23 Thus, the positive ANAE

reaction in case 3 would suggest a FAB classification

of M4 yet TEM evaluation would demand an M3

designation. Cases I and 2 would have been classified

as an M2 by light microscopy and cytochemistry, but

TEM analysis would require an M3 designation.

Recently, Bergen et al.14iS reported on three pa-

tients with a t(15;I7) who showed a type of ANLL

similar to that of the patients in this report. They

classified their patients as AML, although they

acknowledged that they were atypical. Their cases

were characterized by a high WBC count, monocyte-

like myeloblasts, DIC, and a t(I5;17) in the majority

of leukemic cell mitoses. Light microscopy showed

reniform folded nuclei, as described in our three cases;

cytochemistry yielded positive peroxidase, but essen-

tially negative napthal AS-D-chloracetate esterase and

ANAE. Transmission electron micrographs were not

labeled by cases; most cells had reniform nuclei and

sparse primary granules; there was one example of a

cell with multiple Auer rods.

We recently used TEM to analyze the cell ultra-

structure of 25 patients with ANLL (Butler A, et al.,

unpublished observations). One patient, a 37-year-old

white woman, had no DIC, had a normal karyotype,

and was classified by the FAB system as M2 (i.e.,

acute myelogenous leukemia with some maturation).

By TEM analysis, the majority of cells were found to

contain numerous granules that averaged 190 nm in

size and were similar in distribution to those in our 3

patients with microgranular APL (Fig. 5).

It seems to us, therefore, that there are patients with

ANLL that form a distinct subgroup, although there

is some variability in the morphology and cytochemis-

try of the leukemic cells. This group is characterized

by a hematologic history and laboratory evidence of

DIC; by cytochemical findings that are predominantly

myelocytic, but with an occasional case with mono-cytic staining characteristics; by ultrastructural find-

ings of few to many cytoplasmic primary granules that

are usually smaller than the resolution of light micro-

scopy; and by the presence of the t(15;17). In view of

the number of features that are typical of classical

APL, we prefer to classify these patients as APL,

“microgranular” variant. It is apparent, however, that

there is a spectrum of morphological forms from

myeloblastic through promyelocytic to monocytic; the

precise position within this continuum of the patients

presented in this report must await the careful cyto-

genetic, cytochemical, and TEM analysis of additional

patients.

It is important clinically to make the correct diagno-

sis of APL as early as possible in order to initiate

appropriate therapy. Bernard et al.24 showed that

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MICROGRANULAR APL 259

15. Berger R, Bernheim A, Daniel, M-T, Valensi R, Flandrin G,

daunorubicin can induce remission in about 50% of

APL patients with a median survival of 26 mo.

Drapkin et al.25 suggested that prophylactic hepanin

along with chemotherapy may allow a better chance of

induction remission. Thus, it is important that possible

cases of APL be studied cytochemically, ultrastructu-

rally, and cytogenetically; the determination of the

diagnosis of APL has therapeutic importance.

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Br J Haematol 33:451-458, 1976

2. Jones ME, Suleem A: Acute promyelocytic leukemia. Am J

Med 65:673-677, 1978

3. Golomb HM, Rowley JD, Vardiman JW, Baron JM, Locker

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ADDENDUM

Since acceptance of this manuscript, the French-

American-British (FAB) Group have suggested recog-

nition of a variant form of hypergranular promyelo-

cytic leukemia (M3) in which the cells are character-

ized by bibbed, multilobed, or reniform nuclei, and

cytoplasm with minimal or no granulation. A few cells

with the features of typical M3 will be present in such

instances. The cases in this report correspond to this

variant group. [Bennet JM, Catovsky D, Daniel MT.

Flandrin G, Galton DAG, Gralnick HR, Sultan C: A

variant form of hypergranular promyelocytic leukemia

(M3). Br J Haem (in press)].

For personal use only.on April 3, 2019. by guest www.bloodjournal.orgFrom

1980 55: 253-259  

HM Golomb, JD Rowley, JW Vardiman, JR Testa and A Butler ultrastructural, and cytogenetic entity"Microgranular" acute promyelocytic leukemia: a distinct clinical, 

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