Acute promyelocytic leukemia

Abstract

We conducted a retrospective review of pathology files and hospital records and identified three unusual presentations of granulocytic sarcoma associated with acute myeloid leukemia (AML) of the head and neck. At least one mass was observed on the skin of all three patients. A 17-year-old boy had masses in each temporal region that were accompanied by bilateral facial paralysis. He was administered chemotherapy and radiotherapy, but he died of infection secondary to a second relapse 29 months after the initial diagnosis. A 17-year-old girl had a tumor in the right parotid area. She received chemotherapy, but she died of infection and bleeding 2 months after the initial diagnosis. A 33-year-old man had numerous tumors widely disseminated over his skin. He received chemotherapy and was in remission 12 months after the initial diagnosis, but he eventually relapsed and died. Granulocytic sarcoma can be localized in unexpected regions, including the head and neck. This tumor is very often misdiagnosed as a maligna nt lymphoma, which leads to delayed treatment and a poor outcome. Therefore, clinical and histopathologic findings should be evaluated before any diagnosis of malignant lymphoma is pronounced. Immunohistochemical stains should also be performed on patients with suspected granulocytic sarcoma, and aggressive chemotherapy or immunotherapy should be administered. We believe that high-dose chemotherapy can improve survival rates in granulocytic sarcoma associated with AML.

Introduction

A granulocytic sarcoma is a rare, extramedullary, solid aggregate of malignant myeloid precursor cells. The term granulocytic sarcoma was first used by Rappaport in 1966. [1] This malignancy is also known as a chloroma.

In this article, we describe three unusual presentations of granulocytic sarcoma that were associated with acute myeloid leukemia (AML). One patient had bilateral facial paralysis caused by temporal bone involvement of bilateral granulocytic sarcoma; we believe that this is the first such reported case in the literature. Another patient exhibited parotid gland involvement; we determined that this is only the second such reported case. The third patient had 12 tumors widely disseminated over his skin; to our knowledge this is the first reported case in the literature. In addition to these case reports, we also discuss the clinical behavior, histopathology, treatment, and prognosis of granulocytic sarcoma associated with AML of the head and neck region.

Case reports

Patient 1. In January 1996, a white 17-year-old boy was admitted to our hospital with a 2-week history of weakness and fever. On admission, the patient's general condition was poor. Physical examination revealed pallor, diffuse petechia and purpura, and hepatosplenomegaly. Morphologic, cytochemical, and immunocytochemical studies confirmed the diagnosis of AML (M4-FAB). He was administered the standard chemotherapeutic regimen for remission induction of AML.

After 21 months of therapy, the patient was readmitted because of a sudden onset of bilateral facial paralysis, a sudden hearing loss, vision disturbance, and the appearance of a firm, painful, rapidly growing mass in each of his postauricular areas. The masses were 7 and 5 cm in diameter on the right and left, respectively; the skin covering the two masses was normal. On computed tomography (CT), the masses could be seen in both temporal regions (figure 1).

The patient's white blood cell count (WBC) was 150 x [10.sup.9]/L. An incisional biopsy of the mass in the right postauricular area was obtained, and the histopathologic examination revealed a highly cellular tumor. The patient was given a histopathologic diagnosis of granulocytic sarcoma (his first relapse). At this time, leukemic cells were observed in bone marrow. He was placed on a chemotherapeutic regimen of daunorubicin and cytosine arabinoside (ARA-C) for remission induction of AML.

Following chemotherapy, a CT examination found no evidence of tumor in either postauricular area, and the patient's facial paralysis had subsided. The patient was then administered a 10-day regimen of radiotherapy (240 cGy/day) delivered to both temporal regions.

Two months later, the patient experienced a second relapse and his condition deteriorated. Leukemic cells were observed in the peripheral smear and in bone marrow. Further induction chemotherapy was planned, but the patient died of infection before it could be initiated. His death came 2 years and 5 months after the initial diagnosis. An autopsy was not performed.

Patient 2. In June 1998, a white 17-year-old girl was admitted to our hospital with a 3-month history of abdominal pain, right preauricular swelling, weight loss, and weakness. On admission, her general condition was poor, and her physical examination showed pallor and an ill-defined soft mass measuring 5 cm in diameter in the right preauricular area; the skin covering the mass was erythematous. In addition, bilateral cervical and submandibular lymphadenopathy and hepatosplenomegaly were observed.

The patient's WBC, platelet, and hemoglobin levels were 3.5 x [10.sup.9]/L, 17 x [10.sup.9]/L, and 8 g/dl, respectively. Morphologic, cytochemical, and immunocytochemical studies, including peripheral smear and bone marrow aspiration analyses, confirmed the diagnosis of AML (M4-FAB). Ultrasonographic examination showed that the right parotid gland and its covering skin had been infiltrated by tumor (figure 2). Fine-needle aspiration biopsy of the mass revealed that the tumor cells were immature blast forms. The cytopathologic diagnosis was granulocytic sarcoma. The patient was administered the standard chemotherapeutic regimen for remission induction of AML.

Evaluation on day 28 following the cessation of chemotherapy showed no remission, and the marrow aspiration and biopsy showed more than 5% blasts. However, no evidence of tumor was noted in the right preauricular area on ultrasonographic examination, and no blast was detected in the peripheral smear. Taken together these findings were considered to represent a partial remission. and a course of reinduction chemotherapy was planned. However, the patient refused a second round of therapy.

One month later, she was readmitted to the hospital in poor condition. Her peripheral smear showed 80% blasts. Ten days later, she died of infection and bleeding. An autopsy was not performed.

Patient 3. In December 1997, a white 33-year-old man was admitted to the hospital with a 4-month history of multiple masses on his skin. A previous skin biopsy had been misdiagnosed by the pathologist as a malignant lymphoma, and the patient had undergone three courses of chemotherapy. When his general condition had not improved and his masses had not disappeared, he returned to seek further treatment. On admission, the patient's general condition was poor. Physical examination showed fever, bilateral cervical and axillary lymphadenopathy, and splenomegaly. The skin was marked by 12 soft, tender, nonulcerated, and violaceous nodules, which varied in diameter from 4 to 12 cm (figure 3).

The patient's WBC, platelet, and hemoglobin levels were 150 x [10.sup.9]/L, 60 x [10.sup.9]/L, and 6 g/dl, respectively. Bone marrow aspiration detected 85% monoblasts. Morphologic, cytochemical, and immunocytochemical studies confirmed the diagnosis of AML (M5A-FAB). An incisional biopsy of the tumor showed that the tissue was made up of large immature mononuclear cells, which featured high nuclear-cytoplasmic ratios and immature nuclear chromatine patterns (figure 3). The nuclei were round to oval and had one or two prominent nucleoli. The histopathologic diagnosis was granulocytic sarcoma. The patient was placed on the standard chemotherapeutic regimen for remission induction of AML.

Evaluation on day 26 following the cessation of remission-induction therapy showed no remission. The patient's lesions were smaller, but they had not disappeared. He was therefore administered reinduction chemotherapy, which consisted of daunorubicin, etoposide, and ARA-C.

Evaluation on day 28 following reinduction therapy showed that the patient's masses had disappeared and that he was in remission. Two identical courses of reinduction chemotherapy were then given for consolidation.

By August 1998, the patient was still in remission and an allogenic peripheral stem cell transplant was suggested. However, the patient could not afford this treatment, so postconsolidation immunotherapy with interleukin-2 was initiated instead. However, 3 months later he relapsed and died.

Discussion

Granulocytic sarcoma usually involves the bone, soft tissue, lymph nodes, and skin. [2] It rarely involves the parotid area. [3] Although leukemic infiltration of the temporal bone is seen occasionally, symptomatic facial nerve involvement is extremely rare, even in patients with granulocytic sarcoma. [4] Through January 2001, only three cases of unilateral facial paralysis secondary to temporal bone involvement of unilateral granulocytic sarcoma associated with AML have been reported in the English-language literature. [5-7] To our knowledge, our case represents the first report of bilateral paralysis. Involvement of the parotid gland is extremely rare in granulocytic sarcoma associated with AML; as far as we know, only one other case has been reported in the English-language literature. [3]

Granulocytic sarcoma usually develops before or during the course of myeloid leukemia. [2] One of our cases (patient 1) was diagnosed as granulocytic sarcoma 2 years after the AML diagnosis. The other two patients were diagnosed with granulocytic sarcoma after they had been admitted to the hospital.

There are three types of skin involvement in AML: nonspecific lesions, [8] leukemia cutis, [9] and granulocytic sarcoma. [10] The most common initial symptoms in patients with temporal bone involvement are postauricular aching and swelling, hearing loss, otalgia, and tinnitus. [6,11] Facial and acoustic nerve paralysis can subsequently develop as a result of a perineural and/or meningeal leukemic infiltration associated with hemorrhage, edema, or an adverse reaction to drug therapy. [12] One of our patients (patient 1) had bilateral temporal bone involvement, bilateral facial paralysis, hearing loss, and vision disturbance.

Histochemical and immunohistochemical techniques allow for a conclusive diagnosis of granulocytic sarcoma, even with routinely processed paraffin-embedded material. [13] Histopathologically, this diagnosis is often difficult to make in patients who do not have acute leukemia. As many as 75% of these tumors are initially misdiagnosed, most as malignant lymphoma. [14,15] This is precisely what had happened in one of our three cases (patient 3).

Patients with granulocytic sarcoma associated with AML have a poor prognosis. [16] Patients are routinely treated with chemotherapy, with or without radiotherapy, but as many as 85% relapse within 1 year. 17] Therefore, the definitive treatment should be chemotherapy followed by hematopoietic stem cell transplantation. When transplantation is not possible, we believe that chemotherapy might still improve survival rates if it is administered in higher doses than usual.

References

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