Head and neck granulocytic sarcoma with acute myeloid leukemia: Three rare cases.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 AML - A Manufacturing Language ) 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 parotid /pa·rot·id/ (pah-rot´id) near the ear.
1. Situated near the ear.
2. Of or relating to a parotid gland.
A parotid gland. 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.
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.  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 his·to·pa·thol·o·gy
The science concerned with the cytologic and histologic structure of abnormal or diseased tissue.
The study of diseased tissues at a minute (microscopic) level. , treatment, and prognosis of granulocytic sarcoma associated with AML of the head and neck region.
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 petechia /pe·te·chia/ (pe-te´ke-ah) pl. pete´chiae [L.] a minute red spot due to escape of a small amount of blood.pete´chial
n. pl. and purpura purpura
Presence of hemorrhages in the skin, often associated with bleeding from natural cavities and in tissues. Major causes include damage to small artery walls (as in vitamin deficiency or allergic reaction) and platelet deficiency (in association with such disorders as , 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 white blood cell count,
n a diagnostic clinical laboratory test to determine the number and types of leukocytes present in a measured sample of blood. Overall the normal number of leukocytes ranges from 5000 to 10,000/mm3. (WBC WBC white blood cell; see leukocyte.
white blood cell
n stands for white
cell. ) 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 daunorubicin /dau·no·ru·bi·cin/ (daw?no-roo´bi-sin) an anthracycline (q.v.) antibiotic used as an antineoplastic; administered as the hydrochloride salt or as a liposome-encapsulated preparation of the citrate salt. and cytosine arabinoside (ARA-C ara-C cytarabine.
cytosine arabinoside; see cytarabine.
ara-C Cytarabine, see there ) 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 erythematous
characterized by erythema. . In addition, bilateral cervical and submandibular submandibular /sub·man·dib·u·lar/ (sub?man-dib´u-ler) below the mandible.
submandibular (sub´mandib´y lymphadenopathy lymphadenopathy /lym·phad·e·nop·a·thy/ (-op´ah-the) disease of the lymph nodes.
angioimmunoblastic lymphadenopathy , angioimmunoblastic lymphadenopathy with dysproteinemia 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 splenomegaly /sple·no·meg·a·ly/ (-meg´ah-le) enlargement of the spleen.
congestive splenomegaly Banti's disease; splenomegaly secondary to portal hypertension. . The skin was marked by 12 soft, tender, nonulcerated, and violaceous violaceous /vi·o·la·ceous/ (vi?o-la´shus) having a violet color, usually describing a discoloration of the skin. nodules Nodules
A small mass of tissue in the form of a protuberance or a knot that is solid and can be detected by touch.
Mentioned in: Leprosy , 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 nucleoli
plural form of nucleolus. . 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.
Granulocytic sarcoma usually involves the bone, soft tissue, lymph nodes, and skin.  It rarely involves the parotid area.  Although leukemic infiltration of the temporal bone is seen occasionally, symptomatic facial nerve involvement is extremely rare, even in patients with granulocytic sarcoma.  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. 
Granulocytic sarcoma usually develops before or during the course of myeloid leukemia.  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,  leukemia cutis,  and granulocytic sarcoma.  The most common initial symptoms in patients with temporal bone involvement are postauricular aching and swelling, hearing loss, otalgia otalgia /otal·gia/ (o-tal´jah) pain in the ear; earache.
Pain in the ear; earache.
o·tal , and tinnitus. [6,11] Facial and acoustic nerve paralysis can subsequently develop as a result of a perineural and/or meningeal me·nin·ge·al
Of, relating to, or affecting the meninges.
pertaining to the meninges.
meningeal hemorrhage leukemic infiltration associated with hemorrhage, edema, or an adverse reaction to drug therapy.  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.  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.  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 hematopoietic stem cell transplantation Hematology A therapy in which defective hematopoietic cells are replaced with normal BM cells after chemotherapy and/or RT Indications AML, breast CA, CML, germ cell tumors, lymphoma, myelodysplastic syndrome, myeloma, . When transplantation is not possible, we believe that chemotherapy might still improve survival rates if it is administered in higher doses than usual.
(1.) Rappaport H. Tumors of the Hematopoictic System. Washington. D.C.: Armed Forces Institute of Pathology Armed Forces Institute of Pathology A section of the US military which provides consultations, reference atlases and educational programs for pathologists , 1966:241-3.
(2.) Saleh HA, Khatib G. Fatal gastrointestinal bleeding as the primary manifestation of granulocytic sarcoma in a patient with myclodysblastic syndrome. J Fla Mcd Assoc 1997;84: 11-4.
(3.) Dufour C, Garaventa A, Brisigotti M, et al. Massively diffuse multifocal multifocal /mul·ti·fo·cal/ (mul?te-fo´k'l) arising from or pertaining to many foci.
Relating to or arising from many foci. granulocytic sarcoma in a child with acute myeloid leukemia. Tumori 1995;81:222-4.
(4.) Zappia JJ, Bunge FA, Koopmnann CF, McClatchcy KD. Facial nerve paresis paresis /pa·re·sis/ (pah-re´sis) slight or incomplete paralysis.
general paresis paralytic dementia; a form of neurosyphilis in which chronic meningoencephalitis causes gradual loss of cortical as the presenting symptom of leukemia. Int J Pediatr Otorhinolaryngol 1990; 19:259-64.
(5.) Almadori G, Del Ninno M, Cadoni G, et al. Facial nerve paralysis Facial nerve paralysis is a common problem that involves the paralysis of any structures innervated by the facial nerve. The pathway of the facial nerve is long and relatively convoluted, and so there are a number of causes that may result in facial nerve paralysis. in acute otomastoiditis as presenting symptom of FAB M2, T8;2 I leukemnic relapse. Case report and review of the literature. Int J Pediatr Otorhinolaryngol 1996:36:45-2.
(6.) Todd NW, Bowman CA. Acute myclogenous leukemia presenting as atypical mastoiditis mastoiditis
Inflammation of the mastoid process, a bony projection just behind the ear, almost always due to otitis media. It may spread into small cavities in the bone, blocking their drainage. Very severe cases infect the whole middle ear cleft. with facial paralysis. Int J Pediatr Otorhinolaryngol l984;7: 173-7.
(7.) Wuillemin WA, Vischer MW, Tobler A, Fey MF. Relapse of acute myeloblastic leukaemia presenting as temporal bone chloroma with facial nerve paralysis. Ann Oncol l993:4:339-40.
(8.) Braverman IM. Leukemia and allied disorders. In: Braverman IM, ed. Skin Signs of Systemic Disease. Philadelphia: W.B. Saunders, 1981:179.
(9.) Shaikh BS. Frantz E, Lookingbill DP. Histologically proven leukemia cutis carries a poor prognosis in acute nonlymphocytic leukemia acute non·lym·pho·cyt·ic leukemia
See acute myelogenous leukemia. . Cutis cutis /cu·tis/ (ku´tis) the skin.
cutis anseri´na transitory elevation of the hair follicles due to contraction of the arrectores pilorum muscles; a reflection of sympathetic nerve discharge. 1987;39:57-60.
(10.) Sun NC, Ellis R. Granulocytic sarcoma of the skin. Arch Dermatol 1980:116:800-2,
(11.) Chapman P. Johnson SA. Mastoid mastoid /mas·toid/ (mas´toid)
2. mastoid process.
3. pertaining to the mastoid process.
The mastoid process. chloroma as relapse in acute myeloid leukaetnia. J Laryngol Otol 1980:94:1423-7.
(12.) Rontal E, Sigel ME. Bilateral facial paralysis. Laryngoscope 1972;82:607-16.
(13.) Roth MJ, Medeiros U, Elenitoba-Johnson K, et al. Extramedullary mycloid cell tumors. An immunohistochemical study of 29 cases using routinely fixed and processed paraffin-embedded tissue sections. Arch Pathol Lab Med 1995;l 19:790-8.
(14.) Frohna BJ. Quint DJ. Granulocytic sarcoma (chloroma) causing spinal cord compression Spinal cord compression develops when the spinal cord is compressed by bone fragments from a vertebral fracture, a tumor, abscess, ruptured intervertebral disc or other lesion. . Neuroradiology neuroradiology /neu·ro·ra·di·ol·o·gy/ (-ra?de-ol´ah-je) radiology of the nervous system.
1. The branch of radiology that deals with the nervous system. l993;35:509-11.
(15.) Colle I, Lacor P. Peeters P, et al. Granulocytic sarcoma (chloroma): A report of two cases. Acta Clin Belg 1996:51:106-10.
(16.) Neiman RS, Barcos M, Berard C, et al. Granulocytic granulocytic
pertaining to granulocytes.
see myelocytic leukemia.
extramedullary growth of multiple, focal granulocytic neoplasm. They may be neutrophilic or eosinophilic. sarcorna: A clinicopathologic study of 61 biopsied cases. Cancer 1981; 48:1426-37.
(17.) Lichtman MA. Acute myelogenous leukemia acute myelogenous leukemia
n. Abbr. AML
Myelogenous leukemia characterized by rapid abnormal increase in the number of myeloblasts and progression of symptoms. . In: Beutler E, Lichtman MA, Coller BS, Kipps TJ, eds. Williams Hematology. New York: McGraw-Hill, 1995:272-88.