Chloroma of perianal region masquerading as perianal abscess.

Chloroma, also called granulocytic sarcoma (GS) or Myeloid Sarcoma, is a rare malignant extra-medullary neoplasm of myeloid precursor cells. It is usually associated with myeloproliferative disorders but its appearance may precede the onset of leukaemia. The presence of a chloroma is certainly a sign of poor prognosis. We report a case of chloroma in a middle aged female without a prior history of leukemia in the perianal skin region with clinical diagnosis of perianal abscess. When there is no concomitant leukaemia, diagnosis of chloroma may be difficult. Differential diagnoses include acute lymphoblastic leukemia, large cell NHL, lymphoblastic lymphoma, Ewing's sarcoma and cutaneous T cell lymphoma.

What was known?

It was first described by the British physician A. Burns in 1811.This name is derived from the Greek word chloros (green), as these tumors often have a green tint due to the presence of myeloperoxidase. It is commonly described with acute myeloid leukemia but can precede the leukemia

Introduction

Chloroma is a rare malignant extra-medullary neoplasm of myeloid precursor cells. It was first described by the British physician A. Burns in 1811.This name is derived from the Greek word chloros (green), as these tumors often have a green tint due to the presence of myeloperoxidase. It is commonly described with acute myeloid leukemia but can precede the leukemia.[12] It rarely develops in patients without symptoms of leukemia, either in the peripheral blood or in bone marrow. In most of these patients, following the occurrence of chloroma, an overt acute myeloid leukaemia develops within 1 to 49 months. The most common areas of involvement are the skin (also known as leukemia cutis) and the gums. Other tissues include lymph nodes, small intestine, mediastinum, epidural sites, uterus, and the ovaries. Symptoms of chloroma at these sites are related to their anatomic location; chloromas may also be asymptomatic and be discovered incidentally in the course of evaluation of a person with acute myeloid leukemia. In our case, initial presentation was abscess in perianal region which was diagnosed as chloroma and the patient subsequently found to have sub leukemic leukemia.

Case Report

A 50-year-old female complained of a swelling in her perianal region for the last two months and all the relevant biochemical and hematological investigation were found to be normal. On peripheral blood film examination patient was mildly anemic with a total leukocyte count of 4000/cmm and differential leucocyte count of P 50 L48 M1 E1 B0 with normal platelet count. Clinical diagnosis of perianal abscess [Figure 1] was made. The abscess was drained, but it didn’t heal and persisted in the perianal region. After two months, wedge biopsy was taken and submitted for histopathological examination. Macroscopically, a partially skin covered soft tissue piece measuring 1.0 × 0.8 × 0.3 cm was received. The biopsy revealed skin and subcutaneous tissue with dense infiltration by small round cells in sheets and trabeculae, enveloping the adnexal structures and infiltrating the subcutaneous fat [Figure 2]. A provisional diagnosis of malignant small round cell tumor was given and the biopsy was subjected to panel of immunohistochemical markers. The initial panel of cytokeratin, neuron specific enolase synaptophysin, chromogranin was negative and LCA was positive [Figure 3]. Subsequent IHC showed that cells were negative for CD 20 and tdt; (Terminal deoxynucleotidyl transferase) positive for myeloperoxidase [Figure 4] and focal positive for CD3. The peripheral blood film examined showed pancytopenia. Bone marrow showed a cellular marrow with a blast count of approximately 50%. Finally, the diagnosis of Acute Myeloid Leukemia with granulocytic sarcoma (GS)/chloroma of the perianal region were given. To our knowledge, there has not been a previous report of acute leukemia presenting as granulocytic sarcoma masquerading as perianal abscess.

Figure 1

Perianal abscess

Figure 2

Biopsy revealing infiltration by small round cells in dermis (H and E, ×100)

Figure 3

LCA positive (×100)

Figure 4

MPO positive (×100)

Discussion

Chloromas are rare extra-medullary neoplasms. Recently, it has been described as Myeloid Sarcoma, a distinct entity in 2008 WHO Classification. It is defined as myeloid blasts with or without maturation that grow to form “a tumor mass with effacement of tissue architecture. In about 70% of cases, they occur during the course of AML, or chronic myelo-proliferative disorders. It develops mostly concomitantly with the FAB subtype M5a, M5b M4 and M2 of the AML.[3]

Macroscopic examination of a chloroma is characterized by a greenish mass due to the presence of the myeloperoxidase enzyme in the immature granulocytic cells. Very rarely, myeloperoxidase is absent and the mass is not characterized by the classic green color up to 30% of these tumors can be white, gray, or brown.[4] Routine histological examination of these tumors shows a pleomorphic infiltrate of primitive cells of varying size and nuclear configuration.[5] Haematoxylin-eosin (H and E) staining does not identify granulocytic cells and the neoplasm may appear histologically as a sheet of round cells with no recognizable pattern, as seen in the present case. The histological diagnosis may be difficult due to the poorly differentiated myeloblasts in the absence of characteristic peripheral blood film findings. The tumours that can be confused with chloroma are poorly differentiated lymphoblastic lymphoma, large cell lymphoma, Ewing sarcoma, cutaneous T cell lymphoma as well as primitive neuroepithelial tumors. Immunohistochemistry is the mainstay in the diagnosis of such cases.

Tumor cells in large cell lymphoma have large, vesicular, irregularly shaped nuclei (indented, kidney-shaped, poly lobated) and give positive staining for CD45, CD20, and CD 30 in about 70% cases. In our case the cells did not have indented nuclei and cells were negative for CD20. Ewing's sarcoma and other primitive neuroectodermal tumors are common between 10 and 30 years of age. They usually occur in deep soft tissue and rarely involve dermis and subcutis. PAS positivity is present in about 40% of cases. A peripheral neuroepithelioma must demonstrate positivity with at least two neural markers. In our case the neural markers, neuron-specific enolase and synaptophysin were negative.

Lymphoblastic Lymphoma is a clinically aggressive lymphoma (high grade) composed of monomorphic lymphoid infiltrate with high proliferative activity and apoptosis. T-cell markers are positive in 80-85% cases and 15-20% of cases express B-cell rather than T-cell markers such as tdt, CD19, CD20, CD21 and CD24. In our case B-cell marker were negative and T–cell markers were focally positive. Another differential diagnosis is cutaneous T cell lymphoma; it represent a spectrum of lymphoproliferative disorders affecting the skin. There are three classical cutaneous phases of CTCL – patches, infiltrated plaques, and tumors – which were described by Bazin.[6] The disease may progress through each of these phases, which frequently overlap or occur simultaneously. In our case, there were small round cells in the dermis but characteristic features like epidermotropism, Pautrier microabscess and Sezary cells in blood, were absent. Thus, cutaneous T cell lymphoma was ruled out.

Historically, even with a tissue biopsy, pathologic misdiagnosis was an important problem, particularly in patients without a clear pre-existing diagnosis of acute myeloid leukemia to guide the pathologist. In one published series on chloroma, the authors stated that 47% patients were initially misdiagnosed, most often as having a malignant lymphoma. The increasingly refined use of immunohistochemistry and flow cytometry has facilitated more accurate diagnosis of these lesions.

The prognosis of acute, non-lymphocytic leukaemia that is associated with chloroma, even if poor, has decisively improved due to the development of more adequate and effective associations of chemotherapeutic drugs.[7] Chloromas are radiosensitive and local radiotherapy can be associated with chemotherapy. The earlier detection of extra-medullary granulocytic sarcomas could better define the real prognosis.

What is new?

Recently, it has been described as Myeloid Sarcoma, a distinct entity in 2008 WHO Classification. It is defined as myeloid blasts with or without maturation that grow to form “a tumor mass with effacement of tissue architecture. Up to 30% of these tumors can be white, gray, or brown