This patient was a rare case of AUL accompanied by lymph node masses. Lymph node flow cytometric analysis showed that the immunophenotype of lymph node tumour cells was consistent with the immunophenotype of leukaemia cells from his bone marrow, which was consistent with AUL. According to biopsy, the lymph node structure was destroyed, and immunohistochemistry showed that the tumour cells of the lymph nodes and bone marrow were identical and consistent with AUL. Therefore, this case was in line with a diagnosis of AUL with extramedullary sarcoma. We conducted a literature search, and to the best of our knowledge, this is the first report of AUL with extramedullary sarcoma.
AUL belongs to acute leukaemias of ambiguous lineage (ALAL) and is characterized by lack of lineage-specific antigens in leukaemia cells and expression of no or only one myeloid leukaemia-related immune marker(2). This type of leukaemia is extremely rare. A total of 1888 AUL cases diagnosed from 2000 to 2016 are found in the US SEER database, with an incidence rate of approximately 1.34 persons/million(2). With the advancement of diagnostic technology, the number of true AUL cases has been decreasing yearly(2). Patients with AUL are often older, with a median age of 75 years, and 70% of patients are over 60 years old. Compared with other AMLs, AUL has a worse prognosis, and the median survival time is significantly shorter than that of AML(3). The diagnosis of AUL mainly relies on bone marrow flow cytometry to analyse immune markers of leukaemia cells(3). The WHO defines AUL as a leukaemia that expresses neither lymphoid markers nor myeloid markers and for which NK-cell precursors, basophils, and even nonhaematopoietic tumours need to be excluded. Weinberg et al. reported 24 cases of AUL, with no significant difference from AML-M0 in terms of age of onset, blood cell count, degree of bone marrow hyperplasia, and ratio of bone marrow blasts(3). In terms of immunophenotype, myeloid markers, including CD13, CD33, and CD117, were not expressed in 6 cases; in 15 cases, 1 myeloid marker was partially or completely expressed, and 1 myeloid marker plus another myeloid marker were partially or weakly expressed in 3 cases. In our case, blasts from both the bone marrow and lymph nodes expressed only one myeloid marker, CD33. In Weinberg's study, B cell markers such as CD19, CD20, and CD10 were not expressed in 24 cases of AUL, but in 5 cases, cytosolic CD22 or cytosolic CD79a was partially expressed(3). No case expressed cCD3 or sCD3, but expression of other T cell-related antigens was common, with CD7 being the most common. In AUL, blasts rarely express more than one monocyte marker; two cases expressed CD11b, and only one case was partially positive for nonspecific esterase. The blasts in our patient expressed CD7 but were negative for sCD3 and cCD3, and no monocyte marker was positive.
AML with minimal differentiation, also known as AML-M0, is a more common AML subtype with no morphological or cytochemical evidence of myeloid differentiation and can easily be confused with AUL. Myeloid maturation of blasts in AML-M0 is demonstrated by immunological markers. The most vital myeloid marker, MPO, is often negative by cytochemistry but may be positive in some blasts by flow cytometry or immunohistochemistry. Blasts of AML-M0 express at least two myeloid-associated markers, usually CD13, CD117, and CD33. CD7 expression is reported in approximately 40% of AML-M0 cases. In 2016, the WHO noted that expression of a single, relatively nonspecific myeloid-associated antigen, especially by only some blasts and along with other markers of primitive cells (e.g., CD7, CD34, and HLA-DR), is more typical of AUL than AML-M0. There is still another subtype of leukaemia that may be confused with AUL-acute leukaemia of ambiguous lineage, not otherwise specified (NOS) in which combinations of markers that do not allow for their classification as AUL are expressed. In AUL, no more than one membrane marker for any given lineage is typically expressed. Hence, if a given lineage expresses more than one marker, a diagnosis of acute leukaemias of ambiguous lineage, NOS, would be appropriate.
Myeloid sarcoma is a type of myeloid neoplasm in which myeloid tumour cells invade the extramedullary tissues and destroy the original tissue structure to form a mass(4). It can occur independently of AML, concomitantly with AML, and after bone marrow remission(5). Myeloid sarcoma is common in AML-M0, AML-M4 and AML-M5. Myeloid sarcoma can affect any site of the body, most often involving the skin, lymph nodes, gastrointestinal tract, bone, soft tissue and testes(6). Myeloid sarcoma usually expresses myeloid tumour-related markers, though undifferentiated myeloid sarcoma is rarely seen. In 1995, Tosi et al. reported a case of epidural undifferentiated granulocytic sarcoma that occurred before acute promyelocytic leukaemia, which was cured by treatment with all-trans retinoic acid, but the case was not truly undifferentiated due to a lack of flow cytometry immunophenotyping(7). In our case, lymph node puncture and flow cytometry and immunohistochemistry were performed. Flow cytometry confirmed that tumour cells from the lymph nodes had the same immunophenotype as leukaemia cells from the bone marrow, indicating that the tumour cells from the lymph nodes were the same as the leukaemia cells from the bone marrow of this patient. Immunohistochemistry results were also consistent with FCM results. Combined with the bone marrow immunophenotype, this case was consistent with acute undifferentiated leukaemia, indicating undifferentiated myeloid sarcoma in the affected lymph nodes.