急性髓细胞性白血病M2型所致皮肤白血病一例

报道1 例急性髓细胞性皮肤白血病.患者男,38岁,因确诊急性粒细胞性白血病1年,躯干部皮疹1个月入院.皮肤科检查:躯干、右额部皮肤散在数十个直径约1～2 cm大小的红色结节及斑块,略高出皮面,触之有明显浸润感,无压痛.骨髓检查及免疫学证实为急性髓细胞性白血病M2型,患病1年后躯干及前额皮肤出现斑块及结节,皮肤组织病理及免疫组化证实为皮肤白血病.白血病短期内出现皮肤、肺、脾、肾、胸腰骶椎多发性浸润,则提示病情急性进展及预后不良.     

Specific cutaneous infiltrates in patients with myelogenous leukemia: A clinicopathologic study of 26 patients with assessment of diagnostic criteria

Background: Few recent studies have analyzed the clinicopathologic features of specific cutaneous manifestations of myelogenous leukemia in a large number of patients. Objective: We characterize the clinical and histopathologic spectrum of specific cutaneous manifestations in acute (AML) and chronic (CML) myelogenous leukemia, ascertain further diagnostic criteria, and examine current prognosis. Methods: Thirty-six lesions of specific cutaneous infiltrates from 26 patients with my-elogenous leukemia (AML: 17 patients; M:F = 1:2.4; mean age: 52.6 years; AML-French-American-British [FAB] classification subtypes:M1 =1, M2 =3, M4 = 8, M5 = 5. CML = 9 patients; M:F = 4.5:1; mean age: 60.6 years) were retrospectively collected for the study. Results: Cutaneous manifestations presented as solitary or multiple reddish to violaceous papules, plaques, and nodules (17 lesions), or as a generalized erythematous maculopapular eruption (9 lesions). Concurrent extramedullary involvement in other peripheral sites (eg, gums, pharynx, orbits) was observed in 10 patients. Histopathologically, lesions revealed nodular/diffuse infiltrates, often with perivascular and periadnexal accentuation, sparing of the upper papillary dermis, and prominent single arraying of neoplastic cells between collagen bundles. Extension to the subcutis was noted in all deep biopsy specimens (26 lesions). Cytomorphologically, medium to large-sized mononuclear cells (myeloblasts and atypical myelocytes) predominated in AML-M1 and M2, whereas M4 and M5 mainly showed small, medium-sized, or large mononuclear cells with slightly eosinophilic cytoplasm and indented, bi-lobular, or kidney-shaped nuclei (atypical monocytoid cells). In CML, either a variable mixture of mature and immature cells of the granulocytic series (myelocytes, metamyelocytes, eosinophilic metamyelocytes, and neutrophils) or a rather monomorphous infiltrate of mononuclear cells were found. Staining for naphthol AS-D chloroacetate-esterase (NASD) was positive in 24 of 36 lesions (66.6%; AML: 16; CML: 8). Immunohistochemical analysis on paraffin sections using a large panel of antibodies (16 lesions: AML: 13; CML: 3) showed strong reactivity for LCA (CD45), lysozyme, myeloperoxidase (MPD), LN2 (CD74), HLA-DR, and MT1 (CD43) in the majority of cases, and variable staining for monocyte/macrophage markers (KP1/CD68, PGM1/CD68, Mac387, Ki-M1p). The neuronal cell adhesion molecule (N-CAM) marker CD56 was reactive in 2 cases of CML, but negative in all cases of AML. MIB1(Ki67) stained 20% to 80% of neoplastic cells. CD34, CD15, CD20, and CD3 were negative in all cases. No correlation between histochemical/immunohistochemical features with type of leukemia or FAB-subtype of AML was observed. All patients with CML and AML with adequate follow-up died within 24 months after onset of skin lesions (mean survival, AML: 7.6 months; CML: 9.4 months). Conclusion: Specific cutaneous lesions in AML and CML show distinctive clinicopathologic features that allow diagnosis in most cases. Immunohistochemistry on routinely fixed, paraffin-embedded tissue sections provides useful adjunctive information. Simultaneous expression of lysozyme, MPD, CD45, CD43, and CD74 militates in favor of a diagnosis of specific cutaneous infiltrate of myelogenous leukemia. Pitfalls in immunohistologic diagnosis mainly include lack of expression of some myeloid markers (lysozyme, MPD), and aberrant expression of T-cell markers (eg, CD45RO). Regardless of type of myelogenous leukemia, onset of specific skin manifestations correlates with an aggressive course and short survival. (J Am Acad Dermatol 1999;40:966-78.)     

Aleukemia cutis: Clinicopathological and molecular investigation of two cases

We describe two cases of acute myeloid leukemia (AML) who presented with cutaneous manifestations. Leukemia cutis (LC) is the cutaneous presentation of any type of leukemia and occurs in 10% to 15% of patients with AML, but cutaneous infiltration of AML rarely precedes the involvement of the bone marrow or peripheral blood and is called “aleukemia cutis.” Our first case presented with facial skin thickening, a manifestation which is known as lionization and his initial clinical diagnosis was nonspecific allergic reaction. Our second case presented with urticaria-like lesions with the initial clinical and histomorphologic diagnoses of leukocytoclastic vasculitis. Histopathologic examination of skin biopsy specimens in both patients showed diffuse infiltration of the dermis with a monotonous population of intermediate-sized mononuclear cells by open chromatin and promonocytic features. Bone marrow aspiration leukocyte karyotyping showed normal cytogenetics, and molecular investigation revealed mutations of NPM1 and FLT3 genes. Somatic CEBPA gene mutation was negative in both patients. LC as the first manifestation of leukemia is very rare and could result in delayed diagnosis and affect patient prognosis.     

Clinicopathologic correlations in leukemia cutis

This clinicopathologic study involved 42 cases of leukemia cutis: 3 of acute lymphocytic leukemia (ALL), 16 of chronic lymphocytic leukemia (CLL), 12 of acute granulocytic leukemia (AGL), 3 of chronic granulocytic leukemia (CGL), 5 of acute monocytic leukemia (AML), and 3 of acute myelomonocytic leukemia (AMML). The clinical appearance of leukemia cutis included papules, macules, plaques, nodules, ecchymoses, palpable purpura, and ulcerative lesions, and these were seen in all types of leukemias. Gingival hypertrophy was seen only in AML or AMML, and erythroderma and bullous lesions of leukemic infiltration were observed only in CLL. Cutaneous leukemic lesions may be concomitant with or preceding the diagnosis of systemic leukemia. Therefore, skin biopsy may be helpful in detecting the leukemia and may facilitate the work-up. Leukemia cutis probably is a dissemination of systemic leukemia to the skin, and the demonstration of leukemia in skin is associated with a very poor prognosis.     

Leukemia cutis presenting as localized cutaneous hyperpigmentation

The usual clinical presentations of leukemia cutis include solitary infiltrated erythematous or violaceous plaques or nodules and multiple localized or generalized papules. On the other hand, cutaneous hyperpigmentation is a frequent finding in patients with malignancies, most of the cases because of chemotherapy or other drugs that the patient is taking. We present a case of cutaneous hyperpigmentation as the presenting sign of leukemia cutis. A 61-year-old male presented with cutaneous hyperpigmentation, which had appeared during the last chemotherapy cycle for treatment for biphenotypic leukemia. Cutaneous lesions consisted of bluish to brownish irregular well-defined discoloration of the skin involving the upper part of the trunk and the temporal regions of the forehead. The patient was asymptomatic and the skin was not infiltrated at all. However, histopathologic study showed nodular infiltrates involving the full-thickness of the dermis and destroying pre-existing adnexa. This infiltrate was composed of atypical basophilic cells with large hyperchromatic nuclei and scant cytoplasm. Immunohistochemical studies showed intense immunoexpression for CD43, CD68, CD45RO and myeloperoxidase within these cells. A diagnosis of biphenotypic leukemia cutis was established. In our review of the literature we have not found any report of cutaneous hyperpigmentation as the presenting manifestation of leukemia cutis.     

急性髓细胞性白血病(M4型)

报告1例急性髓细胞性皮肤白血病(M4型).患者女,48岁.全身出现丘疹、红色结节14d,伴剧烈瘙痒.体格检查:全身泛发大小不等的红色丘疹、结节,质韧,无压痛.皮损组织病理检查:真皮内弥漫淋巴样细胞浸润,有明显异形及较多核分裂象.免疫组化组织病理检查:CD68阳性(灶性),MPO阳性(少量).骨髓穿刺:白血病细胞大量增生,免疫标记:CD68、CD11b、MPO及HLA-DR均阳性.诊断:急性髓细胞性白血病(M4型).患者经过2次DA(伊达比星、阿糖胞苷)方案化疗后,再次行骨髓穿刺示缓解,但皮损仍有复发.     

Sweet's syndrome in the setting of CD34-positive acute myelogenous leukemia treated with granulocyte colony stimulating factor: evidence for a clonal neutrophilic dermatosis

BACKGROUND: Sweet's syndrome in the setting of hematologic dyscrasias can be categorized into paraneoplastic-associated SS, drug-induced SS, and SS with leukemia cutis. Apart from those cases demonstrating concomitant leukemic infiltrates, it has been surmised that SS is a reactive phenomenon induced by a specific cytokine milieu. METHODS: The authors present a patient with CD34+ acute myelogenous leukemia (AAML) who developed SS in the setting granulocyte colony stimulating factor (GCSF) therapy. Routine light microscopy and molecular studies were carried on the patient's skin biopsy specimen and post-treatment marrow. An X inactivation assay for clonality was employed. RESULTS: Routine light microscopic examination revealed differentiated myeloid precursors including myelocytes and metamyelocytes within the subcutis; myeloblasts were not identified. In addition, in the overlying skin, features typical of SS were observed. The neutrophils demonstrated dysplastic features including hypolobation compatible with a Pseudo Pelger-Huet anomaly. X inactivation studies showed clonality both within her post-treatment marrow and skin biopsy specimen. CONCLUSIONS: Sweet's syndrome developing in CD34+ AML patients following GCSF therapy likely reflects therapy induced differentiation of sequestered leukemic cells, hence indicative of a clonal neutrophilic dermatosis.     

Cutaneous presentation preceding acute myeloid leukemia with CD4+/CD56+ expression misdiagnosed as a blastic plasmocytoid dendritic cell neoplasm: A case report

Acute myeloid leukemia (AML) may initially present as cutaneous lesions corresponding to blasts involving the skin as the first clinical manifestation prior to blood and bone marrow (BM) infiltration. Such presentation is known as myeloid leukemia cutis (LC). Blastic plasmocytoid dendritic cell neoplasm (BPDCN) is an aggressive tumor derived from the precursors of plasmocytoid dendritic cells with cutaneous and BM involvement and leukemic dissemination. Myeloid LC and BPDCN may be difficult to distinguish as they share similar clinical and histopathological features, in particular AML with monocytic differentiation. Nevertheless, the correct diagnosis has to be made to determine adequate and effective therapy. Here, we report the case of a 61‐year‐old woman who presented with an AML with MLL rearrangement and CD4+/CD56+ expression presenting as LC and that was misdiagnosed as BPDCN. We emphasize that careful and exhaustive analyses should be performed to make the correct diagnosis.     

De novo myeloid sarcoma in a 4‐month‐old infant: a case report and review of the literature

Myeloid sarcoma is a rare tumor of immature myeloid cells in an extramedullary site. Myeloid sarcoma may present in a variety of locations; skin is one of the common sites. It may precede or occur concurrently with acute myeloid leukemia, chronic myeloid leukemia, other forms of myeloproliferative disorders/myelodysplastic syndrome or de novo. We report a case of a 4‐month‐old female who presented with cutaneous lesions without evidence of leukemia, determined to be de novo myeloid sarcoma. She had erythematous nodules in multiple skin sites. Biopsy revealed a diffuse atypical mononuclear cell infiltrate involving the entire dermis and extending to the subcutis. The infiltrate was diffusely positive for lysozyme, CD43, CD15, CD33, CD68 and CD117 and was negative for CD3, CD20, CD34, CD56, CD79a, CD99, myeloperoxidase, desmin, chromogranin and synaptophysin, supporting a diagnosis of myeloid sarcoma. No leukemic involvement was found on evaluation of peripheral blood or bone marrow aspiration. Chromosomal abnormalities were found at chromosomes 7, 10 and 11. The skin lesions resolved following multiple chemotherapy courses, then recurred requiring additional treatment. De novo myeloid sarcoma involving skin without evidence of leukemia can occur in an infant and may present a diagnostic challenge.     

以皮疹为首发的急性单核细胞性白血病四例

【摘要】 目的 探讨急性单核细胞性皮肤白血病的临床病理特征。 方法 回顾分析4例以皮肤表现为首发症状的急性单核细胞性白血病患者。 结果 患者均为老年人,年龄分别为68、70、74、82岁。皮疹多表现为淡红色至紫色,质韧的丘疹、结节、斑块,多见于躯干和四肢。无明显自觉症状。皮损组织病理：真皮内大量肿瘤细胞密集、弥漫浸润。肿瘤细胞不亲表皮,与表皮形成明显无浸润带。可见肿瘤细胞围绕血管和附属器结构呈同心层状排列或排列成单行穿梭于胶原纤维束间。肿瘤细胞中等大小,肾形或卵圆形,异形性明显。免疫组化染色结果：肿瘤细胞CD68、CD4、CD45RO、CD56、白细胞共同抗原（LCA）阳性;CD3、CD20、CD30、CD34、CD117,CD123阴性。 结论 该病多见于老年人,组织病理表现为真皮全层胶原纤维间密集均匀一致的肿瘤样细胞浸润,与表皮间存在无浸润带。     

Myeloid leukemia cutis in the setting of myelodysplastic syndrome: a crucial dermatological diagnosis

Cutaneous involvement by myeloid leukemic cells is an unusual phenomenon. Clinical manifestations vary from erythematous papules to plum-colored plaques and nodules that may become purpuric and ulcerate. The definitive diagnosis of myeloid leukemia cutis requires the analysis of biopsy specimens using immunohistochemical staining to determine the expression of selective cell surface markers. We will review myeloid leukemia when first evident in the skin, particularly in the setting of myelodysplastic syndrome. The diagnosis of leukemia cutis in patients with myelodysplastic syndrome is indicative of concomitant or impending acute leukemic transformation. The early recognition and accurate identification of leukemic skin infiltrates in myelodysplastic patients is crucial, as this finding can have significant therapeutic and prognostic implications.     

The spectrum of cutaneous disease in leukemias

Cutaneous eruptions are frequent complications in the clinical course of patients with leukemia. Leukemia cutis is occasionally the cause of the eruption, but in many cases the lesions are non-leukemic. We have retrospectively selected all skin biopsies from patients with a computer-coded diagnosis of leukemia seen in the Stanford University Department of Pathology in the last 7 years, and separated these cases into the broad categories of acute myelogenous leukemia (AML), acute lymphocytic leukemia (ALL), chronic myelogenous leukemia (CML), and chronic lymphocytic leukemia (CLL). We also analyzed separately those cases seen in patients treated with bone marrow transplantation from those treated with standard chemotherapy regimens. We found that leukemia cutis was seen frequently as the cause of lesions in patients with CML and CLL. In contrast, a wide variety of lesions were seen in patients with AML, including a greater number of infectious lesions, drug reactions, vasculitis, and lesions secondary to a hemorrhagic diathesis. In the bone marrow transplantation patients, graft vs host disease was usually the cause of skin lesions in those transplanted for CML and ALL, but again those patients with an underlying diagnosis of AML showed a wide variety of lesions including drug reactions, fungal infections and leukemia cutis. Finally, 6% of cases from patients with AML showed intraepidermal blistering disorders of various types, an association that has not been previously reported.     

A Case of Congenital Leukemia Cutis

Congenital leukemia is a rare disease that develops from birth to 6 weeks of life. Leukemia cutis involves cutaneous infiltration by leukemic cells and is an unusual manifestation of leukemia, and has been documented in 25~30% of patients with congenital leukemia. The authors report a case of congenital leukemia cutis. A newborn male presented with widespread firm dusky red papules and nodules on almost his entire body surface. Skin biopsy specimens confirmed the presence of leukemic infiltrations, and bone marrow cytology was consistent with acute myeloid leukemia of the FAB M5 type.     

Value of immunohistochemistry in the diagnosis of leukemia cutis: study of 54 cases using paraffin-section markers

A grave prognosis is usually associated with leukemic skin infiltrates (leukemia cutis). However, some leukemic skin infiltrates are clinically similar to reactive non-leukemic infiltrates in patients with leukemia; thus it is of great importance to distinguish them. Fifty-four cases which were thought clinically to be leukemia cutis underwent immunophenotyping with a panel of nine T, B, monocytic, and macrophage markers using paraffin sections. Immunohistochemistry helped identify 44 cases with leukemia cutis and 10 with reactive infiltrates. In all cases of leukemia cutis, the staining patterns of skin infiltrates were concordant with cell type in the bone marrow. Furthermore, the panel of markers was usually helpful in distinguishing reactive from leukemia infiltrates, especially in cases with chronic lymphatic leukemia. Immunohistochemistry is a valuable adjunct in histopathologic differentiation of skin infiltrates in most cases of leukemia. With formalin-fixed, paraffin-embedded biopsies, we recommend that CD45 (LCA), CD45RO (UCHL-1), CD3, CD20 (L-26), CD43 (Leu-22), CD68 (KP-1), lysozyme, and chloroacetate esterase be considered in cases of systemic leukemia with cutaneous papules and nodules that prove difficult to interpret with routine section.     

Specific cutaneous infiltrates of B-cell chronic lymphocytic leukemia (B-CLL) at sites typical for Borrelia burgdorferi infection

BACKGROUND: Cutaneous manifestations of B-cell chronic lymphocytic leukemia (B-CLL) comprise a wide spectrum of clinicopathologic presentations. In some cases, onset of skin lesions is triggered by antigenic stimulation, and specific skin infiltrates at sites of previous herpes simplex or herpes zoster infection have been well documented. Specific skin manifestations of B-CLL can also be observed at sites typical for lymphadenosis benigna cutis (nipple, scrotum, earlobe), a Borrelia burgdorferi-associated cutaneous B-cell pseudolymphoma. METHODS: We studied specific skin manifestations of B-CLL arising at sites typical for B. burgdorferi-induced lymphadenosis benigna cutis, analyzing tissues for presence of B. burgdorferi DNA using the polymerase chain reaction (PCR) technique. Six patients with B-CLL (M : F = 4 : 2; mean age: 67.8) presented with specific skin lesions located on the nipple (four cases) and scrotum (two cases). RESULTS: Clinically there were solitary erythematous plaques or nodules. Histology revealed in all cases a dense, monomorphous infiltrate of small lymphocytes showing an aberrant CD20+/CD43+ phenotype. In all cases monoclonality was demonstrated by PCR analysis of the JH gene rearrangement. PCR analysis showed in four of the six cases the presence of DNA sequences specific for B.burgdorferi. CONCLUSIONS: Our study demonstrates that infection with B. burgdorferi can trigger the development of specific cutaneous infiltrates in patients with B-CLL.     

Leukemic vasculitis: a rare pattern of leukemia cutis

Although non‐specific skin lesions are quite common in patients with leukemia, the specific infiltration of the skin by blast cells, known as leukemia cutis, is rare. Its incidence ranges from 1 to 50% and depends on the specific type of leukemia. Leukemic vasculitis represents a rare form of leukemia cutis consisting of the involvement and destruction of vessel walls by leukemic cells, which in themselves cause the vascular injury. To date, only few cases of leukemic vasculitis have been described. Here, we report two cases of this rare skin condition, one of which mimicked cutaneous polyarteritis nodosa. Cañueto J, Meseguer‐Yebra C, Román‐Curto C, Santos‐Briz A, Fernández‐López E, Fraile C, Unamuno P. Leukemic vasculitis: a rare pattern of leukemia cutis.     

Trisomy 8 in myeloid leukemia cutis confirmed by fluorescence in situ hybridization analysis

We present a case of a 64‐year‐old man with refractory acute myeloid leukemia and trisomy 8 who developed leukemia cutis. Interphase fluorescence in situ hybridization (FISH) was performed on a paraffin‐embedded skin section. FISH confirmed a population of cells with trisomy 8 in the blastic infiltrates involving the skin. This case illustrates a novel application of interphase FISH to confirm the diagnosis of leukemia cutis.     

Aleukemic leukemia cutis

Aleukemic leukemia cutis has always been a dermatological curiosity. It is a rare condition characterized by the infiltration of skin by leukemic cells before their appearance in the peripheral blood or bone marrow. A 20 year old man had presented with nodular swelling on the scalp of 6 months duration along with cervical lymphadenopathy. Biopsy and immunohistochemistry revealed myeloid sarcoma. The initial presentation was aleukemic and repeated peripheral blood counts and marrow examinations were normal. However, the outcome was fatal within 3 months of diagnosis of cutaneous lesions.     

Differentiation syndrome during ivosidenib treatment with immunohistochemistry showing isocitrate dehydrogenase R132H mutation

We report a case of differentiation syndrome in a patient receiving the IDH1 inhibitor ivosidenib, with skin biopsy showing isocitrate dehydrogenase (IDH) R132H-mutated leukemia cutis. A 72-year-old man with IDH1-mutated acute myeloid leukemia (AML), status-post allogeneic cell transplantation, on ivosidenib for 6 months, was admitted for culture-negative neutropenic fever, pink and purpuric plaques and patches on the legs, abdomen and back, edema, hypotension, and shortness of breath. Skin biopsy revealed an infiltrate of atypical, immature, myeloperoxidase-positive mononuclear cells compatible with leukemia cutis or Sweet syndrome. Although dermal edema and interstitial neutrophilic infiltrate with karyorrhexis characteristic of Sweet syndrome were not seen, the atypical cells lacked expression of CD117 and CD34, which were expressed in the original leukemia. Additional immunohistochemical staining of suspected blasts was strongly positive for IDH1 R132H, suggesting a diagnosis of leukemia cutis. As the immunophenotype of blasts in skin infiltrates can significantly differ from the immunophenotype seen in blood and bone marrow, this case shows that mutation-specific antibodies such as anti-IDH1 R132H may be useful to help distinguish malignant from non-malignant infiltrates in the skin. Furthermore, differentiation syndrome may show histopathologic features of leukemia cutis on skin biopsy.     

Leucemia cutánea aleucémica: presentación de un caso

—The term aleukemic leukemia cutis describes the invasion of the skin by leukemic cells in the absence of peripheral blood and/or bone marrow involvement. Although the pathogenic mechanisms of this disease are still unknown, it is widely recognized its poor prognosis. Most of the reported patients completely developed the hematologic disease (the majority acute granulocytic or monocytic leukemias) in 10-14 months after diagnosis of aleukemic leukemia cutis, and they had a median survival of 22 months.We report on a case of a 77-year-old man with aleukemic leukemia cutis who presented with numerous erythematous to violaceous papulonodular lesions, mainly located on the trunk and head, lack of peripheal blood involvement and very early alterations in the bone marrow aspirate. Inmunohistochemical stains of skin and bone marrow biopsies revealed the infiltration of both tissues by blast cells of monocyte-histiocytic lineage. Our patient presented spontaneous resolution of skin lesions and his hematological disease showed no progression during 9 months after diagnosis, although he did not undergo any treatment.We emphasize the low incidence of association between myelodysplastic syndromes and aleukemic leukemia cutis as well as the surprising spontaneous remission of cutaneous lesions in our patient.