Aleukemic leukemia cutis. An unusual presentation of acute myelomonocytic leukemia

A patient with acute myelomonocytic leukemia is reported. He had presented erythroderma and atypical cellular infiltration of the skin 4 months prior to the detection of leukemia in the peripheral blood and bone marrow. Aleukemic leukemia cutis is a rare condition which is characterized by leukemic cells invading the skin prior to the observation of leukemic cells in the peripheral blood. The cases of aleukemic leukemia cutis reported in the literature show little or no conformity in their clinical appearance. Enzyme cytochemistry, immunocytological and electron-microscopic studies are of considerable help in differentiating the cutaneous infiltrates and in establishing early diagnosis. We report herein a patient with erythroderma which regressed spontaneously, whereas microscopic examination of a cutaneous biopsy showed atypical cells infiltrating the dermis. After a period of 3 months, during which the patient remained free of lesions, he showed recurrence of the erythroderma while developing acute myelomonocytic leukemia. We feel this unusual presentation of aleukemic leukemia cutis should be added to the evergrowing list of cutaneous manifestations of leukemia.     

Leukemia cutis in acute lymphocytic leukemia masquerading as viral exanthem.

Leukemia cutis is a specific skin lesion caused by infiltration of leukemic cells into the skin. It is uncommon in acute lymphocytic leukemia (ALL). It typically manifests as red or violaceous papules, nodules, or plaques, mainly on the face. Leukemia cutis presenting with a generalized viral exanthem-like maculopapular eruption appears to be rare in the English literature. We report such a case. A 19 year-old man presented with a generalized purpuric maculopapular eruption of eight day's duration. Hematologic studies showed changes of acute lymphocytic leukemia, T-cell type. A skin biopsy specimen revealed a cuff-like, dense, perivascular infiltration of atypical lymphocytes in the upper and mid-dermis, consistent with leukemia cutis. The rash resolved in two weeks after chemotherapy. Our case illustrates that leukemia cutis should be considered in the differential diagnosis of a generalized morbilliform viral exanthem-like eruptions. Skin biopsy is important in establishing the diagnosis.     

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.     

Aleukemic leukemia cutis.

Specific leukemic cutaneous infiltrates preceded observable leukemic cells in the blood in a case of acute lymphoblastic leukemia. Examination of a cutaneous biopsy specimen led to early diagnosis of the disease.     

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.     

Leukemia cutis originating in the extravasation site of i.v. gabexate mesilate infusion

Leukemia cutis is a localized or disseminated skin infiltration by leukemic cells. A 64-year-old man was diagnosed with acute myeloid leukemia (AML) complicated by disseminated intravascular coagulation. During the course of treatment with gabexate mesilate, the substance accidentally leaked from the infusion site in his elbow. One month later, a dark red erythema and induration accompanied by severe pain appeared in the area proximal to the gabexate mesilate injection site. The biopsy specimen demonstrated not only inflammation but infiltration of leukemic cells as well. Immunohistochemical staining for intercellular adhesion molecule-1 and platelet/endothelial cell adhesion molecule-1 showed strong expression of endothelial cells and leukemic cells. We speculate that the gabexate mesilate might have played a role in the induction of leukemia cutis via adhesion molecules in our case.     

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.     

Leukemia Cutis in Three Children: Clinical and Immunohistochemical Studies

Abstract: We report 3 children with leukemia cutis observed at the initial diagnosis of systemic leukemia. Leukemia subtypes in the three children were congenital monocytic, acute undifferentiated, and acute monocytic, respectively. The patients were girls age 10 days, 14 years, and 11 months, respectively, at diagnosis. We describe the clinical features of the cases and the results of immunohistochemical studies on paraffin-embedded skin biopsy specimens. The skin lesions were tumors and areas of reddish purple erythema in the first child, pigmented erythema in the second, and bright red erythema in the third. In the first two patients skin lesion biopsy specimens had dense leukemic infiltrates in the dermis with reactive T lymphocytes scattered among them. In the third patient, the infiltrating cells were almost all reactive T lymphocytes, with a few leukemic cells. A relationship between the leukemic-reactive cell ratio and the prognosis was suggested; dense leukemic cell infiltrates may be associated with a poor prognosis.     

Acute myelomonocytic leukemia presenting as a benign-appearing cutaneous eruption

Aleukemic leukemia cutis is a rare condition in which patients have skin lesions containing leukemic cells before evidence of leukemia can be detected in the peripheral blood. There are only 23 cases of this phenomenon documented in the English literature. We describe a 62-year-old woman who developed a diffuse, clinically benign-appearing cutaneous eruption, which histologically showed an atypical infiltrate of cells, 4 months before leukemic cells were found in her peripheral blood and the diagnosis of acute myelomonocytic leukemia was made by bone marrow aspiration. This case illustrates the difficulty in diagnosing leukemia cutis from examination of routine histologic sections and the importance of specialized marker studies in determining the cause of an atypical cellular infiltrate of the skin. It also illustrates how leukemia cutis can masquerade as a clinically benign-appearing cutaneous eruption in a seemingly healthy patient with normal blood parameters.     

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.     

Aleukemic leukemia cutis presenting as benign-appearing exanthema.

Aleukemic leukemia cutis is a rare condition characterized by the infiltration of the skin by leukemic cells before their appearance in the peripheral blood or bone marrow. We report here a 62-year-old seemingly healthy patient who presented with disseminated erythematous maculae. A skin biopsy showed leukemia cutis of monocytic type. No involvement of bone marrow or peripheral blood was found. The patient developed acute monocytic leukemia 7 months later. We present this case to illustrate how leukemia cutis can masquerade as a clinically benign-appearing cutaneous eruption without leukemic changes in blood or bone marrow. To confirm the diagnosis of aleukemic leukemia cutis, immunohistochemistry of the skin lesions as well as a complete staging procedure is necessary.     

Leukemia Cutis in Blastic Transformation of Chronic Myelocytic Leukemia: TdT Positive Blasts and Response to Vincristine and Prednisone

A patient with chronic myelocytic leukemia (CML) in blast transformation with extensive involvement of the skin is reported. The leukemic infiltrates consisted of blasts with lymphoblastoid morphology which were positive for terminal deoxynucleotidyl transferase (TdT) by fluorescent assay. The infiltrates rapidly resolved with vincristine and prednisone therapy. Similar recurrences 4 and 8 months later responded as dramatically to the same therapy and to cytosine arabinoside. This unusual case of extensive leukemia cutis supports the evidence that patients in blast crisis with TdT positive cells are responsive to vincristine and prednisone. The implications of this case in terms of the origin of these cells based upon morphology and TdT content, as well as the diagnosis and therapy, are discussed.     

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 en un paciente con leucemia mieloide aguda M2

—The leukemia cutis is the cutaneous infiltration by leukemics cells. Patients with acute myelogenous leukemia (AML) present specific cutaneous involvement in approximately 10% of the cases.We report the case of a leukemia cutis in a 73-year-old male with AML-M2. The patient presented with a one-week history of general malaise, asthenia, cough, dysnea and fever. Physical examination revealed and indurated red-brown plaque on his back of two moths duration, which was pruritic. Concomitance blood and bone marrow findings were diagnostic of AML-M2. A cutaneous biopsy was consistent with leukemia cutis. A CT and a bronchial biopsy showed pulmonary involvement. Since starting chemotherapy the patient had complete remission and the cutaneous lesion cleared, but 15 days later the skin lesion reappeared. A new bone marrow examination revealed recurrent leukemia. He died one month later.     

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.     

CUTANEOUS INVOLVEMENT IN CHRONIC MYELOMONOCYTIC LEUKEMIA

Background. Chronic myelomonocytic leukemia has been associated with various nonspecific cutaneous manifestations. Rarely has the leukemia been reported to directly affect the skin. Methods. This case documents the progression of a patient who ultimately developed chronic myelomonocytic leukemia, by clinical examination, hematologic parameters, dermatopathology, and bone marrow pathology. Results. The skin showed nonspecific cutaneous involvement, progressing to specific leukemic lesions parallel with increasing systemic and hematologic involvement. Conclusions. Chronic myelomonocytic leukemia can manifest with lesions of leukemia cutis. The possibility of nonspecific cutaneous involvement in the preleukemic phase exists.     

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.     

Leukemia cutis in association With Grover's disease

Grover's disease (GD), or transient acantholytic dermatosis, is a persistent recurrent dermatosis that usually occurs in men older than 50 years. Rare cases of GD and hematologic malignancy in the same cutaneous biopsy specimen have been reported. We report a case of GD in association with leukemia cutis. A 72-year-old man with a history of myelodysplastic syndrome presented with numerous pruritic papules on the torso, which were clinically diagnosed as GD. A skin biopsy revealed foci of suprabasal acantholysis and dyskeratosis consistent with GD and dense aggregates of mononuclear atypical cells in the superficial dermis consistent with leukemia cutis. Direct immunofluorescence was negative. This case illustrates the need to consider a diagnostic skin biopsy in any patient who presents with classic clinical findings of GD if there is any indication that the patient may be at higher risk for a hematologic malignancy.     

Acral localized acquired cutis laxa as presenting sign of underlying systemic amyloidosis

Acral localized acquired cutis laxa (ALACL) is a rare variant of acquired cutis laxa, and the clinical appearance is characterized by loose, redundant and wrinkled skin of the distal extremities. By definition, histopathology of affected tissue reveals sparse or fragmented elastic fibers. However, this can be difficult to assess on routine staining, and sometimes requires electron microscopy. The condition has been associated with plasma cell dyscrasias or recurrent inflammatory states. We present a case of a 65-year-old man who presented with enlarged and doughy finger pads. Skin biopsy showed diffuse dermal amyloid deposition displacing dermal stroma and reduction of elastic fibers, although these changes were subtle on routine hematoxylin and eosin staining. Mass spectrometry of laser capture microdissected tissue showed AL kappa-type amyloid and further workup revealed a diagnosis of primary systemic AL-kappa amyloidosis requiring bone marrow transplantation. This case represents an unusual presentation of acquired cutis laxa and highlights the need for a high index of suspicion when reviewing histopathology of this entity. In addition, the case highlights the importance of investigation into possible systemic associations, such as plasma cell dyscrasias.     

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.