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Cutaneous infiltrate of chronic lymphocytic leukemia and relationship to primary cutaneous epithelial neoplasms.

Chronic lymphocytic leukemia involves the skin in a small percentage of patients and may portend an ominous prognosis in some patients. We report a series of eight biopsies from seven different patients in which the cutaneous leukemic infiltrate was confined exclusively to the region immediately surrounding primary epithelial neoplasms including squamous cell carcinoma (6), basal cell carcinoma (1) and actinic keratosis (1). The malignant lymphocytes appear to constitute a host response to these neoplasms and do not appear to suggest a rapid downhill course for these patients. These observations serve to 1) suggest a new pattern of cutaneous involvement by leukemic cells and 2) offer some insights into potential cellular trafficking patterns of these neoplastic cells.

Aged↗

Optic nerve involvement in acute lymphoblastic leukemia.

Leukemic infiltration of the optic nerve is rare. We describe the diagnostic assessment and the outcome in two adult patients suffering from acute lymphoblastic leukemia with T phenotype. In both cases the leukemic involvement of the eye was observed as an isolated extramedullary relapse followed after several months by hematological relapse. CT and MRI scans were negative, while an A-scan echography of the eye clarified the diagnosis. Early radiotherapy caused recovery of visual acuity in one case. A-scan echography is the most sensitive investigation for the early recognition of ocular localization in acute leukemias.

Adult↗

Successfully treated optic nerve infiltration with adult T-cell lymphoma.

A 45-year-old woman with adult T-cell leukemia had a sudden onset of decreased vision with central scotoma in the right eye. Right optic disc edema and thickening of the optic nerve were observed by magnetic resonance imaging. A diagnosis of leukemic infiltration to the optic nerve was made. A course of oral corticosteroid therapy was prescribed and 40 Gy of radiation was administered to the whole brain and right orbit. Her visual acuity recovered from finger counting to 20/20 within 3 weeks. We believe that this patient represents the first report of successfully treated optic nerve infiltration with adult T-cell leukemia caused by human T-lymphotropic virus type-I infection.

Female↗

[Anterior segment of the eye and cranial nervous (II, III, VI, VII) infiltration in relapsing acute lymphoblastic leukemia (L1)].

A 42-year-old male was admitted with nasal bleeding. On admission he showed no abnormal neurological sign. A diagnosis of acute lymphoblastic leukemia (ALL) (L1) was made, and modified L-10M protocol was performed. During consolidation chemotherapy, the bone marrow was in remission but he showed left facial palsy. Four days after the onset of left facial palsy, the patient developed bilateral facial palsy followed by left oculomotor and abducens nerve palsy. At this time, bilateral ocular fundus showed papilloedema, exudate, bleeding, Roth's spot and leukemic infiltration to the anterior segment of the eye. Systemic chemotherapy with intrathecal injection of anti-leukemic drugs and whole brain irradiation was partially successful against cranial nervous system (CNS) complaints, but the patient relapsed. Seven month later hypopyon and secondary glaucoma developed and trabeculectomy was performed. The bone marrow revealed an increase of leukemic blasts. Chemotherapy consisting of various drugs was not effective, and he died of pneumonia. In this case, although intrathecal chemotherapy and whole brain irradiation were attempted, leukemia evolved CNS, retina and uvea despite the fact that the bone marrow was in complete remission, allowing various cranial nerve signs and ocular manifestations to occur.

Abducens Nerve↗

Isolated ocular relapse in childhood acute lymphoblastic leukemia during continuing complete remission.

Leukemic relapse of the eye has sometimes been cured. In this paper we review the cases of leukemic infiltration of the eye tissue with the aim of ascertaining whether an optimal treatment can be suggested. Data from 25 children (16 males, 9 females) with isolated ocular relapse (10 in therapy, 15 off therapy) of acute lymphoblastic leukemia (ALL) in first complete remission are examined. The patients were treated according to different chemotherapy schedules, with (20 pts) or without local radiotherapy (5 pts). Isolated ocular relapse can be successfully treated, especially if it occurs after the withdrawal of therapy; second ocular infiltration was seen only in anterior chamber involvement after low doses of local radiotherapy. While the need for high doses of chemotherapy is not evident, high doses of ocular radiotherapy (> 20 Gy) seem to be mandatory to cure this leukemic relapse.

Adolescent↗

Leukemia cutis in congenital leukemia. Analysis and review of the world literature with report of an additional case.

BACKGROUND: Congenital leukemia cutis is rarely reported in the dermatology literature despite various authors citing 50% of infants with congenital leukemia have skin involvement. These seemingly disparate facts prompted a review of the world literature that was performed by searching the MEDLINE database from 1966 up to and through December 1992, reviewing Index Medicus for the years prior to computerized MEDLINE search, and reviewing appropriate case report references. OBSERVATIONS: A 2-month premature male infant was born with 182 x 10(9)/L circulating monoblasts, prominent hepatosplenomegaly, and multiple firm blue and red cutaneous nodules. CONCLUSION: Approximately 175 cases of congenital leukemia have been reported with at least 41 and possibly 56 cases identified with leukemia cutis. Specific cutaneous leukemic infiltrates occur in 25% to 30% of infants with congenital leukemia and usually appear as firm blue, red, or purple nodules in a generalized distribution. In contrast to the 50% incidence of gingival and oral infiltrates reported in adult monocytic leukemia, only 1% of congenital leukemia patients have oral involvement. Congenital leukemia cutis may precede other manifestations of leukemia by as much as 4 months. Whereas leukemia cutis is associated with a poor prognosis in adult leukemics, the natural history of congenital leukemia is not altered by leukemia cutis.

Humans↗

Specific skin infiltration as first sign of chronic myelomonocytic leukemia with an unusual phenotype.

A patient who had a plaque on his forehead as the first sign of chronic myelomonocytic leukemia (CMML) is described. Histologic studies, which formerly led to the misdiagnosis of non-Hodgkin's lymphoma, revealed CMML with an unusual phenotype. This represents a rare type of CMML for the following reasons: (1) specific cutaneous involvement is rarely the first sign of CMML; (2) the unique phenotype was detected by immunohistology on lesional skin, specifically, the leukemic infiltrate was CD4-positive and notably negative for CD15, the pan myeloid/monocytic marker.

Aged↗

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.

Adolescent↗

Mixed-lineage acute myeloid leukemia associated with a suprasellar dysgerminoma.

An association between primary mediastinal germ cell tumors and hematologic malignancies has been recognized since 1985. We present a patient with a suprasellar germ cell tumor and an associated leukemia. A 20-year-old black female presented in December 1987 with a 6-month history of headaches and weight loss, confusion, polyuria, and polydipsia. Evaluation revealed hypernatremia, normal neurologic examination except poor recall, and an enhancing inhomogeneous suprasellar mass on cranial computed tomography. Biopsy of the mass diagnosed a dysgerminoma, which was treated with craniospinal radiation. In February 1988, the patient developed pancytopenia, which resolved with discontinuation of cimetidine and phenytoin. She did well until June 1988 when she presented with skin lesions over the trunk and extremities. Skin biopsy revealed a leukemic infiltration. She was admitted with a WBC 1,500/microliter (without blasts), Hb 11.6 g/dl, PLT 210,000 microliter. Bone marrow biopsy revealed hypercellularity with 50% blasts, demonstrating mixed-lineage acute myeloblastic leukemia (myelomonocytic-M4; megakaryoblastic-M7). The patient was induced with a standard Ara-C/daunorubicin regimen. Two weeks postinduction, she became septic and expired. An autopsy demonstrated leukemic involvement of the spleen, liver, bone marrow, and skin, without residual dysgerminoma. This represents the first reported case of suprasellar dysgerminoma associated with a mixed-lineage leukemia not related to chemotherapy.

Adult↗

Hemiballismus in patient with blastic phase of chronic myelogenous leukemia.

The authors report the clinical course and neuropathological findings in the case of hemiballismus due to leukemic infiltration of the subthalamic nucleus. The symptoms were observed in a 19-year-old patient with blastic phase of chronic myelogenous leukemia, two weeks before death, when what is called the "critical point" developed (white cell count beyond 100 G/l and thrombocytopenia less than 50 G/l). The investigation are considered to confirm the role of the "critical point" in the development of central nervous system leukemic complications.

Adult↗

[Extramedullary (bone) relapse 16 months after allo bmt in a 7-year-old girl treated for acute lymphoblastic leukaemia from the second year of life].

7-year-old girl treated for acute lymphoblastic leukaemia since June 1995 after marrow relapse (June 1997) presented with painful oedema of the upper part of left hip and limping, 16 months after allogeneic bone marrow transplantation (BMT). Bone marrow examination excluded medullary relapse. Histopathological investigation of periosteum and bone scrapings revealed massive leukemic infiltration. Radiotherapy resulted in local arrest of the malignant process. However, bone marrow relapse was diagnosed in the child two months later with subsequent death after one month.

Bone Marrow Transplantation↗

Acute basophilic leukemia presenting with abnormal liver function tests and the absence of blast cells in the peripheral blood.

Acute basophilic leukemia is an uncommon form of acute leukemia, rarely occurring as a de novo disease. We describe a case of de novo acute basophilic leukemia occurring in a 47-year-old man who presented with abnormal liver function tests in the absence of leukemic infiltration of the liver. We postulate that this presentation occurred as a consequence of pathophysiological features of the malignant basophilic blast cells.

Antineoplastic Combined Chemotherapy Protocols↗

CD56+ blastic transformation of chronic myeloid leukemia involving the skin.

We report on two patients with chronic myeloid leukemia (CML) who presented blastic transformation involving the skin, with leukemic infiltrates showing unusual morphologic and immunohistologic characteristics. Both patients were elderly men with a 36-month and a 40-month history of CML, respectively. They presented with disseminated, reddish to violaceous papules and plaques (case 1), and with localized reddish nodules on the left temporal area (case 2). Concurrent features of blastic transformation in the bone marrow were observed in one patient (case 1). Histopathologic examination of skin lesions revealed similar features in both cases. There was a moderate to dense dermal infiltrate composed mainly of medium-sized atypical mononuclear myeloid precursor cells with only few relatively well-differentiated cells of the granulocytic series. Histochemical staining for naphthol-ASD-chloroacetate esterase revealed strong positivity (>50% of neoplastic cells) in case 2 and only scattered positivity (< 10% of neoplastic cells) in case 1. Immunohistologic analysis performed on paraffin-embedded sections showed in both cases variable reactivity of neoplastic cells for leucocyte common antigen (CD45), lysozyme, myeloperoxidase, CD11c, CD15, CD43, CD66, CD68, HLA-DR, and the neural cell adhesion molecule (NCAM) CD56. A negative reaction was observed for CD3, CD34, and TdT. The immunohistologic findings were remarkably similar to those reported for acute myeloid leukemia (AML) with monocytic differentiation (French-American-British [FAB] classification, subtype M4). Examination of blasts from the bone marrow performed in one patient (case 1) revealed a similar phenotype also with CD56 expression. In conclusion, our observations show that specific cutaneous infiltrates in CML may show morphologic and immunohistochemical characteristics similar to those observed in AML with monocytic differentiation. Moreover, specific cutaneous manifestations of CML may express CD56.

Aged↗

Relapse of acute lymphoblastic leukemia in the inferior rectus muscle of the eye.

BACKGROUND: Extramedullary involvement of acute lymphoblastic leukemia (ALL) in sites outside the central nervous system (CNS) or testes is rare and may signal a refractory form of leukemia. METHODS: The authors describe a child with ALL who experienced a relapse involving the inferior rectus muscle of the eye. This patient had been treated with a bone marrow transplant for previous bone marrow and ovarian relapse. RESULTS: The patients had a pre-B ALL with a t(1;19) chromosomal translocation and previously had experienced relapse during therapy. At the time of the muscle relapse, she had pancreatomegaly consistent with leukemic infiltration but no CNS or bone marrow disease. CONCLUSIONS: Relapse of ALL in unusual sites may indicate disease that is particularly difficult to eradicate. Factors in addition to age and leukocyte count at diagnosis determined risk. Additional research is needed to define these factors and develop more effective therapy.

Child, Preschool↗

Good engraftment of B-cell precursor ALL in NOD-SCID mice.

BACKGROUND: In vivo models for human B cell precursor ALL have been established by transplanting human leukemic cells onto immune-deficient SCID mice. High risk and relapsed leukemias engraft very well in these mice, however, good prognosis pediatric ALL often grow poorly if at all. Recently a new, even more immune-deficient mouse strain has been bred by crossing the scid mutation onto the NOD mouse background. As these NOD-SCID mice have been shown to be better recipients for human myeloid cells the goal of this study was to test these mice as hosts for human acute lymphoblastic leukemia cells. PATIENTS AND METHODS: Bone marrow or peripheral blood cells from/pediatric and one adult patient with B-cell precursor ALL were transplanted onto immune-deficient NOD-SCID mice according to established protocols. MAIN RESULTS: ALL cells from 6 out of the 8 patients (75%) successfully engrafted the NOD-SCID mice and from 4 patients (50%) led to an extensive leukemic infiltration in the murine marrow (> 10%). High level human cell engraftment could be demonstrated by flow cytometry, Southern blot analysis and cytology. By cytology and immunophenotype the leukemia in the mice was indistinguishable from the original leukemia in the patients. The presence of few human eosinophils in the marrow of highly engrafted mice indicates minimal coengraftment of residual normal cells. Development of overt leukemia in the mice after transplantation of cells from different patients varied between 1.5 and 7 months. Interestingly and in contrast to myeloid cells, conditioning of the mice by sublethal irradiation was not necessary for successful engraftment. Limiting dilution experiments with leukemic blasts from one patient showed that as few as 10000 cells were sufficient to transfer the leukemia onto NOD-SCID mice. CONCLUSIONS: NOD-SCID mice are sensitive recipients for human ALL xenografts.

Adult↗

Neurologic complications of leukemia.

PURPOSE OF REVIEW: As treatment of the leukemias improves, patients are surviving longer. Recognizing and rapidly treating metastatic complications or avoiding neurotoxic therapies improves outcome, reduces morbidity and mortality, and limits long-term sequelae. RECENT FINDINGS: Neurologic dysfunction may result from leukemic infiltration of the nervous system or as a consequence of chemotherapy or prophylactic craniospinal irradiation. The present review summarizes common problems in the neurologic complications of leukemia and discusses recent advancements in their diagnosis and treatment. SUMMARY: Topics covered in detail include central nervous system prophylaxis, leptomeningeal metastasis, and common hematologic complications affecting the brain. The findings aid in the clinical management of patients with leukemia.

Blood Viscosity↗

Case report: central neurocytoma with concomitant cerebral involvement by acute lymphatic leukemia.

Central neurocytomas are intraventricular tumors composed of round uniform cells. These tumors have usually favorable prognosis. Leukemic infiltrates are occasionally seen as a complication of acute lymphatic leukemia. This report describes a 7-year-old boy who was treated because of diagnosed lymphatic leukemia with central nervous system involvement and concomitant neurocytic tumor located in the fourth ventricle. These two entities might be problematic to differentiate from each other without proper histopathological examination.

Biomarkers, Tumor↗

Vaginal obliteration after total body irradiation and chemotherapy as treatment for acute myeloid leukemia.

Although radiotherapy is an integral part in the management of certain types of hematological malignancies, its effect on the reproductive system has been well documented. We report a rare complication where a patient had complete vaginal obliteration after receiving a dose of total body irradiation (1575 cGy) as part of her treatment for acute myeloid leukemia. A 37-year-old married woman, G3P2, underwent high-dose cyclophosphamide accompanied by high dose (1575 cGy) total body irradiation (TBI) as part of her treatment for acute myeloid leukemia (AML: m1) when she was 35 years of age. After TBI, the patient developed ovarian failure and amenorrhea, which was confirmed by hormonal evaluation. Nevertheless, she did not receive any hormonal replacement therapy and stopped her sexual life for two years. Fortunately, no recurrence of AML was noted. The patient visited our clinic due to difficulty in performing coitus. Physical examination showed a 2-cm short and blinded vaginal pouch. She initially received hormonal replacement therapy followed by surgical correction via vaginoplasty and two months of dilatory replacement and frequent coitus with satisfactory result. To our limited knowledge, vaginal obliteration as a complication of condition regimen has never been reported before. In the present case report, it is unclear whether spontaneous vaginal obliteration resulted from chemotherapy, total body irradiation, or another unknown cause such as a concomitant leukemic infiltration of the vaginal wall, severe bacterial and fungal infection before treatment, or from any combination of the above. However, due to this case presentation, we suggest that such patients must receive hormonal replacement therapy and be encouraged to have a normal sexual life to avoid this possible problem.

Adult↗