Anaplastic lymphoma kinase-positive primary cutaneous anaplastic large cell lymphoma--is it a new variant?

Anaplastic large cell cutaneous lymphomas are clinically and pathologically heterogeneous, CD30 + (Ki-1) lymphoproliferative disorders. The importance of anaplastic lymphoma kinase (ALK) positivity is well known in the prognosis of primary systemic anaplastic large cell cutaneous lymphomas; however, the same in primary cutaneous anaplastic large cell cutaneous lymphomas is not much clear. Herein we report a 65-year-old male with an 18-month history of minimally pruritic localized nodulo-plaque lesion over lower back. Histology revealed cutaneous large cell lymphoma and immunohistochemical staining showed positivity for CD30, CD3 and ALK. The role of ALK positivity in pcALCL is discussed in this article.     

Myxoid variant of primary cutaneous anaplastic large cell lymphoma: First 2 cases

Anaplastic large cell lymphoma (ALCL) is a CD30+ T‐cell non‐Hodgkin lymphoma with 2 main clinical presentations: primary cutaneous ALCL (pcALCL) and systemic ALCL (sALCL). While rare cases of myxoid sALCL have been reported, there are no previous cases of myxoid pcALCL reported. We present 2 unusual cases of pcALCL showing prominent collections of dermal mucin closely intermingling with the anaplastic lymphocytes. Patient 1 was a 30‐year‐old woman who presented with ulcerated nodules on her neck, abdomen, chest and shoulders. A systemic lymphoma was excluded by physical examination, positron emission tomography and computed tomography (PET‐CT) scan, as well as by bone marrow biopsy and flow cytometry studies. The patient was closely followed‐up for 10 months without evidence of systemic involvement. The biopsy showed diffuse infiltration of the dermis by a CD2+, CD30+, anaplastic lymphoma kinase (ALK)‐negative ALCL. Patient 2 was a 55‐year‐old woman who presented with a single nodule on her right arm. A systemic lymphoma was excluded by physical examination as well as by a PET‐CT scan. The biopsy showed diffuse and dense lymphoid infiltration of the whole biopsy by a CD3+, CD4+, CD30+, ALK‐negative ALCL. The atypical lymphocytes were intermingled with large amounts of dermal stromal mucin.     

Cutaneous presentation on the eyelid of primary, systemic, CD30+, anaplastic lymphoma kinase (ALK)-negative, anaplastic large-cell lymphoma (ALCL)

AIM: To report an unusual case of cutaneous presentation on the eyelid of systemic (or nodal), CD30+, anaplastic large-cell lymphoma (ALCL). METHODS: A 39-year-old man presented with a rapidly growing exophytic mass on the left upper eyelid, with a protuberant, ulcerated aspect and with discharge. The patient showed lymph node involvement 3 months after the appearance of the lesion on the eyelid (the lesion itself appeared 1 week before examination). RESULTS: The histopathologic and immunohistochemical diagnosis was ALCL, T-cell phenotype, strongly positive for CD43 and CD30, and negative for CD3, anaplastic lymphoma kinase (ALK), and B-cell antigens. Treatment was by radiotherapy and, later, chemotherapy (cyclophosphamide, adriamycin, vincristine, and prednisolone, CHOP) for skin recurrences and lymphadenopathies over 5 years. There has been no recurrence for more than 6 years. CONCLUSIONS: Primary, systemic, CD30+, ALK-negative, ALCL presentations generally have a poor prognosis and tend to occur in older individuals, although the clinical outcome is highly variable and difficult to predict in individual cases. Only three cases of ALCL have been described in the ocular adnexae and none was ALK-negative.     

Fatal ALK-negative systemic anaplastic large cell lymphoma presenting with disseminated cutaneous dome-shaped papules and nodules

Anaplastic large cell lymphoma (ALCL) is classified as a CD30 positive non-Hodgkin lymphoma. Systemic ALCL (S-ALCL) is further subdivided into two subgroups based on anaplastic lymphoma kinase (ALK) expression. In systemic ALCL, positive ALK expression correlates with a favorable prognosis, whereas negative ALK expression correlates with poorer overall survival. By definition, primary cutaneous ALCL (cut-ALCL) is limited to the skin and is uniformly ALK-negative. Cut-ALCL closely resembles LyP with regards to its benign clinical course and CD30 positivity. We describe a unique case of ALK-negative (ALK-) S-ALCL presenting with cutaneous disseminated dome-shaped papules.     

间变性淋巴瘤激酶阴性的间变性大细胞淋巴瘤泛发性皮肤侵犯一例

患者男,37岁,入院前7个月无明显诱因右大腿出现一鹅蛋大小肿物,无明显不适,肿物逐渐增大,右大腿、臀部出现弥漫性、非凹陷性肿胀,入院前2个月全身皮肤出现暗红色丘疹、结节、斑块,部分斑块渐出现大小不一的糜烂、溃疡。实验室检查：白蛋白降低,乳酸脱氢酶显著升高。B超示浅表淋巴结肿大、融合,彩色多普勒示淋巴结内部较丰富的树枝样血流信号。CT显示右大腿及会阴部广泛淋巴结肿大伴软组织水肿,上腹部广泛淋巴结肿大,纵膈内淋巴结肿大。皮损组织病理：真皮全层致密分布单一核细胞,部分有异形性及不典型核分裂;免疫组化：CD3、CD8、CD30（阳性细胞占80%）、CD4、CD45RＯ、粒酶B 阳性,CD56、间变性淋巴瘤激酶（ＡＬＫ）、T细胞胞质内抗原1阴性。淋巴结病理：淋巴结结构完全破坏,肿瘤弥漫成片生长,肿瘤细胞比一般的大细胞淋巴瘤瘤细胞大,胞质丰富,嗜碱性或嗜双色性,细胞核偏位,呈马蹄形、肾形或分叶状,核染色质稀疏,可见单个或多个嗜碱性小核仁;免疫组化：CD2、CD4、CD3、粒酶B、上皮膜抗原（EMA）、Ki-67、CD30阳性,CD8、CD56、T细胞胞质内抗原（TIA）-1、ＡＬＫ均为阴性。诊断：间变性淋巴瘤激酶阴性的原发系统型间变性大细胞淋巴瘤泛发性皮肤侵犯。     

Skin involvement as the first symptom of rapidly progressive ALK‐positive systemic anaplastic large cell lymphoma

Systemic anaplastic large cell lymphomas (sALCLs) comprise a heterogeneous group of relatively rare T‐cell non‐Hodgkin lymphomas that are characterized by CD30 expression. Anaplastic lymphoma kinase (ALK)‐positive ALCL is a type of sALCL that commonly involves lymph nodes and extranodal sites. Skin involvement usually presents as tumours, nodules and ulcers. We describe an unusual case of ALK‐positive ALCL in an 11‐year‐old Chinese boy, who initially presented with skin eruption with rapid progression and poor prognosis. This case emphasizes the value of clinical factors to predict the prognosis of ALK‐positive sALCL, and we recommend close collaboration between dermatologists, pathologists and haematologists/oncologists to assure the correct diagnosis and treatment.     

CD30 positive anaplastic large‐cell lymphoma mimicking Langerhans cell histiocytosis

The presence of CD 1a+ dendritic cells (DC) has been well described in T‐cell lymphoproliferative disorders, and the presence of large numbers of DCs has rarely been reported as a mimicker of Langerhans cell histiocytsis (LCH). We present the case of a 56‐year‐old female with a solitary nodule on the chin whose case was referred to our institution for confirmation of the diagnosis of LCH. Skin biopsy showed an ulcerated nodule containing a wedge‐shaped infiltrate comprised of large atypical cells and cells with prominent grooved nuclei. The constellation of histologic and immunologic features favored a CD30 lymphoproliferative disorder of T‐cell lineage even though there were accompanying numerous dendritic histiocytes and CD1a positive Langerhans cells. The sheets of CD30 positive atypical lymphoid cells which express T‐cell markers were consistent with CD30 positive lymphoproliferative disease and favor CD30 positive anaplastic large‐cell lymphoma (ALCL) over Langerhans histiocytosis. The absence of Anaplastic Lymphoma Kinase (ALK) staining favored a primary cutaneous origin. This case signifies a CD 30+ ALCL of the skin which histopathologically mimics a LCH. Ezra N, Van Dyke GS, Binder SW. CD30 positive anaplastic large‐cell lymphoma (ALCL) mimicking Langerhans cell histiocytosis (LCH).     

Pediatric case of anaplastic lymphoma kinase‐positive anaplastic large cell lymphoma forming a solitary skin tumor on the forearm

A 5‐year‐old girl noticed a rapidly growing reddish nodule on her right forearm. Although oral antibiotics had been administrated for 2 weeks, the tumor enlarged. Skin biopsy revealed excessive infiltration of atypical neoplastic cells expressing CD4, CD30 and anaplastic lymphoma kinase (ALK). These histological and immunohistochemical findings were consistent with anaplastic large cell lymphoma (ALCL). Computed tomography showed multiple lymphadenopathy, but lymph node biopsy and bone marrow examination did not show any evidence of systemic dissemination. However, due to the positive results for ALK and multiple lymphadenopathy, we diagnosed ALK‐positive ALCL forming a solitary skin tumor on the forearm. The patient received chemotherapy and presented marked improvement. This paper discusses the difficulty of diagnosing pediatric ALK‐positive ALCL limited to the skin and reviews the medical published work.     

CD30(+) ALK(−) anaplastisch großzelliges primär kutanes T-Zell-Lymphom

Anaplastic large cell lymphomas (ALCL) are characterized by large, pleomorphic cells with a strong expression of cytokine receptor CD 30. We present a 71-year-old patient with several nodules on the right temple extending to his right ear. Based on clinical, histological and immunophenotypic criteria, the diagnosis of a primary cutaneous CD30(+) ALK(?) anaplastic large cell lymphoma was made. After local excision and adjuvant radiotherapy no relapse occurred during a follow-up period of three months.     

A case of anaplastic large cell lymphoma of skeletal muscle

Anaplastic large cell lymphoma (ALCL) is a high grade non‐Hodgkin lymphoma (NHL) that is comprised of the malignant proliferation of large lymphoid cells, which express CD30. Primary ALCL of the skeletal muscle is extremely uncommon. A 51‐year‐old Japanese female presented at our hospital with a 2‐month history of severe pain and swelling of the right leg. A gallium‐67 SPECT/CT scan showed a large mass involving the skeletal muscles from the gluteus to femoris. A biopsy of the mass demonstrated diffuse infiltration of medium and large neoplastic cells with round or lobulated hyperchromatic pleomorphic nuclei. A subset of Reed‐Sternberg‐like cells was also identified. Immunohistochemically, the neoplastic cells were strongly positive for CD4 and CD30, but negative for CD3, CD8, anaplastic lymphoma kinase (ALK), CD20, CD79α, CD21 and CD23. Based on the histological examination, this patient was diagnosed to have ALK‐negative ALCL of the skeletal muscle. Further studies are needed to clarify the biological behavior of primary skeletal muscle ALCL.     

ALK‐positive (2p23 rearranged) anaplastic large cell lymphoma with localization to the skin in a pediatric patient

Anaplastic large cell lymphoma (ALCL) either as primary cutaneous or nodal disease is rare in children and difficult to distinguish, which is important both prognostically and for treatment purposes. We present a case of anaplastic lymphoma kinase (ALK)+ skin‐limited ALCL that highlights this challenge and draws attention to pitfalls in assessing ALK status. The patient was an 11‐year old girl with a twice recurrent nodule on her right shoulder. Each biopsy revealed a deep infiltrate of atypical lymphocytes that expressed CD3, CD4, CD43, CD45RO and CD30. The initial biopsy was epithelial membrane antigen (EMA)+ with vague cytoplasmic ALK‐1 positivity by immunohistochemistry, while the second biopsy was EMA+ and nuclear ALK‐1+. Fluorescence in situ hybridization analysis for an ALK (2p23) rearrangement of the first specimen was negative, while an ALK gene rearrangement was present in the second specimen. Therefore, this case was treated as nodal ALCL, despite negative bone marrow and radiographic imaging studies. The patient was treated with combination chemotherapy and remains disease‐free. Demonstration of nuclear ALK‐positivity, ALK (2p23) gene rearrangement is suggestive of systemic ALCL. Without evidence of systemic disease, this case highlights challenges of skin‐limited ALCL, whose clinical behavior as either cutaneous ALCL systemic ALCL may not be immediately apparent.     

ALK‐positive primary cutaneous T‐cell‐lymphoma (CTCL) with unusual clinical presentation and aggressive course

Anaplastic lymphoma kinase (ALK) expression is uncommon in primary cutaneous T‐cell‐lymphomas (CTCL). We report the case of a patient who was initially diagnosed with small plaque parapsoriasis, and eventually developed an unusual manifestation of CTCL 6 years later. The disease was characterized by aggressively ulcerating plaques and tumors of the entire skin. Histopathology revealed monoclonal proliferation of atypical T‐lymphocytes and CD30‐positive blasts with expression of ALK and identification of an ATIC‐ALK fusion protein. Extensive staging confirmed the primary cutaneous origin of the lymphoma. After failure of several conventional treatments including polychemotherapy, the patient finally achieved remission after receiving brentuximab‐vedotin, alemtuzumab and subsequent allogeneic stem cell transplantation. In the following, the patient developed inflammatory cutaneous lesions that pathologically showed no evidence for lymphoma relapse or classical cutaneous graft‐versus‐host disease. The patient responded to immunosuppression, but finally died from multi‐organ failure due to sepsis 8 months after stem cell transplantation. This is a rare instance of ALK positivity in a CTCL, most likely resembling CD30+ transformed mycosis fungoides, because it was not typical for cutaneous anaplastic large cell lymphoma (ALCL). In contrast to its role in systemic ALCL as favorable prognostic marker, ALK expression here was associated with an aggressive course.     

ALK‐negative systemic intravascular anaplastic large cell lymphoma presenting in the skin

Systemic cases of the CD30‐positive T‐cell neoplasm, anaplastic large cell lymphoma (ALCL), are typically anaplastic lymphoma kinase (ALK)‐positive. The failure to express ALK protein has been shown to portend a worse prognosis. We describe a case of ALK‐negative systemic ALCL that presented as a violaceous plaque on the scalp of a 79‐year‐old man. Interestingly, the neoplastic cells were confined largely within vascular spaces, a configuration that is exceedingly rare in the skin and is more typically seen with intravascular large B‐cell lymphoma. In addition, bcl‐2 immunohistochemical staining was strongly positive in this case, which may portend a more aggressive clinical course. To our knowledge, this report represents the first case of an ALK‐negative ALCL to present intravascularly in the skin. Therefore, the recognition of systemic anaplastic T‐cell lymphoma present within the intravascular spaces is important to avoid misdiagnosis. Rieger K, Polidore T, Warnke R, Kim J. ALK‐negative systemic intravascular anaplastic large cell lymphoma presenting in the skin.     

A case of systemic anaplastic large cell lymphoma with ‘Hodgkin‐like’ appearance and skin involvement mimicking lymphomatoid papulosis

We report a unique case of the CD30+ anaplastic large cell lymphoma (ALCL). A 44‐year‐old Japanese male presented with lymphadenopathy followed by skin involvement. Initially, a swollen cervical lymph node was recognized in 1989 and relapsed in 1991, which was histologically diagnosed as Hodgkin disease of nodular sclerotic type. In 1996, he presented ulcerative cutaneous nodules and swollen lymph nodes in his left inguinal region, which was then diagnosed with CD30+ ALCL. Both the lymphadenopathy and the skin lesion had been completely remitted by combining chemotherapy followed by radiotherapy. Thereafter, he had relapsing and remitting episodes of multiple papules and nodules on his face, trunk and extremities for 10 years. Repeated histopathological examination revealed similar tumor cell proliferation in the papules/nodules of the skin. Essentially similar immunohistochemical features, including CD30 and granzyme B expression, but not anaplastic lymphoma kinase (ALK), strongly suggested that all these tumors were sequential expression of one disease continued for 19 years. This case was finally diagnosed as CD30+ ALCL with unique skin involvement mimicking lymphomatoid papulosis (LyP). Kiniwa Y, Ide Y, Fukushima M, Asano N, Saida T. A case of systemic anaplastic large cell lymphoma with ‘Hodgkin‐like’ appearance and skin involvement mimicking lymphomatoid papulosis.     

累及中枢神经系统的皮肤CD30~+间变性大细胞淋巴瘤1例

患者男,75岁,反复皮肤肿块11年。1个月前第3次复发伴语言、记忆和生活自理能力减退。头颅MRI示:左额叶,右顶叶多发占位,颅内淋巴瘤浸润。左大腿肿块组织病理示:真皮内大量异型细胞,体积较大,形态不规则,核扭曲,核分裂相可见;免疫组化:CD3(+),UCHL-1(+),CD30(+),ALK(-),MIB-1>90%。诊断:皮肤CD30+间变性大细胞淋巴瘤。中枢神经系统(central nerve system,CNS)累及可以是皮肤间变性大细胞淋巴瘤发生皮外累及的唯一部位,患者的意识改变是进行CNS筛查的重要提示。     

Multiple myeloma and cutaneous anaplastic large T‐cell lymphoma in the same patient: Is there a causal relation?

Synchronous occurrence of lymphomatous proliferations of B and T lineage in the same patient is a very rare event and still poorly understood. All the cases reported in the English language literature are described as single case reports. We report a case of 49‐year‐old man, with 2‐year history of multiple myeloma, presented with a raised, erythematous and ulcerated nodule in the anterior aspect of his right thigh. Histologic examination of biopsy specimen showed a dense dermic infiltrate made of large balastic cells displaying anaplastic morphology with no epidermotropism. Immunohistochemical study showed that tumor cells stained positive with CD30, EMA and CD4, and negative for CD3, CD8, CD5, CD20, CD79a, CD138 and anaplastic lymphoma kinase 1 (ALK or Ki‐1). Tangour M, Chelly I, Haouet S, Zitouna M, Kchir N. Multiple myeloma and cutaneous anaplastic large T‐cell lymphoma in the same patient: Is there a causal relation?     

Anaplastic large cell lymphoma: an unusual presentation in a 7-year-old girl

Anaplastic large cell lymphoma (ALCL) accounts for 10% to 30% of all childhood lymphomas and approximately 5% of all non-Hodgkin's lymphoma. ALCL is considered to be a T-cell non-Hodgkin's lymphoma that can be divided into two major groups with distinct genetic, immunophenotypic, and clinical behaviors. The first group consists of a spectrum of CD30+ T-cell lymphoproliferative disorders that include primary cutaneous ALCL (C-ALCL) and lymphomatoid papulosis. The second group is systemic ALCL (S-ALCL), which is further divided into two subgroups: anaplastic lymphoma kinase positive (ALK+) and ALK-negative. Between 30% and 60% of S-ALCL express ALK, which is usually the result of a t(2;5) translocation that correlates with onset in the first three decades of life, male predominance, and good prognosis. Although morphologically similar, ALK- ALCL shows varied clinical behaviors and immunophenotypes; is commonly seen in older age groups, with a peak incidence in the sixth decade of life with no preference as to sex; and has an overall poorer prognosis. We present a case of CD30+, ALK- S-ALCL in a 7-year-old girl.     

Atypical fibrous histiocytoma of the skin with CD30 and p80/ALK1 positivity and ALK gene rearrangement

We report the case of a two patients who presented with a solitary, asymptomatic, angiomatoid nodule on the right thigh. Histopathological finding showed a poorly circumscribed lesion, located in the dermis. The morphological aspect strongly suggested the diagnosis of atypical fibrous histiocytoma (AFH), but surprisingly, the neoplastic cells were diffusely CD30+, with a membrane staining devoid of paranuclear dot. The lesions were tested for p80/ALK1 expression. Surprisingly, we found a diffuse cytoplasmic positivity. Interestingly, using break‐apart fluorescent in situ hybridization (FISH), we evidenced an ALK rearrangement in nearly 50% of the neoplastic cells. The expression of CD30 and ALK1 with ALK gene rearrangement raised the possibility of three diagnoses: a primary cutaneous anaplastic large cell lymphoma (ALCL), a cutaneous inflammatory myofibroblastic tumor (IMT), an AFH of the skin associated with ALK gene rearrangement and CD30 positivity. The three hypotheses were discussed and finally, although p80/ALK1 expression and cytogenetic abnormalities in fibrous histiocytoma (FH) are not yet reported to the best of our knowledge, we favored the diagnosis of AFH.