Breast implant-associated ALK-negative anaplastic large cell lymphoma: a case report and discussion of possible pathogenesis

Breast implant associated anaplastic large cell lymphoma (BIA-ALCL) is a recently recognized clinical entity, with only 39 well-documented cases reported worldwide, including 3 fatalities. Because of its rarity, the clinical and pathologic features of this malignancy have yet to be fully defined. Moreover, the pathogenesis of ALCL in association with textured silicone gel breast implants is poorly understood. Here we report a case of BIA-ALCL arising in a 67-year-old woman with a mastectomy due to breast cancer followed by implantation of textured silicone gel breast prosthesis. The patient presented with breast enlargement and tenderness 8 years following reconstructive surgery. MRI revealed a fluid collection surrounding the affected breast implant. Pathologic examination confirmed the presence of malignant ALCL T cells that were CD30+, CD8+, CD15+, HLA-DR+, CD25+ ALK- and p53. A diagnosis of indolent BIA-ALCL was made since tumor cells were not found outside of the capsule. Interestingly, an extensive mixed lymphocytic infiltrate and ectopic lymphoid tissue (lymphoid neogenesis) adjacent to the fibrous implant capsule were present. The patient was treated with capsulectomy and implantation of new breast prostheses. Six months later, the patient was found to have BIA-ALCL involvement of an axillary lymph node with cytogenetic evolutionof the tumor. To our knowledge, this is the sixth reported case of aggressive BIA-ALCL. Unique features of this case include the association with lymphoid neogenesis and the in vivo cytogenetic progression of the tumor. This case provides insight into the potential role of chronic inflammation and genetic instability in the pathogenesis of BIA-ALCL.     

Breast implant-associated anaplastic large-cell lymphoma: A series of two case reports diagnosed by cytopathology

Breast implant-associated anaplastic large-cell lymphoma (BIA-ALCL) is a rare T-cell lymphoma with a good prognosis. It occurs in association with textured breast implants. Its most common presentation is a late-onset peri-implant effusion. We present two cases of BIA-ALCL diagnosed by cytopathological examination of the fluid collection and describe the cytopathologic findings. Both patients were disease free after implant removal. This report highlights the contribution of the cytopathologic analysis to early diagnosis and definite treatment of BIA-ALCL.     

A case of breast implant-associated anaplastic large cell lymphoma (BIA-ALCL)

Breast implant associated anaplastic large cell lymphoma (BIA-ALCL) is a recognized but rare complication of breast implantation. This condition occurs with textured implants and on average, presents around 10 years post insertion. We report a case of BIA-ALCL and describe the histological and cytological examination findings. Furthermore, we discuss the condition in more detail, how this disease may be staged and the requirement for central registration.     

Cytological features of breast implant‐associated anaplastic large cell lymphoma in pleural effusion

Breast implant‐associated anaplastic large cell lymphoma (BIA‐ALCL) is a very rare CD30‐positive ALK‐negative T‐cell non‐Hodgkin lymphoma included as a provisional entity in the 2017 WHO classification of lymphoid neoplasms. BIA‐ALCL arises as proliferating cells over the surface of the implant. It is generally an indolent disease if confined within the fibrous capsule. In contrast, mass and/or infiltration beyond the capsule is much more aggressive. This report describes a case of infiltrative BIA‐ALCL with massive pleural effusion containing hallmark BIA‐ALCL cells showing the characteristic morphologic appearance of high‐grade anaplastic lymphoma, CD30‐positive but ALK‐negative with variable staining for T‐cell antigens. Detailed cytological features of BIA‐ALCL in pleural fluid are described along with the results of a literature search performed for BIA‐ALCL cases with pleural effusion. This report expands the spectrum of BIA‐ALCL pathology to include chest wall involvement and pleural effusion.     

A case of anaplastic lymphoma kinase‐positive large B‐cell lymphoma: Aspiration cytology findings

Anaplastic lymphoma kinase‐positive (ALK+) large B‐cell lymphoma (LBCL) is a rare subtype of non‐Hodgkin B‐cell lymphoma that exhibits a more aggressive clinical course and poorer prognosis than the typical diffuse large B‐cell lymphoma. In this study, we report the case of a 67‐year‐old man with left cervical lymph node swelling. Aspiration cytology revealed many clusters of cohesive, large, and solitary cells. The tumor cells had abundant cytoplasm and large round‐to‐oval nuclei with prominent nucleoli. The Giemsa staining specimens exhibited amorphous global bodies adjacent to some clusters. Histologically, large tumor cells occupied the lymph nodes in a sinusoidal pattern, and immunohistochemically, these cells were cytokeratin?, CD19^?, CD20^?, CD79a^?, CD3^?, CD30^?, CD138⁺, IgG^?, IgA⁺, and ALK⁺. Chromogenic in situ hybridization revealed restricted immunoglobulin light‐chain expression. Fluorescent in situ hybridization demonstrated translocation of the ALK gene. The tumor cells were negative for Epstein–Barr virus and human herpesvirus 8. It is important to differentiate ALK+LBCL from metastatic carcinoma and other lymphoma subtypes with similar histological features to ensure a proper treatment strategy and prediction of prognosis. Diagn. Cytopathol. 2014;42:69–72. © 2013 Wiley Periodicals, Inc.     

Anaplastic large-cell non-Hodgkin’s lymphoma of the breast in periprosthetic localisation 32 years after treatment for primary breast cancer—a case report

Primary, as well as secondary, lymphomas of the breast are rare diseases and might, in some cases, be misdiagnosed as breast cancer on routine hematoxylin/eosin stainings. We report a case of an anaplastic large cell lymphoma in a 72-year-old woman with a history of breast cancer treated with breast-ablative surgery and a subsequent silicon implant 32 years ago. Clinically, she presented with an ulceration of the skin, which had developed within a few months. On conventional histology, the tumor cells were mimicking poorly differentiated invasive ductal carcinoma with a prominent leukocytic infiltrate. The immunoprofile of the tumor showed negativity for cytokeratins and led to the diagnosis of a CD30-positive anaplastic large cell lymphoma.     

Is ALK‐gene rearrangement overlooked in primary gastrointestinal T‐cell lymphomas? About two cases

A 41‐year‐old male patient with a history of ankylosing spondylitis and Crohn disease, treated with immunomodulators and disease‐modifying drugs, was diagnosed with a primary intestinal T‐cell lymphoma that followed a 7.5‐year‐course. This transmural proliferation lacked cytological characteristics of anaplastic large cell lymphoma (ALCL), and was CD8‐positive, and CD30‐ and anaplastic lymphoma kinase (ALK)‐negative by immunohistochemistry (IHC). However, ALK‐gene rearrangement (ALK‐gr) was detected by fluorescence in situ hybridization (FISH) in both initial and persistent disease. The possibility of indolent T‐cell lymphoproliferative disease of the gastrointestinal tract with atypical features (transmural involvement) related to ALK‐gr was suggested. A previous case of aggressive ‘enteropathy‐associated ALCL’ in the context of celiac disease was recently reported, which also lacked anaplastic morphology, and where CD30 and ALK expression was incidentally demonstrated by IHC, and ALK‐gr subsequently confirmed by FISH. These two recent cases represent two distinct rare entities pertaining to the group of primary intestinal T‐cell lymphomas, and they both show unexpected ALK‐gr. This suggests that ALK‐gr has been overlooked in the group of primary intestinal T‐cell lymphomas. Performing IHC and FISH tests for ALK‐gr in primary gastrointestinal T‐cell lymphomas might be of importance, particularly with the advancement of targeted therapy that could impact treatment and prognosis.     

Cytopathologic findings and differential diagnostic considerations of primary clear cell carcinoma of the lung

Primary clear cell carcinoma (CLCC) of the lung is an extremely rare disease and is a subtype of large cell carcinoma, according to the World Health Organization (WHO) classification. A case is presented here in which intraoperative squash smears in a 53‐year‐old man revealed sheet and small clusters or tumor cells with prominent nucleoli and fine granular chromatin. Abundant translucent cytoplasm with occasional cytoplasmic vacuoles and intracytoplasmic eosinophilic inclusions was also identified. A cytopathologic diagnosis of a CLCC was suggested. Further evaluation and immunohistochemical studies were conducted on formalin‐fixed, paraffin‐embedded material. Nests of slightly acidophilic clear tumor cells with a prominent cellular membrane and an alveolar growth pattern were identified on H&E sections. Immunohistochemically, the tumor cells showed diffuse and strong membranous staining for CK(AE1/AE3), CK7, and CA19‐9 but were negative for Napsin A, CK20, CDX2, TTF‐1, alpha‐fetoprotein, chromogranin A, synaptophysin, CD10, and CD56. The diagnosis of primary CLCC of the lung was confirmed based on cytopathologic, histopathologic, immunohistochemical results, and a detailed systemic examination to exclude a possible extrapulmonary origin. We report here the cytopathological features of CLCC of the lung with an emphasis on differential diagnostic considerations. Diagn. Cytopathol. 2013. © 2011 Wiley Periodicals, Inc.     

Primary Hodgkin lymphoma of the stomach--a case report

A case of a 69-year-old male with a one-month history or recurrent attacks of GI bleeding, secondary anemic syndrome and epigastric pain is reported. Endoscopic examination revealed a tumorous lesion suspicious of malignancy. Neither lymphadenopathy nor any other tumorous lesion was identified by extensive clinical examination. In the biopsy specimens there was ulcerated gastric mucosa with an infiltration by lymphoid cells, predominantly of mature T-cell type. Atypical large cells with large nuclei with prominent nucleoli were dispersed among the mature lymphocytes. These atypical cells were both mono- and binucleated (Hodgkin and RS cells). Both cell types revealed immunohistochemically membranous and dot-like perinuclear positivity of CD30 and CD15 antigens. Based on morphologic features and immunohistochemical findings, a diagnosis of primary gastric Hodgkin lymphoma was established. Diagnostic approach, as well as differential diagnosis of primary Hodgkin lymphoma in this extremely rare location, are discussed.     

Acute myeloid leukemia with myelodysplasia-related changes with erythroid differentiation involving pleural fluid: a case report and brief cytopathologic review

The vast majority of malignant pleural effusions are caused by metastatic adenocarcinoma, most frequently from breast or lung primaries. However, a minority of cases show evidence of involvement by a hematopoietic neoplasm such as lymphoma or leukemia. We report a rare case of a 54-year-old male with a prior diagnosis of acute myeloid leukemia with myelodysplastic-related changes (AML-MDS) with erythroid differentiation having new onset pleural effusions containing leukemic blasts. The pleural specimen was comprised of blast forms having large round nuclei with finely dispersed chromatin and prominent nucleoli, with scattered binucleate forms. The blasts expressed CD45 and CD34 and were negative for epithelial and mesothelial markers. Previous bone marrow biopsies had shown that the blasts exhibited strong staining for hemoglobin and lacked expression of Factor VIII and myeloperoxidase, consistent with erythroid differentiation. Although rare, this case indicates the need for consideration of unusual disease states presenting within a pleural fluid and highlights the differential diagnosis and immunohistochemical profile of AMLs with erythroid differentiation.     

Nucleolated variant of mantle cell lymphoma with leukemic manifestations mimicking prolymphocytic leukemia

Chronic lymphoproliferative disorders sometimes can be difficult to classify. We report 4 cases characterized by large cells with distinct central nucleoli, reminiscent of prolymphocytic leukemia, but shown on further workup to represent mantle cell lymphoma. At initial examination, the patients had generalized lymphadenopathy, splenomegaly, and a leukemic blood picture. The peripheral blood showed many large cells with round to slightly irregular nuclei, single central nucleoli, and a fair amount of pale cytoplasm. The picture was not typical of prolymphocytic leukemia because of the presence of generalized lymphadenopathy and the large size of the circulating abnormal cells. Immunophenotypic study showed that the large lymphoid cells were CD5+ CD23- mature B cells with overexpression of cyclin D1, and cytogenetic study demonstrated the translocation t(11;14)(q13;q32) in 3 patients. Lymph node biopsy confirmed a diagnosis of mantle cell lymphoma, pleomorphic variant, in all 4 patients. This study documents the existence of an unusual leukemic form of mantle cell lymphoma with prominent nucleoli; the clinicopathologic features that distinguish it from other chronic lymphoproliferative disorders are discussed.     

A Case of Adult T-cell Leukemia/Lymphoma, Histologically Presenting CD30-Positive Large Cell Lymphoma

A 48 year old Japanese woman with adult T-cell leuke-mia/lymphoma (ATLL), histologically presenting CD30 positive large cell lymphoma is reported. The patient, who was from an ATLL endemic area in Japan, had cutaneous nodules in the head, trunk, and extremities, and cervical lymph node swelling; these had been found three months before her admission to our hospital. A biopsy specimen of a skin lesion showed diffuse large cell lymphoma; the lymphoma cells were positively stained with CD30 (Ki 1/ Ber H 2), CD4 (helper T), and CD25 (interleukin 2 receptor) antibodies. Anti HTLV-1 antibody (ATLA) was detected in the serum, and molecular cytogenetic studies of lymphoma cells showed both positive T-cell receptor rearrangement and HTLV-1 specific DNA sequences.     

Pulmonary non‐Hodgkin's lymphoma (NHL) of diffuse large B‐cell type with simultaneous humeral involvement in a young lady: An uncommon presentation with cytologic implications

A bronchogenic carcinoma, almost invariably, presents as a lung mass. Primary pulmonary lymphomas are rare. We report an unusual case of a pulmonary non‐Hodgkin's lymphoma (NHL) with simultaneous involvement of the right humerus in a 37 year old lady. Bronchial lavage smears showed atypical cells with irregular nuclear membranes raising a suspicion of a hematolymphoid tumor, over a small cell carcinoma that was the closest differential diagnosis. Biopsy from the lung mass and from the lesion in the humerus showed an identical malignant round cell tumor with prominent apoptosis. On immunohistochemistry (IHC), tumor cells were diffusely positive for leukocyte common antigen (LCA), CD20 and MIB1 (70%), while negative for cytokeratin (CK), epithelial membrane antigen (EMA) synaptophysin, chromogranin, neuron specific enolase (NSE), CD3, and CD10. Diagnosis of a pulmonary NHL of diffuse large B‐cell type with involvement of the humerus was formed. The case is presented to create an index of suspicion for the possibility of a NHL on respiratory samples, while dealing with small round cells with irregular nuclear membranes. IHC is necessary to confirm he diagnosis. A simultaneous association in the humerus in our case makes it unusual. Diagn. Cytopathol. 2010. © 2009 Wiley‐Liss, Inc.     

CK阳性T细胞淋巴瘤1例报道并文献复习

目的 研究CK呈阳性表达的非霍奇金小T细胞性淋巴瘤的病理学特征及鉴别诊断。方法 运用光镜、电镜及免疫组化技术，观察1例CK呈阳性表达非霍奇金小T细胞性淋巴瘤的组织学、超微结构形态及免疫组化特征并复习相关文献。结果 肿瘤组织主由弥漫分布的小圆形细胞构成。核仁不明显。CD45、CD45RO、和CK(广谱、低分子量、高分子量和19、)均为( )。CD20和CD79均为(-)。电镜观察瘤细胞胞核圆形，居中。胞质少．可见线粒体．未见上皮细胞分化特征、神经内分泌颗粒。结论 非霍奇金小T细胞性淋巴瘤偶可呈CK阳性表达，在应用免疫组化技术对低分化肿瘤进行鉴别诊断时应注意肿瘤组织的异常表达。     

Fine-needle aspiration cytology: true histiocytic lymphoma/histiocytic sarcoma

True histiocytic lymphoma/histiocytic sarcoma is an extremely rare, malignant histiocytic tumor. This report is of such a case in a 52-yr-old woman. Fine-needle aspiration (FNA) smears showed large pleomorphic nuclei, prominent nucleoli, moderately dense abundant cytoplasm, and scattered cells with cytoplasmic vacuoles and some with reniform nuclei. Small numbers of background lymphocytes and benign histiocytes were present as well as many multinucleated tumor cells. The immunophenotype was CD45, Lysozyme, CD68 (PGMI), CD43, and S-100 positive. Genotypic analysis revealed a germline configuration. This type of tumor has a large cytological differential diagnosis and immunophenotyping is essential for diagnosis.     

Cytomorphology and immunohistochemistry of extrarenal rhabdoid tumor: a case report with review of literature

Extrarenal rhabdoid tumor (ERRT) is a rare, aggressive tumor with extremely poor prognosis. We report a case of ERRT with intraspinal extension in a 1.5-year-old child diagnosed by fine needle aspiration cytology (FNAC) and immunohistochemistry. The child presented with a right lumbar region lump of two months duration. Ultrasound guided FNAC was performed and cell block was prepared. Smears were highly cellular and showed a dispersed population of large round cells having abundant pale eosinophilic cytoplasm, centrally to eccentrically placed nucleus with large prominent nucleoli. Immunohistochemistry was carried out on cell block which was positive for epithelial membrane antigen EMA and Vimentin. It was negative for leucocyte common antigen [LCA], wilms tumor 1, WT1, desmin and neuron specific enolase NSE, thus ruling out other tumors like lymphoma, Wilms tumor, rhabdomyosarcoma, and neuroblastoma. A final diagnosis of ERRT was given. ERRT is an extremely rare tumor of retroperitoneal area; it should be included in the differential diagnosis of malignant round cell tumor in children. Cell block in this case is mandatory for putting up the panel of immunohistochemistry which can clinch the diagnosis of rhabdoid tumor and treatment can be started as early as possible.     

Adrenal extranodal NK/T‐cell lymphoma diagnosed by fine‐needle aspiration and cerebrospinal fluid cytology and immunophenotyping: A case report

The cytologic findings of an extranodal NK/T‐cell lymphoma (NKTCL) presenting as a large adrenal mass with leptomeningeal involvement diagnosed by CT‐guided fine‐needle aspiration and cerebrospinal fluid (CSF) cytology are described. The 65‐year‐old Caucasian patient presented with progressive headache and multiple cranial nerve neuropathies. Magnetic resonance imaging showed leptomeningeal enhancement surrounding the conus medullaris and cauda equine, and a subsequent PET/CT demonstrated a large right adrenal gland mass. Fine‐needle aspiration of the adrenal mass showed occasional large pleomorphic cells with prominent nucleoli, moderate amounts of cytoplasm, and rare large cells with sparse cytoplasmic granules admixed with numerous small lymphocytes. Initial flow cytometry from this sample showed no clonal B‐cell population. Immunoperoxidase stains performed on the cell block/core specimen showed that the large atypical cells were positive for CD2, CD30, CD43 and CD56, TIA‐1, granzyme, and perforin, but for none of the other T‐cell markers used (CD3, CD4, CD5, CD8, CD45RO), which stained the abundant background lymphocytes. A CSF specimen showed similar neoplastic cells and flow cytometry showed an NK‐cell population with aberrant immunophenotype. The cytologic findings of the neoplastic cells and the extensive panel of immunoperoxidase stains allowed the diagnosis of NKTCL, which was confirmed by the subsequent flow‐cytometric immunophenotyping performed on the CSF. This is, to the best of our knowledge, the first case of NKTCL diagnosed by FNA of the adrenal gland and by CSF cytology. Diagn. Cytopathol. 2009. © 2009 Wiley‐Liss, Inc.     

Anaplastic large‐cell lymphoma associated with breast implants: A unique entity within the spectrum of peri‐implant effusions

Anaplastic large‐cell lymphoma (ALCL) is a rare and newly described complication associated with breast implants. Patients often present with a peri‐implant effusion, which is amenable to fine‐needle aspiration. The laboratory handling of peri‐implant effusions for cytology and ancillary studies is as crucial as recognizing the characteristic cytology of ALCL. All cases of peri‐implant effusions were retrieved from the PathWest database between January 2003 and May 2013, yielding four cases of breast implant‐associated ALCL and six benign samples. The cytological features were evaluated and information from ancillary studies collated. Clinical and follow‐up histology was available in all cases. All ALCL cases contained highly atypical lymphoid cells including ‘hallmark' cells. In contrast, benign peri‐implant effusions showed a mixture of inflammatory cells, being either neutrophil‐rich (three cases) or lymphocyte‐rich (three cases). A CD30 positive, ALK1 negative immunophenotype was demonstrated in all cases on cell block immunohistochemistry. Flow cytometry and T‐cell receptor clonality studies confirmed aberrant T‐cell immunophenotype in four of four and clonally rearranged T‐cell receptor antigens in three of three cases. ALCL was identified in three of four subsequent capsulectomies. Staging confirmed disease limited to the capsular tissue or peri‐implant effusion in all cases. None of the six patients with benign peri‐implant effusions developed lymphoma during follow‐up. Cases of ALCL accounted for 40% of peri‐implant effusions received over a 10‐year period, indicating the rarity of these samples and the high likelihood of malignancy. Awareness of this entity and its presentation should allow for appropriate triage of these specimens and definitive diagnosis on effusion specimens. Diagn. Cytopathol. 2014;42:929–938. © 2014 Wiley Periodicals, Inc.     

B cell lymphoma,unclassifiable, with features intermediate between diffuse large B cell lymphoma and classical hodgkin lymphoma: Diagnosis by fine‐needle aspiration cytology

A 58‐year‐old lady presented with mediastinal lymphadenopathy. A thoracoscopic ultrasound‐guided fine‐needle aspiration showed large atypical epithelioid cells arranged in cohesive sheets and dispersed as single cells with intact cytoplasm amid a background of lymphocytes and histiocytes. A cytological diagnosis of “a malignant neoplasm” was made, raising a broad list of differential diagnoses. A broad panel of immunocytochemical stains performed on the cell block was indicative of a lymphoproliferative disorder, but the immunophenotype was intermediate between diffuse large B cell lymphoma (DLBCL) and classical Hodgkin lymphoma (cHL). Diffuse and strong reactivity to CD20, CD79a, and PAX‐5, and weak reactivity to CD30, was in favor of a DLBCL, or more precisely mediastinal (thymic) large B cell lymphoma (MLBL). However, there were negative staining for LCA, OCT‐2, and BOB‐1 as well as positive staining for EBV‐encoded RNA, which were against a diagnosis of MLBL and raised the possibility of cHL. The absence of RS cells and the typical mileu, the negativity for CD15 and the strong positivity of CD20 and PAX‐5 were against a diagnosis of cHL. On this basis, the diagnosis of “B‐cell lymphoproliferative disorder with features intermediate between DLBCL and cHL” was rendered. The diagnosis was subsequently confirmed on excisional biopsy. This case report demonstrates broad differential diagnoses raised by this diagnostic entity and the importance of an adequate cell block for accurate designation. Diagn. Cytopathol. 2014;42:690–693. © 2013 Wiley Periodicals, Inc.