Atypical Lymphocytic Infiltrate Research Articles

Clinical analysis of 10 cases with subcutaneous panniculitis-like T-cell lymphoma and tissue AURKA expression.

Due to its rarity, subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is often misdiagnosed as benign panniculitis, and there are no standardized treatment guidelines for SPTCL. Aurora kinase A (AURKA) plays a regulatory role in both mitosis and meiosis. Cells treated with an AURKA inhibitor showed severe mitotic delay, which triggered apoptosis. Ten cases of SPTCL were collected in this study, and immunohistochemistry was performed to detect AURKA expression in the skin tissues of these cases. Control groups were set as follows: 1) 10 cases of inflammatory panniculitis; 2) 9 healthy individuals. Fisher's exact test was used to compare the positive rates of AURKA among various groups. An average onset age of 27.3 years was found in 10 SPTCL cases. Clinically, these patients primarily presented with multiple subcutaneous nodules on the trunk and lower extremities, accompanied by intermittent high fever. One case showed lymph node metastasis, while no other distant organ metastasis being observed in any case. Pathologically, there was an infiltration of a large number of atypical lymphocytes within the fat lobules, characterized as a cytotoxic type. AURKA stanning was positive in 6 out of 10 SPTCL cases, while no positive cases were found in the control groups. 1) SPTCL predominantly affects young individuals and can be identified by nodular erythema on the trunk, intermittent high fever, and infiltration of atypical cytotoxic lymphocytes within fat lobules. 2) For early-stage cases without metastasis, monotherapy with glucocorticoids or immunosuppressants such as cyclosporine can be considered. 3) High expression of AURKA in SPTCL tissues suggests that AURKA could be a potential biomarker for disease diagnosis, providing a theoretical basis for further targeted therapy.

Primary Cutaneous Acral CD8-Positive Lymphoproliferative Disorder: A Case Report With Nonacral Presentation.

In this study, we describe a patient of primary cutaneous acral CD8-positive lymphoproliferative disorder located in a nonacral region. A 65-year-old male presented with an ill-defined lesion of rubbery consistency and a maximum diameter of 2.5 cm localized in the right thigh. Histologically, it was composed of a diffuse dermal infiltration of medium-sized atypical lymphocytes that expressed CD3, CD8, and TIA-1. In addition, a characteristic paranuclear positivity with CD68 was observed. During the follow-up, the patient had a recurrence of the disease in the abdomen with a lesion showing similar morphology and phenotype. To our knowledge, < 20 patients of primary cutaneous acral CD8-positive lymphoproliferative disorder with a nonacral presentation have been described in English literature. Although rare, its identification is essential to differentiate it from other T-cell lymphoma that express CD8 and cytotoxic markers, and whose clinical courses are very aggressive.

Primary MALT lymphoma of the breast: pathological and radiological characteristics.

Primary Mucosa-associated lymphoid tissue (MALT) lymphoma is a rare diagnosis in the breast, and clinical diagnosis based on radiological features is often challenging. This study aimed to evaluate the clinicopathological, and radiological characteristics of the patients diagnosed with primary breast MALT lymphoma. This study examined 18 cases of primary MALT lymphoma of the breast diagnosed at a single tertiary center between January 2002 to December 2020. Medical charts, radiological imaging and original pathology slides were reviewed for each case. All cases were female (gender assigned at birth) and presented with a palpable mass or an incidental imaging finding. Imaging presentation ranged from mammographic asymmetries, circumscribed masses, and ultrasound masses lacking suspicious features. Seventeen cases were biopsied under ultrasound; one received a diagnostic excision biopsy. Microscopic examination of the breast specimens demonstrated atypical small lymphocyte infiltration with plasmacytoid differentiation and rare lymphoepithelial lesions. Immunohistochemistry was performed in all cases and established the diagnosis. Most patients were treated with radiotherapy, and only three were treated with chemotherapy. The median follow-up period was 4years and 7.5months, and all patients were alive at the last follow-up. Primary MALT breast lymphomas are usually indolent and non-systemic, and local radiotherapy may effectively alleviate local symptoms. Radiological findings show overlap with benign morphological features, which can delay the diagnosis of this unusual etiology. Although further studies involving a larger cohort could help establish the clinical and radiological characteristics of primary breast MALT lymphomas, pathology remains the primary method of diagnosis. University Health Network Ethics Committee (CAPCR/UHN REB number 19-5844), retrospectively registered.

Atypical Intralymphatic T-Cell Proliferation during DRESS Mimicking Intravascular Lymphoma: Case Report

Drug-induced hypersensitivity syndrome or drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe drug-induced reaction that represents a life-threatening condition. The histopathologic appearance of the skin biopsy is nonspecific but may exceptionally show an atypical intralymphatic lymphocytic infiltrate, and mimic an intravascular lymphoma. Through this article, we will report an exceptional case of a patient presenting with skin lesions pointing to a dress, but whose histological appearance, in the presence of adenopathy during physical examination, can lead, by mistake, to the diagnosis of an intralymphatic lymphoma. We aim to highlight the various diagnostic indices allowing the distinction between these two entities, including the immunohistochemical study, the search for the TcR clonal rearrangement and the anatomo-clinical correlation.

A diagnostically challenging case of Lymphoplasmacytic lymphoma involving the kidney clinically mimicking benign hypertension associated chronic kidney disease

Abstract Introduction/Objective Lymphomas involving the kidneys are under-recognized and often do not present clinically with signs and symptoms raising suspicion for a hematological malignancy. Worsening renal function may necessitate renal biopsy, but often the clinical picture may not warrant a biopsy. We herein present a case of lymphoplasmacytic lymphoma involving the kidney clinically mimicking benign renal vascular disease associated chronic kidney disease. Methods/Case Report Elderly male with past medical history of stage 3 chronic kidney disease presumed to be due to benign hypertension and undergoing treatment for the same presented to his nephrologist for routine follow up. His renal parameters were stable, but his high blood pressure seemed to be difficult to control despite maximum medical intervention. Upon the patient’s request to know exact etiology of his kidney problem, a renal biopsy was performed. Histomorphological evaluation revealed multifocal areas of renal parenchymal infiltration by atypical lymphocytic aggregates with background renal parenchyma showing moderate arteriosclerosis, mild interstitial fibrosis, tubular atrophy and no significant glomerulopathy. Further workup of the lymphoid aggregates led to the finding of a low grade CD5 negative, CD10 negative B-cell lymphoma with plasmacytic differentiation. Molecular testing for final characterization revealed a MYD88 mutation, which along with the immunomorphological findings confirmed the diagnosis of lymphoplasmacytic lymphoma (LPL). The patient was referred to hematology-oncology and was recommended to start chemotherapy due to renal involvement. Results (if a Case Study enter NA) n/a Conclusion In medical renal biopsies, lymphocytic infiltrates in areas of interstitial fibrosis are very common, and an atypical lymphocytic infiltrate can be easily overlooked. Pathologists evaluating these biopsies should have a high degree of suspicion for a hematological malignancy if they encounter atypical lymphocytic infiltrates in the renal parenchyma. Accurate diagnosis is essential, as renal lymphoma whether primary or metastatic, requires initiation of timely systemic chemotherapy.

Spontaneous remission of angioimmunoblastic T-cell lymphoma in a child with ataxia–telangiectasia: a case report

BackgroundAngioimmunoblastic T-cell lymphoma is an uncommon subtype of peripheral T-cell lymphoma in children with fewer than 20 cases reported in literature.Case presentationA 3-year-old Omani boy was diagnosed with ataxia–talengectasia presenting with fever and generalized lymphadenopathy. His biopsy revealed atypical lymphocytic infiltrate consistent with the diagnosis of angioimmunoblastic T-cell lymphoma. Within 3 weeks from the initial presentation and without any neoadjuvant therapy, he showed complete recovery of symptoms with absence of fever and regression of all previously affected lymph nodes. He has remained in remission ever since.ConclusionThis is the first report of spontaneous improvement of angioimmunoblastic T-cell lymphoma in a patient with ataxia–telangiectasia who was 3 years old at presentation. Owing to the paucity of similar cases, this report adds valuable diagnostic, therapeutic, and monitoring data.

BI19 Cutaneous post-transplant lymphoproliferative disorder in an immunosuppressed patient

Abstract Post-transplant lymphoproliferative disorders (PTLDs) are a common form of de novo neoplasia developing in patients with immunosuppression following a transplant. The majority are associated with Epstein–Barr virus (EBV) infection. Cutaneous PTLD manifestations are rare and not well documented in literature. We present a case of systemic PTLD with secondary extensive cutaneous involvement 4 months after allogenic stem cell transplant for JAK2-mutated myelofibrosis. A 68-year-old man was admitted to the haematology department with fevers, diarrhoea, cytopenia, EBV viraemia and a nodular rash behind his ears. Biopsies from colonoscopy confirmed monomorphic PTLD with subsequent extensive ileocalceal lymphadenopathy area detected on computed tomography. Asymptomatic, large, hardened violaceous nodules on the head and neck worsened further. Skin biopsy showed an infiltrate of atypical lymphocytes in the dermis, composed predominantly of large lymphoid cells with visible prominent nucleoli. A limited immunohistochemical panel showed positivity for BCL-2 but not CD20. EBV-encoded RNA in situ hybridization was also positive. Features were compatible with cutaneous involvement by the known monomorphic PTLD. Unfortunately, the patient deteriorated with haemodynamic instability due to sepsis, despite two further infusions of rituximab, and was directed to the palliative team. He died soon after the discontinuation of all treatments. PTLD has a wide spectrum of clinical manifestations. It is classified into three nondestructive types: polymorphic, monomorphic and classic Hodgkin lymphoma type. It can have a poor prognosis so it should always be considered as a diagnosis in transplant patients. Monomorphic PTLDs tend to be more aggressive and rarely respond to immunosuppression reduction. On the contrary, primary cutaneous involvement is rare and seems to have a favourable outcome. Treatment depends on the severity of the disease, and both localized and systemic therapies have been used. Transplant patients should have long-term follow-up to diagnose and promptly treat possible complications.

Mycosis Fungoides: A Diagnostic Challenge

Background: Mycosis fungoides (MF) is the most frequent type of cutaneous T-cell lymphomas (CTCL), a heterogeneous group of non-Hodgkin lymphoma of T-cell origin. CTCLs accounts for about 4% of all non-Hodgkin lymphoma. MF mainly involves the skin but in advanced cases it may involve the lymph, blood and other organs. It mimics other skin disorders like erythema necroticans, leprosy, psoriasis etc which leads to delayed diagnosis and subsequent treatment. Case report: A 61 year old male patient visited the OPD of a tertiary care hospital in Eastern India with multiple reddish elevated lesions for last 6 months which later became dome shaped and then ulcerated. He did not have any fever or itching. He informed that he had been taking Homeopathic medicine previously, but the identity of the said medicine could not be confirmed. Physical examination ruled out the presence of pallor, jaundice, oedema and cyanosis. Pulse and BP were within normal range. Systemic examination was unremarkable except mild hepatomegaly. Cutaneous examination revealed multiple erythematous indurated plaques, papules and nodules over chest, abdomen, back, limbs and face. Few of the plaques present on the trunk and left arm had developed ulcers having a necrotic floors. Cervical, axillary and inguinal lymph nodes were palpable, being firm in consistency and mobile in nature. Hair, nail and mucosal examination revealed normal results. Complete blood count (CBC), peripheral blood smear(PBS), serum urea and creatinine level did not deviate from normal findings. Ultrasonography of whole abdomen showed a mildly enlarged liver. A prominent lymph node in the aortocaval groove could be appreciated on the computed tomography(CT) scan of whole abdomen. CT scan of chest revealed bilateral axillary lymphadenopathy. Erythema necroticans, sarcoidosis and CTCL were considered as the differential diagnoses. Lesional biopsy revealed irregular epidermal hyperplasia, parakeratosis and epidermotropism in the absence of spongiosis.There was infiltration of atypical lymphocytes in the epidermis, forming well developed Pautrier’s micro abscesses. The lymphocytes were tagging the dermo-epidermal junction and within the epidermis showing surrounding halo, convoluted nuclei and variable nuclear pleomorphism. Band like papillary dermal lymphoid infiltrate, dermal lymphoid fibroplasia and nodular lymphoid aggregates could be appreciated in the deep dermis. Immunohistochemical tests were performed and the immunophenotypic profile revealed positivity for CD2, CD3, CD5, CD7, CD 8 and TIA1 and negative for CD4, CD20, CD30, CD56 and granzyme B. Based on clinical presentation, histopathology and Immunohistochemical tests, a final diagnosis of MF was made. The patient was then started on systemic antibiotic therapy, due to increased risk of bacterial super infection of lesions due to skin barrier disruption. He was then referred to Oncology department for further treatment. Conclusion: In this case, the male patient was suffering from mycosis fungoides. In the background of its clinical features being similar to other skin disorders like erythema necroticans, clinicians may face a diagnostic dilemma to correctly diagnose it. Timely diagnosis and treatment improves the prognosis in most cases. Histopathological evaluation still remains the investigation of choice.

Cutaneous Involvement of Angioimmunoblastic T-cell Lymphoma

A 74-year-old man with chronic lymphocytic leukemia and angioimmunoblastic T-cell lymphoma (AITL) of the right lung was undergoing evaluation for initiation of chemotherapy. Bendamustine and rituximab were previously initiated but stopped after one month due to adverse effects. The patient subsequently completed 7 years of ibrutinib therapy, which was halted 3 weeks prior to presentation due to its ineffectiveness and significant hematologic lab abnormalities. Treatment with CHOP (cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, prednisone) was proposed, however the patient had a nodule concerning for cellulitis on the left fifth palmar digit requiring treatment prior to chemotherapy initiation. No improvement was seen after courses of cephalexin and doxycycline. Due to a lack of response to these two antibiotics, dermatology was consulted for further evaluation.&#x0D; On physical exam, there was a 1.3-cm red-violaceous crusted nodule on the palmar aspect of the left fifth digit (Figure 1, panel A). Dermoscopy showed central orange-tan pigmentation with loss of normal acral ridge pattern and surrounding irregular vessels (Figure 1, panel B). The differential diagnosis included Sweet syndrome, drug eruption, infection, and malignancy. A punch biopsy was performed and showed an atypical lymphocytic nodular infiltrate with angioinvasive and angiodestructive features, and immunohistochemical stains suggested AITL. The patient’s clinical stage was changed from stage II to stage IV AITL due to skin involvement, and the patient was started on CHOP treatment.&#x0D; AITL is a peripheral CD4+ follicular T-helper cell-based lymphoma that presents with B symptoms and generally has a poor prognosis after conventional chemotherapies [1]. Though rare, AITL has been reported to present with skin manifestations in up to 50% of cases, which typically present as macular or papular eruptions on the trunk, similar to toxic erythema of chemotherapy, drug eruptions, or viral exanthems [2]. However, there are multiple case reports of AITL mimicking a variety of systemic dermatologic or oncologic entities, including dermatomyositis, systemic lupus erythematosus, vasculitis, and urticaria [3].&#x0D; This case of AITL with cutaneous involvement illustrates an uncommon presentation of this peripheral lymphoma that often has skin manifestations. The presence of skin involvement implies an advanced clinical stage, which confers a poorer prognosis [4]. Due to its variable presentations in the skin, it is often misdiagnosed as a vasculitis or exanthem, particularly when its initial presentation is in the skin without prior diagnosis of internal AITL malignancy [3]. As in this case, most patients are treated for their condition with chemotherapy, starting with anthracycline-based chemotherapy, and often require higher-dose or modified therapy due to the short response duration [4]. Here, we highlight the diagnostic challenge of AITL and the clinical importance of its identification for appropriate staging and treatment of this condition.

Nasal Extranodal Natural Killer/T-cell Lymphoma Imitating Squamous Cell Carcinoma: A Case Report.

Nasal extranodal NK/T-cell lymphoma (NNKTL) is a lethal disease due to poor prognosis with rapid progress. A 56-year-old man complained of left nasal obstruction and blood-stained nasal drip for two months. Incisional biopsies were performed at the outpatient department three times, and the diagnosis of SCC was made. The patient underwent wide excision of the entire lesion via endoscopic sinus surgery with navigation. Final pathologic report revealed NNKTL. Pathological examination of the tumor revealed overlying epithelium presenting as pseudoepitheliomatous hyperplasia (PEH), which mimicked SCC invasion, with infiltration of atypical lymphocytes in the deeper sections. Immunohistochemistry supported the diagnosis of NNKTL. Chemoradiotherapy was administered, and a complete response was achieved at the two-year follow-up. The correct diagnosis of NNKTL is essential for prompt treatment and prevention of superfluous surgery. Although the link between PEH and NNKTL may lead to a misdiagnosis of SCC, multiple large and deep biopsies can prevent this dilemma. A biopsy showing ulceration or necrosis can indicate PEH and imply potential malignancy. Repeated biopsies and complete immunohistochemical studies are important for diagnosing NNKTL.

A Case of Angioimmunoblastic T-cell Lymphoma (AITL)

A 84-year-old female noticed erythema over her whole body for several months and was referred to our department for evaluation of her skin eruption. A physical examination revealed millet-sized erythematous papules and macules all over her body, a high body temperature, and a decreased level of consciousness. A laboratory examination showed an elevated white blood cell count (8200/μl), atypical lymphocytes (3%) and sIL-2R (4030U / ml). Computed Tomography showed systemic lymphadenopathy. A lymph node biopsy taken from the left inguinal lymph node revealed destruction of the lymph nodes, enlargement of the high endothelial venules, and atypical lymphocyte infiltration. Based on the clinical findings and laboratory examination, we diagnosed angioimmunoblastic Tcell lymphoma (AITL). AITL is a relatively rare peripheral T-cell lymphoma with severe systemic symptoms such as fever and lymph node swelling. While approximately half of all cases experience skin symptoms, which are one of the initial symptoms, it is difficult to determine the diagnosis due to the various clinical features or many non-specific rashes. We should keep in mind a differential diagnosis of lymphoma in cases of the presence of persistent eruption, systemic symptoms, and the existence of atypical lymphocytes in peripheral blood.

Successful early diagnosis of monomorphic epitheliotropic intestinal T-cell lymphoma manifesting as chronic diarrhea and hypokalemia using video capsule endoscopy and double-balloon enteroscopy.

Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL), formerly known as enteropathy-associated T-cell lymphoma (EATL) type II, is a rare disease with a poor prognosis that is often diagnosed when patients present with intestinal perforation or obstruction. Our patient, a man in his 60s, had a 5-month history of persistent watery diarrhea. Upper and lower gastrointestinal endoscopy, abdominal computed tomography (CT), and stool culture results were unremarkable. He was admitted to our hospital 8 months later with a weight loss of 20kg, general fatigue, and hypokalemia. Contrast-enhanced CT of the abdomen revealed mild thickening and contrast enhancement of the small intestinal wall. Video capsule endoscopy and double-balloon enteroscopy were performed to reveal a broad ulcer in the jejunum and multiple erosions throughout the small intestine. Examination of the biopsy specimens showed infiltration of atypical lymphocytes with pale cytoplasm in the glandular epithelium. The atypical lymphocytes were positive for CD3, CD8, CD56, granzyme B, and T-cell intracellular antigen-1 by immunostaining. Early diagnosis of MEITL was made, and the patient survived for 21months with continuous chemotherapy. Aggressive examination of the small intestine is effective for the early diagnosis of serious diseases, such as MEITL, in patients with chronic diarrhea of unknown origin.

Nasal-type extranodal NK/T cell lymphoma in association with hemophagocytic syndrome: a case report and literature review*

Abstract We present a rare case of nasal-type CD56-negative NK/T-cell lymphoma. The patient developed hemophagocytic syndrome during diagnosis and treatment. The patient presented to our hospital (Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China) with “nasal congestion for 3 months and scattered erythema, nodules, and ulcers all over the body for 1 month.” We analyzed clinical manifestations, skin histopathology, immunohistochemistry, and in situ hybridization results. Histopathology of the skin revealed a moderate amount of atypical lymphocyte infiltration between the entire dermis and collagen bundles. Immunohistochemistry showed the following: CD30 (+), TIA-1 (+), CD3(2GV6) (+), CD5 part (+), CD8 part (+), CD43 (+), CD56 (-), CD4 (-), CD20 (-), PAX5 (-), PCK (-), P63 (-), P40 (-), EGFR (-), Ki-67 (the hot spot LI is approximately 80%), and in situ hybridization EBER-ROCH (+). The diagnosis made was “NK/T cell lymphoma nasal type”. This type of lymphoma is aggressive, progresses quickly, and has a poor prognosis. Early clinical manifestations are extremely atypical, especially in the absence of rash. Analysis of the skin manifestations of the disease has a positive effect on its early diagnosis, early treatment, and prognosis.

Folliculotropic mycosis fungoides treated with topical corticosteroids: A case report and a review of its trichoscopic features

Sir, Folliculotropic mycosis fungoides (FMF) represents 5% of cutaneous lymphomas. It is a rare variant of mycosis fungoides that differs not only by its clinical and histological presentation but also by its prognosis. It is characterized by an infiltrate of atypical lymphocytes in the perifollicular dermis and hair follicles, with or without mucinosis, while epidermotropism may be completely absent. Dermoscopic and trichoscopic features in FMF are variable and not well defined. Herein, we present a unique case of FMF in a female patient with scalp alopecia, which evolved well under topical treatment. We review its trichoscopic findings. A 64-year-old female presented to our dermatology department with a seven-month history of an alopecic plaque on the scalp. No complaints of itching or burning were made. There was a history of arterial hypertension and dyslipidemia, which has been treated by oral medication. A physical examination revealed an erythematous, non-infiltrated, circumscribed alopecia in the frontal region of the scalp 8 cm in size associated with alopecia of the eyebrows (Fig. 1a and 1b). No other cutaneous lesions were evident. There were no other alopecic or infiltrated plaques, no hyperkeratosis or follicular papules, no acneiform lesions. A histopathological examination of a biopsy specimen revealed an epidermis covered with focally parakeratotic hyperkeratosis. The dermis contained a lymphocytic infiltrate in the follicles and the perifollicular areas. The hair follicles were dissociated by Alcian blue-positive edema. Folliculotropic infiltrate showed positive staining for CD3 and CD4. Some lymphocytes were CD20+ (Fig. 3a – 3c). The clinical, histological, and immunohistochemical appearance was consistent with the diagnosis of folliculotropic MF. Further examination showed no extracutaneous involvement. A full blood count and liver and kidney parameters were found to be in the normal range. A thoraco-abdomino-pelvic CT scan was without abnormality. Referring to the WHO/EORTC classification, the patient’s disease was stage IA. We initiated treatment with a high-potency topical corticosteroid with close monitoring. After two months of treatment, improvement was observed (Fig. 1c). No other cutaneous lesions were evident. There were no other alopecic or infiltrated plaques, no hyperkeratosis or follicular papules, no acneiform lesions. A histopathological examination of a biopsy specimen revealed an epidermis covered with focally parakeratotic hyperkeratosis. The dermis contained a lymphocytic infiltrate in the follicles and the perifollicular areas. The hair follicles were dissociated by Alcian blue-positive edema. Folliculotropic infiltrate showed positive staining for CD3 and CD4. Some lymphocytes were CD20+ (Fig. 3a – 3c). The clinical, histological, and immunohistochemical appearance was consistent with the diagnosis of folliculotropic MF. Further examination showed no extracutaneous involvement. A full blood count and liver and kidney parameters were found to be in the normal range. A thoraco-abdomino-pelvic CT scan was without abnormality. Referring to the WHO/EORTC classification, the patient’s disease was stage IA. We initiated treatment with a high-potency topical corticosteroid with close monitoring. After two months of treatment, improvement was observed (Fig. 1c).

Pityriasis lichenoid-like mycosis fungoides

Sir, Mycosis fungoides is a primary cutaneous T–cell lymphoma, secondary clonal proliferation of mature skin-homing T cells, mostly CD4-positive, with a predilection for involving the epidermis. It is an indolent lymphoma that progresses over several years and represents 50% of primary cutaneous T-cell lymphomas [1]. Its clinical presentation is variable, thus leading to several clinical variants. Herein, we describe a rare variant of mycosis fungoides: pityriasis lichenoid-like mycosis fungoides. A 45-year-old female was referred to our department with a papular rash evolving for the last year without regression. The patient had a history of breast carcinoma in complete remission for two years. A clinical examination revealed erythematous, scaly, non-itchy papules covering the entire body but sparing the face (Figs. 1 and 2). There was no scalp involvement or associated lymphadenopathy. Based on the clinical presentation, the suggested diagnosis was pityriasis lichenoid. A histological examination revealed Pautrier’s microabscesses, atypical lymphocyte infiltration along the basal layer and papillary dermis, and prominent epidermotropism (Fig. 3). There was pilotropism without mucin. Besides, hyperkeratosis with focal parakeratosis and perivascular infiltrate were noted. An immunohistochemical analysis revealed infiltrates of T cells expressing CD3, CD2, CD5, and a predominance of CD4-positive T cells in the epidermis compared to CD8-positive T cells. CD7 and CD30 were, however, negative. These findings were consistent with pityriasis lichenoid-like mycosis fungoides. The patient was classified as a IB stage and received UVB phototherapy with good progress.

ICOS Is Widely Expressed in Cutaneous T-Cell Lymphoma and Its Targeting Promotes Potent Killing of Malignant Cells

Background: Advanced cutaneous T-cell lymphomas (CTCLs) remain an unmet medical need. Brentuximab vedotin (BV), an anti-CD30 antibody-drug conjugate (ADC) linked to monomethyl auristatin E (MMAE), do not deliver significant long-term improvements in patient outcomes. More recently, mogamulizumab and anti-KIR3DL2 provided encouraging results but new targeted therapies are needed. Inducible Co-Stimulator (ICOS), a T-cell costimulatory receptor involved in the development of CTCLs, arouses interest.Methods: We used immunohistochemistry to study ICOS expression in skin biopsies of 23 patients with early-stage mycosis fungoides (MF), 12 with transformed MF (TMF) and 17 with Sézary Syndrome (SS), at diagnosis or in relapse. Skin samples from 12 patients with B-cell lymphomas, 14 with CD30 + lymphoproliferative disease (LPD), 12 with primary cutaneous CD4+ small/medium T-cell lympho-proliferative disorder and 13 with angioimmunoblastic T-cell lymphoma (AITL) were used as controls. ICOS expression by circulating Sézary cells and regulatory T cells (Tregs) in patients with SS was evaluated using flow cytometry and compared to healthy donors (HD) lymphocytes. In 5 patients with SS, we also analyzed concomitant biopsies from involved nodes.Then, we investigated the efficacy of anti-ICOS ADCs generated by coupling murine anti-ICOS 314.8 monoclonal antibodies with MMAE and pyrrolobenzodiazepine (PBD), in comparison to BV. We used ICOS + CTCL cell lines (MyLa, MJ and HUT78), murine xenograft models with MyLa and ICOS + Patient Derived Xenografts (PDXs) from patients with SS and AITL.In order to identify the best anti-ICOS clone that we should develop for a clinical trial, we evaluated the affinity of the antibody on the receptor, the internalization capacity of the antibody using pHAb Reactive Dyes kit (Promega®), and the ability of the antibody to act as an ADC using a secondary conjugate (Mab-ZAP kit, Advanced Targeting Systems®).Results: ICOS was highly expressed by the cutaneous atypical lymphocytic infiltrates in respectively 61%, 75% and 88% of patients with early-stage MF, TMF and SS, such as in all the involved nodes. Double staining experiments which were performed in both skin and lymph node revealed that ICOS expression appears mainly restricted to neoplastic CD4 + T-cells, with rare ICOS +CD8 + T-cells in the tumor micro-environment. ICOS expression by circulating Sézary cells was strong: 69 ± 7.3% versus 38.8 ± 7.1% of non-tumoral CD4 + cells (p<0.009; CI95%: 8.7-51.6); and 31 ± 3.2% of CD4+ cells in HD (p<0.0001; CI95%: 20.3-46.3). Percentages of ICOS + Tregs were significantly higher in patients with SS than in HD.In CTCL cell lines, we observed a significant dose-dependent decrease in cell viability in the presence of anti-ICOS-MMAE (IC50 = 8.2ng/mL) and anti-ICOS-PBD (IC50 = 1.2ng/mL) ADCs. In a mouse xenograft model (MyLa), anti-ICOS-MMAE ADCs provided a longer overall survival (OS) than BV (HR=15.2; CI95%: 3.2-71.1; p<0.0006). Finally, in ICOS + PDXs, anti-ICOS-MMAE ADCs significantly improved OS, and reduced the number of tumor cells in the blood, spleen, and bone marrow. No evidence of ADC toxicity was observed in treated mice.Among 8 different anti-ICOS clones, clone 314.8 had the best affinity on MyLa and MJ cell lines. Clones 53.3, 293.1, 92.17, 88.2 and 279.1 also had good affinity to receptor, whereas clones 145.1 and 121.4 had poor affinity. Using the internalization pHAb reactive dyes kit, we found that clones 314.8, 53.3, 92.17, 88.2 internalized significantly better and faster than the other ones. In order to verify if there is a correlation between internalization capacity and ADC effect, clones 53.3, 92.17 and 145.1 were coupled to MMAE. While anti-ICOS-53.3 and anti-ICOS-92.17 ADCs had similar efficacy to anti-ICOS-314.8 ADCs on MyLa, anti-ICOS 145.1 ADCs resulted in significantly lower cell death. Finally, all clones showed good ability to act as ADCs with Mab-ZAP, excluding clones 279.1, 145.1 and 121.4.Discussion: ICOS is a promising therapeutic target because it is expressed both by tumor T-cells and regulatory T-cells. We report for the first time the strong and frequent expression of ICOS in CTCLs, as well as the preclinical efficacy of anti-ICOS ADCs on CTCL cell line and PDXs. These results could be extended to the spectrum of follicular variant peripheral T-cell lymphomas.Conclusion: Collectively, our findings provide the preliminary basis for a therapeutic trial [Display omitted] DisclosuresLopez: Emergence Therapeutics: Current holder of individual stocks in a privately-held company. Bagot: Takeda: Membership on an entity's Board of Directors or advisory committees. Olive: ImCheck Therapeutics: Current holder of individual stocks in a privately-held company, Membership on an entity's Board of Directors or advisory committees; Emergence Therapeutics: Current holder of individual stocks in a privately-held company, Membership on an entity's Board of Directors or advisory committees; Alderaan Biotechnology: Current holder of individual stocks in a privately-held company, Membership on an entity's Board of Directors or advisory committees.

Tre-P-27 - Cutaneous T-cell lymphoma of mycosis fungoides type with CD30 positive transformation and sweet like neutrophilic dermatosis

<h3>Introduction:</h3> Cutaneous lymphomas are malignancies of T- or B-cell origin, with the majority of cases of approximately 75% being cutaneous T-cell lymphomas (CTCL). The main subtype of CTCL include the most frequent mycosis fungoides (MF), accounting for approximately 60% of CTCL. Mycosis fungoides is most often indolent but patients with advanced disease and especially transformed disease with large atypical, often CD30+ lymphocytes have a poor prognosis. The association of neutrophilic dermatosis (ND) with various hematologic disorders is well documented but uncommon with CTCL. <h3>Case report:</h3> An 80 years old woman was admitted for fulminant MF associated to Sweet-like ND not responding to systemic corticosteroids and methotrexate. Clinical symptoms (fever, painful skin nodules) and laboratory parameters (lymphocytosis and neutrophilia) were compatible with Sweet syndrome. Skin histology demonstrated dense, atypical lymphocytic infiltrate and numerous admixed lymphocytes. However, edema in the upper dermis, which is a histological hallmark of Sweet syndrome, was never present in the skin biopsies. After establishing diagnosis of transformed CD30+ MF with concomitant Sweet-like ND, treatment with Brentuximab was initiated and resulted in initial remission with reduction of mSWAT down to 30% from June 2020 to November 2020. However, after 6 cycles of Brentuximab, the MF progressed with new nodular ulcerated lesions, fierce itching and severe skin tenderness. Further, the disease was complicated by a superinfection and sepsis driven by methicillin resistant staphylococcus aureus, and later on pseudomonas aeruginosa. The MF related Sweet-like ND aggravated, paralleled by an overall decrease in the patient's condition. Chemotherapy was contraindicated in the context of infectious complications and deteriorated general condition. As a therapeutic alternative, we initiated a palliative radiotherapy, however, there was a fulminant disease progression and the patient deceased shortly after. <h3>Conclusion:</h3> The association of MF with ND is rare, underreported and seems to be related to poorer prognosis, resistance to treatment and impaired quality of life.

Isolated Colonic Post-Transplantation Lymphoproliferative Disease

A 61-year-old woman with a diagnosis of left-sided ulcerative colitis presented with recurrence of watery nonbloody diarrhea. She was status post liver transplant 2 years prior for primary sclerosing cholangitis, currently on tacrolimus and mesalamine. Following a negative Clostridium difficile polymerase chain reaction, colonoscopy demonstrated Mayo 1 appearance throughout the colon, with an area of friable and hemorrhagic mucosa in the cecum (Figure A). Random colon biopsies showed mild chronic active colitis, but specific biopsies of the cecal patch identified a monomorphous infiltrate of atypical lymphocytes (Figure B).

Cessation of methotrexate and a small intestinal resection provide a good clinical course for a patient with a jejunum perforation induced by a methotrexate-associated lymphoproliferative disorder: a case report

BackgroundMethotrexate (MTX) is a frequently used drug in the treatment of rheumatoid arthritis (RA), but occurrences of lymphoproliferative disorders (LPD) have been reported in patients undergoing an MTX regimen. Almost half of the patients with methotrexate-associated lymphoproliferative disorders (MTX-LPD) have extranodal lesions; moreover, although extremely rare, digestive tract perforations resulting from the extranodal lesions of MTX-LPD have also been reported.Case presentationWe describe the case of an 81-year-old woman with RA who had been prescribed MTX at 6 mg per week for the past 11 years. She was admitted to our hospital with occasional abdominal pain and was first diagnosed with enteritis. Her abdominal pain did not improve, and a computed tomography scan showed abdominal effusion and free air in the abdominal cavity. She was diagnosed with a digestive tract perforation and underwent emergency surgery. The perforation site was identified in the jejunum, and she underwent small intestinal resection around the perforated region. The pathological findings showed an ulcer in the jejunum and infiltration of large atypical lymphocytes around the perforated region. An immunohistochemical examination revealed the expression of a cluster of differentiation 20 and latent membrane protein 1. Considering the patient’s history of RA treated with MTX, she was diagnosed as having Epstein–Barr virus (EBV)-related MTX-LPD with a histological diagnosis of EBVMCU. MTX was discontinued after the surgery, and her soluble interleukin-2 receptor (sIL-2R) levels had returned to normal 1 year later. She has had a good course for the 2 years since surgery and remains asymptomatic with no recurrence of MTX-LPD, as confirmed by the sIL-2R levels.ConclusionWe experienced a rare case of the jejunum perforation induced by MTX-LPD. Since only a few cases have been reported of a patient with small intestinal perforation induced by MTX-LPD, further research is necessary to evaluate the clinicopathological features of MTX-LPD. The patient had disease remission after surgery and by discontinuing MTX treatment; our case did not require chemotherapy. EBV-positive patients, especially those with a pathological presentation of EBVMCU, could have a higher likelihood of remission, which could have been a factor in the present case.

S2516 Rare Cause of Diarrhea in a Liver Transplant Recipient

INTRODUCTION: We present a case of a 63-year-old male who underwent a liver transplant that was found to have diffuse mantle cell lymphoma (MCL) after work-up for diarrhea. CASE DESCRIPTION/METHODS: A 63-year old orthotopic liver transplant (OLT) patient with a past medical history of Hepatitis C cirrhosis complicated by hepatocellular carcinoma pre-transplant presented to the clinic with progressive non-bloody diarrhea and weight loss of 15 pounds. The patient denied night sweats and fatigue. There were no concerning findings on abdominal exam. Abdominal Magnetic Resonance Imaging was completed 3 months before he visited our clinic for abnormal liver function tests and showed stable prominent mesenteric lymph nodes. Colonoscopy showed mild erythema in the rectum and sigmoid colon up to 30 cm proximal to the anal verge (Figure 1). Biopsies were taken from the duodenum, right colon, and left colon. Histologic sections of colonic mucosa revealed prominent infiltrate of small atypical lymphocytes that have round to irregular nuclei, mature chromatin, and scant to moderate clear cytoplasm (Figure 2). The biopsies were suspicious for lymphoma, which prompted a bone marrow biopsy. Pathology revealed 10% of the marrow was mantle cell; Fluorescence In Situ Hybridization revealed 11 ;14 translocations. The patient was later diagnosed with stage 4 MCL with diffuse gastrointestinal involvement; all biopsies tested positive for MCL. DISCUSSION: Often MCL presents in men in their 60's with lymphadenopathy, blood and bone marrow involvement, and splenomegaly. Our patient’s lack of classic symptoms made the diagnosis of MCL quite challenging. To our knowledge, MCL is a rare cause of diarrhea in a post-OLT patient. It is plausible that his atypical presentation may be related to partial masking of symptoms related to immunosuppression. Post-transplant patients are at an increased risk for Hodgkin's Lymphoma in the setting of immunosuppression. However, an increased risk of MCL has not been shown as a complication of immunosuppression. The challenge in this patient is balancing his chemotherapeutic and anti-rejection medications. Cyclosporine was continued with the addition of Ibrutinib. While Ibrutinib has shown promising results in patients with MCL, there have been cases reporting hepatotoxic reactions. Thus far, our patient has not had any drug-induced liver injury from Ibrutinib. In conclusion, it is important to maintain MCL along with a broad differential when working up diarrhea in post-transplant patients.Figure 1Figure 2