case_images: PMC8459905_01
case_images: Lymphomatoid papulosis at disease onset (A-D) and at 8 weeks from the initiation of venetoclax monotherapy (E-H). Intensely pruritic red flat-topped papules with diffuse erythema spreading on >90% body surface area (B, C), accompanied with sparse nodules (A, black arrow, and D). At 8 weeks from the initiation of the potent selective BCL2 inhibitor venetoclax (400 mg daily), a complete response was achieved, as defined by no detectable active skin lesions (E-H), and it is still present (in May 2021), lasting more than 12 months.
case_images: fonc-11-729106-g001.jpg
case_images: PMC8459905_01_fonc-11-729106-g001.jpg
case_images: f1
case_images: In January 2019, CLL progressed with notable lymphocytosis (331,000 x 109/L) and macrocytic anemia [Hb 11.2 g/dl, mean corpuscular volume (MCV) 112 fl], accompanied with supra-/subdiaphragmatic lymphadenopathies (>3 regions) and splenomegaly (longitudinal spleen diameter of 22 cm); no TP53 mutations/deletion underlaid disease progression. Chemoimmunotherapy with intravenous bendamustine (90 mg/m2, days 1 and 2) and rituximab (375 mg/m2, day 1) was then administered (for 6 cycles, every 28 days, from January to July 2019), achieving a partial response. In August 2019, the patient presented with a skin rash of intensely pruritic dusky nodules (n > 10) and red flat-topped papules (n > 300) with erythema involving >90% of body surface area (Figures 1A-D). Very surprisingly, LyP-associated skin lesions completely resolved (zero lesions) along with intractable pruritus within 8 weeks from venetoclax initiation (Figures 1E-H).
case_images: Immunohistochemical analysis of mixed-infiltrate type A lymphomatoid papulosis (LyP). The punch biopsy from the left arm identified a diffuse infiltration of small lymphocytes and few large-sized Hodgkin-like cells that were prevalent in the dermis and subcutis, while largely sparing the epidermis (A, original magnification, x10). Hodgkin-like cells stained positive for CD30 (B, original magnification, x10; and B, inset, original magnification, x40) and were interspersed in a dense lymphoid infiltrate mostly contributed by CD3+ T cells (C, original magnification, x10). The expression of the anti-apoptotic protein BCL2 was strong and pervasive in the LyP tissue (D, original magnification, x10), and it was readily recognized in the reactive lymphoid meshwork and large-sized Hodgkin-like cells (D, inset, black arrow, original magnification, x40).
case_images: fonc-11-729106-g002.jpg
case_images: PMC8459905_01_fonc-11-729106-g002.jpg
case_images: f2
case_images: The punch biopsy specimen obtained from the left arm and stained with hematoxylin and eosin demonstrated an abnormal mixed-lymphoid infiltrate (composed of small lymphocytes and few large-sized Hodgkin-like cells) in the dermis and subcutis, with moderate extension into epidermis (Figure 2A). Immunohistochemical analysis showed that pathological Hodgkin-like cells were CD3+, CD4+, CD30+ (Figure 2B) and CD8-, and were intermingled with numerous inflammatory cells (mostly of T-cell origin; Figure 2C); no monomorphic small neoplastic B cells nor immunoglobulin gene rearrangements were detected in the skin biopsy, thus excluding a diagnosis of B-cell leukemia cutis while proving that the CD30+ cutaneous lymphoproliferative disorder was clonally unrelated to the mature B-cell neoplasm in our case.