- Email: [email protected]
Durable remission of a patient with primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma
Hematol Oncol Stem Cell Ther (2018) xxx, xxx– xxx
Available at www.sciencedirect.com
ScienceDirect journal homepage: www.elsevier.com/locate/hemonc
CASE REPORT
Durable remission of a patient with primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma Shaima M. Al Aoun a, Shahid Iqbal b, Tahani M. AlHalouli c, Syed Z. Zaidi b Ibraheem H. Motabi b,* a
Department of Medicine, Asseer Central Hospital, Abha, Saudi Arabia Department of Adult Hematology/Bone Marrow Transplant, King Fahd Medical City, Riyadh, Saudi Arabia c Department of Pathology, King Fahd Medical City, Riyadh, Saudi Arabia b
Received 1 April 2018; received in revised form 23 July 2018; accepted 6 September 2018
KEYWORDS CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma; Hyper-CVAD; Lymphoma; Multiagent chemotherapy; World Health Organization
Abstract Primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma (CD8+ PCAETL) is a rare disease characterized by aggressive clinical course and short survival. All available data are extracted from case reports and case series. The outcome is dismal and only two reported cases were cured after several lines of therapies including stem cell transplant. We herein present the case of a patient with CD8+ PCAETL who presented with rapidly progressive skin lesions and systemic symptoms. He was treated with aggressive multiagent chemotherapy comprising cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with high-dose methotrexate and cytarabine (hyper-CVAD). The treatment resulted in durable complete remission with no evidence of disease recurrence after 58 months of follow-up. This is the first reported case of durable remission after first-line treatment. Ó 2018 King Faisal Specialist Hospital & Research Centre. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-ncnd/4.0/).
Introduction * Correspondence to: Ibraheem Motabi, MD, Consultant and Chairman, Adult Hematology and BMT, Comprehensive Cancer Center, King Fahad Medical City, Riyadh 11525, Saudi Arabia. E-mail address: [email protected] (I.H. Motabi).
Primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma (CD8+ PCAETL) is a distinct and rare subtype that accounts for less than 1% of all cutaneous Tcell lymphomas. It is associated with a poor outcome with
https://doi.org/10.1016/j.hemonc.2018.09.004 1658-3876/Ó 2018 King Faisal Specialist Hospital & Research Centre. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Please cite this article in press as: Al Aoun SM et al., Durable remission of a patient with primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma ..., Hematol Oncol Stem Cell Ther (2018), https://doi.org/10.1016/j.hemonc.2018.09.004
2
S.M. Al Aoun et al.
a median survival of less than 2 years [1]. It is considered as a provisional entity in the 2016 World Health Organization (WHO) classification of lymphoid neoplasms [2]. This kind of tumor presents with aggressive clinical course and rapidly progressive skin lesions [3,4]. It might be localized or disseminated, manifesting as eruptive papules, nodules, tumors with central ulceration, or necrosis, or may present with superficial, hyperkeratotic patches and plaques. Systemic involvement including the lungs, testes, or central nervous system is frequent at presentation; however, lymph node involvement is uncommon. Treatment has been unsuccessful in the vast majority of reported cases with low rate of complete remission, and relapse after initial treatment is almost universal [5–7]. Here we present a rare case of a patient with CD8+ PCAETL who was successfully treated with a multiagent aggressive chemotherapy protocol that had not been previously published.
Case report A 27-year-old previously healthy male presented to us in October 2013 with high-grade fever, fatigue, 10-kg weight loss, and generalized skin rash for 6 weeks. There was no history of prodromal skin symptoms or lesions in the past. The fever was associated with rigors and chills and was relieved by antipyretics. There were occasional episodes of diarrhea and vomiting. On examination, at presentation, his temperature was 38 °C, blood pressure 107/59 mmHg, heart rate 102 bpm, and oxygen saturation 98% on room air. There were multiple patches and plaques of different sizes involving trunk and limbs with scaly erythematous margins. Some lesions showed areas of central necrosis. Skin lesions were photographed with patient’s consent (Fig. 1). There were also numerous palpable nontender subcutaneous nodules of different sizes. Face and acral areas were spared. Rest of the examination was unremarkable. Complete blood count showed the following: white blood count, 2.2 109 (3.9–11 109/L); hemoglobin, 12.1 g/dL (11– 16 g/dL); platelet count, 182 109/L (155–435 109/L); and erythrocyte sedimentation rate, 11 mm/h. Blood film confirmed leukopenia and it was unremarkable otherwise. Coagulation profile was normal. Biochemistry revealed the following measurements: lactate dehydrogenase, 696 U/L
(125–220 U/L); uric acid, 283 mmol/L (150–350 mmol/L); total bilirubin, 16.5 mmol/L (3–20 mmol/L); direct bilirubin, 7.1 mmol/L (0–8.6 mmol/L); aspartate aminotransferase, 60 U/L (5–34 U/L); alanine aminotransferase, 40 U/L (0–55 U/L); and albumin, 36 g/L (35–50 g/L). Serological tests were negative for hepatitis B virus, hepatitis C virus, hepatitis A virus, human immunodeficiency virus (HIV), human T-cell leukemia-lymphoma virus (HTLV) 1 and 2, and cytomegalovirus (CMV) IgM. Serology for CMV IgG was positive. Skin biopsy specimen was taken from a representative skin lesion and it comprised a CD8-positive superficial dermal lichenoid infiltrate of mostly small- to medium-sized lymphocytes that exhibited prominent epidermotropism. The tumor cells appeared to be larger in size in deeper dermis where the infiltrate was mainly perivascular in distribution. The tumor cells were CD3- and CD8positive T cells (Fig. 2) along with expression of CD5 and CD2, and markedly diminished staining for CD7. There was aberrant expression of both T-cell receptor beta-Fl (BF1) and T-cell receptor c/d. The tumor cells were negative for CD4, CD7, CD20, and CD30. Ki-67 was positive in 60% of tumor cells. Fluorescence in situ hybridization showed no evidence of ALK gene rearrangement. Computerized tomography of the head, neck, chest, and abdomen showed cervical lymphadenopathy, mild cardiomegaly with pericardial effusion, and hepatomegaly with multiple focal lesions. Fludeoxyglucose-positron emission tomography (PET) scan for the whole body showed innumerable hypermetabolic foci involving cutaneous and subcutaneous tissues, muscle, lung, liver, spleen, and spine consistent with lymphoma (Fig. 3). The patient received a total of four cycles of hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (hyper-CVAD) alternating with high-dose methotrexate and cytarabine (completed in March 2014). The therapy was complicated by several episodes of febrile neutropenia, however, with negative cultures, which were treated successfully with broad-spectrum antibiotics. The skin lesions completely disappeared after two cycles of chemotherapy. Follow-up imaging with PET scan after two cycles of chemotherapy showed complete metabolic remission. Follow-up PET scan at the end of therapy indicated complete metabolic remission. The patient was doing well
Fig. 1 Photographs of skin lesions (A and B) demonstrating multiple patches and plaques of different sizes involving limbs with scaly erythematous margins. Some lesions showed areas of central necrosis.
Please cite this article in press as: Al Aoun SM et al., Durable remission of a patient with primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma ..., Hematol Oncol Stem Cell Ther (2018), https://doi.org/10.1016/j.hemonc.2018.09.004
Remission of a patient with PCAETL
3
Fig. 2 Composite skin biopsy images: (A–D) show photomicrographs of skin biopsy (H&E stained) at various magnifications; (A) reflects low power (4?) showing superficial dermal lichenoid infiltration and involvement of deeper dermal layer of the skin; (B–D) at progressively higher magnification sections show superficial dermal lichenoid infiltrate of mostly small- to medium-sized lymphocytes that exhibit prominent epidermotropism. The tumor cells tend to be larger in size in deeper dermis where the infiltrate is mainly perivascular in distribution. Selected immunohistochemistry images demonstrating CD3 and CD8 positivity of the lymphoid infiltrate (E and F).
in complete remission on his last follow-up visit in March 2018.
Discussion CD8+ PCAETL is a rare subtype of cutaneous T-cell lymphoma that has fatal clinical course even with treatment. The diagnosis is sometimes challenging, and it can be difficult to differentiate from other types of cutaneous T-cell lymphoma. Clinical correlation is very useful to discriminate between the indolent type of CD8+ cutaneous T-cell lymphoma and CD8+ PCAETL as both may have similar pathological findings. Primary cutaneous c/d T-cell lymphoma (PCGDTL) presents with similar clinical course and should be considered in the differential diagnosis. The tumor cells in CD8+ PCAETL are typically positive for BF1 (ab T-cell receptor) and negative for the cd T-cell receptor. In our
case, BF1 was positive with an aberrant expression of the cd T-cell receptor. Variable T-cell receptor heterodimer expression patterns have been described with BF1+/cd being the most common phenotype [1]. A subset of cases is either double positive or double negative for T-cell receptors. The phenotype BF1–/cd+ and CD8 negativity is typical for PCGDTL. There are no available clinical trials to guide the treatment of this disease. Case reports and case series are the only available source of information on treatment outcome. It has been treated with different kinds of protocols mostly used for cutaneous T-cell not otherwise specified. Several patients have received variable therapies with disappointing outcome. These include CHOP (cyclophosphamide, doxorubicin [hydroxydaunomycin], vincristine [Oncovin], prednisolone), methotrexate, interferon-a, or photochemotherapy (psoralen plus ultraviolet A [PUVA]). The response to these protocols was dismal. In addition,
Please cite this article in press as: Al Aoun SM et al., Durable remission of a patient with primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma ..., Hematol Oncol Stem Cell Ther (2018), https://doi.org/10.1016/j.hemonc.2018.09.004
4
S.M. Al Aoun et al. of patients with CD8+ PCAETL is reported to be very poor with median survival of less than 2 years. So far, we found only two cases in the literature who could survive with this disease [9,10]. One of them had relapsed after autologous SCT and later received allogenic SCT (allo-SCT). The other received intensive chemotherapy followed by allo-SCT and then brentuximab for post-transplant relapse. To the best of our knowledge, this is the first case reported that has attained complete remission after first line of therapy and did not require any salvage therapy or consolidation with SCT and has survived for more than 4 years. The patient tolerated the therapy very well and at 58 months of follow-up, he is alive without disease. In our case, we found PET scan immensely helpful for staging and for evaluation of treatment response. Considering the rarity of disease, randomized trials are not possible. We suggest that aggressive chemotherapy protocol similar to ours may be used as first-line therapy. However, our findings need to be evaluated by other investigators.
Conclusion Aggressive chemotherapy regimen like hyper-CVAD as a first-line therapy might be curative in this subtype of Tcell lymphoma. However, our findings need to be evaluated by other investigators.
Conflicts of interest The authors have no conflicts of interest to declare.
References
Fig. 3 Fludeoxyglucose positron emission tomography scan for the whole body. (A) Maximum intensity projection (MIP) scout image before therapy showing innumerable hypermetabolic foci of lymphoma involving cutaneous and subcutaneous tissues, muscle, lung, liver, spleen, and spine. (B) MIP scout image after four cycles of chemotherapy demonstrating total resolution of hypermetabolic foci.
patients either failed to achieve remission or had short-lived responses with invariable relapse. The treatment of relapse was not less than a challenge as it required multiple subsequent therapies (gemcitabine and oxaliplatin, brentuximab, romidepsin, DHAP (Dexamethasone, high dose cytarabine, and cisplatin), donor lymphocyte infusion, cyclophosphamide, and stem cell transplant [SCT]) [8]. The survival
[1] Guitart J, Martinez-Escala ME, Subtil A, Duvic M, Pulitzer MP, Olsen EA, et al. Primary cutaneous aggressive epidermotropic cytotoxic T-cell lymphomas: reappraisal of a provisional entity in the 2016 WHO classification of cutaneous lymphomas. Mod Pathol 2017;30:761–72. [2] Swerdlow SH, Campo E, Pileri SA, Harris NL, Stein H, Siebert R, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood 2016;127: 2375–90. [3] Berti E, Tomasini D, Vermeer MH, Meijer CJ, Alessi E, Willemze R. Primary cutaneous CD8-positive epidermotropic cytotoxic T cell lymphomas. A distinct clinicopathological entity with an aggressive clinical behavior. Am J Pathol 1999;155:483–92. [4] Robson A, Assaf C, Bagot M, Burg G, Calonje E, Castillo C, et al. Aggressive epidermotropic cutaneous CD8+ lymphoma: a cutaneous lymphoma with distinct clinical and pathological features. Report of an EORTC cutaneous lymphoma task force workshop. Histopathology 2015;67:425–41. [5] Csomor J, Bogna ´r A, Benedek S, Sinko ´ J, Fekete S, Krena ´cs L, et al. Rare provisional entity: primary cutaneous aggressive epidermotropic CD8+ cytotoxic T-cell lymphoma in a young woman. J Clin Pathol 2008;61:770–2. [6] Du-Thanh A, Durand L, Costes V, Guillot B, Dereure O. Aggressive T cytotoxic CD8+ epidermotropic cutaneous lymphoma: a case in a patient with Steinert’s myotonic dystrophy. Ann Dermatol Venereol 2006;133:991–4 [Article in French]. [7] Intriago BM, Pen ˜a OC, Gray HA, Cabrera CM, Martı´nez CV. Primary cutaneous aggressive epidermotropic cytotoxic CD8 positive T cell lymphoma: report of one case. Rev Med Chil 2012;140:368–72 [Article in Spanish].
Please cite this article in press as: Al Aoun SM et al., Durable remission of a patient with primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma ..., Hematol Oncol Stem Cell Ther (2018), https://doi.org/10.1016/j.hemonc.2018.09.004
Remission of a patient with PCAETL [8] Cyrenne BM, Gibson JF, Subtil A, Girardi M, Isufi I, Seropian S, et al. Transplantation in the treatment of primary cutaneous aggressive epidermotropic cytotoxic CD8-positive T-cell lymphoma. Clin Lymphoma Myeloma Leuk 2018;18:e85–93. [9] Cyrenne BM, Subtil A, Girardi M, Foss F. Primary cutaneous aggressive epidermotropic cytotoxic CD8+ T-cell lymphoma:
5 long-term remission after brentuximab vedotin. Int J Dermatol 2017;56:1448–50. [10] Liu V, Cutler CS, Young AZ. Case 38–2007. N Engl J Med 2007;357:2496–505.
Please cite this article in press as: Al Aoun SM et al., Durable remission of a patient with primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma ..., Hematol Oncol Stem Cell Ther (2018), https://doi.org/10.1016/j.hemonc.2018.09.004
Available at www.sciencedirect.com
ScienceDirect journal homepage: www.elsevier.com/locate/hemonc
CASE REPORT
Durable remission of a patient with primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma Shaima M. Al Aoun a, Shahid Iqbal b, Tahani M. AlHalouli c, Syed Z. Zaidi b Ibraheem H. Motabi b,* a
Department of Medicine, Asseer Central Hospital, Abha, Saudi Arabia Department of Adult Hematology/Bone Marrow Transplant, King Fahd Medical City, Riyadh, Saudi Arabia c Department of Pathology, King Fahd Medical City, Riyadh, Saudi Arabia b
Received 1 April 2018; received in revised form 23 July 2018; accepted 6 September 2018
KEYWORDS CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma; Hyper-CVAD; Lymphoma; Multiagent chemotherapy; World Health Organization
Abstract Primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma (CD8+ PCAETL) is a rare disease characterized by aggressive clinical course and short survival. All available data are extracted from case reports and case series. The outcome is dismal and only two reported cases were cured after several lines of therapies including stem cell transplant. We herein present the case of a patient with CD8+ PCAETL who presented with rapidly progressive skin lesions and systemic symptoms. He was treated with aggressive multiagent chemotherapy comprising cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with high-dose methotrexate and cytarabine (hyper-CVAD). The treatment resulted in durable complete remission with no evidence of disease recurrence after 58 months of follow-up. This is the first reported case of durable remission after first-line treatment. Ó 2018 King Faisal Specialist Hospital & Research Centre. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-ncnd/4.0/).
Introduction * Correspondence to: Ibraheem Motabi, MD, Consultant and Chairman, Adult Hematology and BMT, Comprehensive Cancer Center, King Fahad Medical City, Riyadh 11525, Saudi Arabia. E-mail address: [email protected] (I.H. Motabi).
Primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma (CD8+ PCAETL) is a distinct and rare subtype that accounts for less than 1% of all cutaneous Tcell lymphomas. It is associated with a poor outcome with
https://doi.org/10.1016/j.hemonc.2018.09.004 1658-3876/Ó 2018 King Faisal Specialist Hospital & Research Centre. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Please cite this article in press as: Al Aoun SM et al., Durable remission of a patient with primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma ..., Hematol Oncol Stem Cell Ther (2018), https://doi.org/10.1016/j.hemonc.2018.09.004
2
S.M. Al Aoun et al.
a median survival of less than 2 years [1]. It is considered as a provisional entity in the 2016 World Health Organization (WHO) classification of lymphoid neoplasms [2]. This kind of tumor presents with aggressive clinical course and rapidly progressive skin lesions [3,4]. It might be localized or disseminated, manifesting as eruptive papules, nodules, tumors with central ulceration, or necrosis, or may present with superficial, hyperkeratotic patches and plaques. Systemic involvement including the lungs, testes, or central nervous system is frequent at presentation; however, lymph node involvement is uncommon. Treatment has been unsuccessful in the vast majority of reported cases with low rate of complete remission, and relapse after initial treatment is almost universal [5–7]. Here we present a rare case of a patient with CD8+ PCAETL who was successfully treated with a multiagent aggressive chemotherapy protocol that had not been previously published.
Case report A 27-year-old previously healthy male presented to us in October 2013 with high-grade fever, fatigue, 10-kg weight loss, and generalized skin rash for 6 weeks. There was no history of prodromal skin symptoms or lesions in the past. The fever was associated with rigors and chills and was relieved by antipyretics. There were occasional episodes of diarrhea and vomiting. On examination, at presentation, his temperature was 38 °C, blood pressure 107/59 mmHg, heart rate 102 bpm, and oxygen saturation 98% on room air. There were multiple patches and plaques of different sizes involving trunk and limbs with scaly erythematous margins. Some lesions showed areas of central necrosis. Skin lesions were photographed with patient’s consent (Fig. 1). There were also numerous palpable nontender subcutaneous nodules of different sizes. Face and acral areas were spared. Rest of the examination was unremarkable. Complete blood count showed the following: white blood count, 2.2 109 (3.9–11 109/L); hemoglobin, 12.1 g/dL (11– 16 g/dL); platelet count, 182 109/L (155–435 109/L); and erythrocyte sedimentation rate, 11 mm/h. Blood film confirmed leukopenia and it was unremarkable otherwise. Coagulation profile was normal. Biochemistry revealed the following measurements: lactate dehydrogenase, 696 U/L
(125–220 U/L); uric acid, 283 mmol/L (150–350 mmol/L); total bilirubin, 16.5 mmol/L (3–20 mmol/L); direct bilirubin, 7.1 mmol/L (0–8.6 mmol/L); aspartate aminotransferase, 60 U/L (5–34 U/L); alanine aminotransferase, 40 U/L (0–55 U/L); and albumin, 36 g/L (35–50 g/L). Serological tests were negative for hepatitis B virus, hepatitis C virus, hepatitis A virus, human immunodeficiency virus (HIV), human T-cell leukemia-lymphoma virus (HTLV) 1 and 2, and cytomegalovirus (CMV) IgM. Serology for CMV IgG was positive. Skin biopsy specimen was taken from a representative skin lesion and it comprised a CD8-positive superficial dermal lichenoid infiltrate of mostly small- to medium-sized lymphocytes that exhibited prominent epidermotropism. The tumor cells appeared to be larger in size in deeper dermis where the infiltrate was mainly perivascular in distribution. The tumor cells were CD3- and CD8positive T cells (Fig. 2) along with expression of CD5 and CD2, and markedly diminished staining for CD7. There was aberrant expression of both T-cell receptor beta-Fl (BF1) and T-cell receptor c/d. The tumor cells were negative for CD4, CD7, CD20, and CD30. Ki-67 was positive in 60% of tumor cells. Fluorescence in situ hybridization showed no evidence of ALK gene rearrangement. Computerized tomography of the head, neck, chest, and abdomen showed cervical lymphadenopathy, mild cardiomegaly with pericardial effusion, and hepatomegaly with multiple focal lesions. Fludeoxyglucose-positron emission tomography (PET) scan for the whole body showed innumerable hypermetabolic foci involving cutaneous and subcutaneous tissues, muscle, lung, liver, spleen, and spine consistent with lymphoma (Fig. 3). The patient received a total of four cycles of hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (hyper-CVAD) alternating with high-dose methotrexate and cytarabine (completed in March 2014). The therapy was complicated by several episodes of febrile neutropenia, however, with negative cultures, which were treated successfully with broad-spectrum antibiotics. The skin lesions completely disappeared after two cycles of chemotherapy. Follow-up imaging with PET scan after two cycles of chemotherapy showed complete metabolic remission. Follow-up PET scan at the end of therapy indicated complete metabolic remission. The patient was doing well
Fig. 1 Photographs of skin lesions (A and B) demonstrating multiple patches and plaques of different sizes involving limbs with scaly erythematous margins. Some lesions showed areas of central necrosis.
Please cite this article in press as: Al Aoun SM et al., Durable remission of a patient with primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma ..., Hematol Oncol Stem Cell Ther (2018), https://doi.org/10.1016/j.hemonc.2018.09.004
Remission of a patient with PCAETL
3
Fig. 2 Composite skin biopsy images: (A–D) show photomicrographs of skin biopsy (H&E stained) at various magnifications; (A) reflects low power (4?) showing superficial dermal lichenoid infiltration and involvement of deeper dermal layer of the skin; (B–D) at progressively higher magnification sections show superficial dermal lichenoid infiltrate of mostly small- to medium-sized lymphocytes that exhibit prominent epidermotropism. The tumor cells tend to be larger in size in deeper dermis where the infiltrate is mainly perivascular in distribution. Selected immunohistochemistry images demonstrating CD3 and CD8 positivity of the lymphoid infiltrate (E and F).
in complete remission on his last follow-up visit in March 2018.
Discussion CD8+ PCAETL is a rare subtype of cutaneous T-cell lymphoma that has fatal clinical course even with treatment. The diagnosis is sometimes challenging, and it can be difficult to differentiate from other types of cutaneous T-cell lymphoma. Clinical correlation is very useful to discriminate between the indolent type of CD8+ cutaneous T-cell lymphoma and CD8+ PCAETL as both may have similar pathological findings. Primary cutaneous c/d T-cell lymphoma (PCGDTL) presents with similar clinical course and should be considered in the differential diagnosis. The tumor cells in CD8+ PCAETL are typically positive for BF1 (ab T-cell receptor) and negative for the cd T-cell receptor. In our
case, BF1 was positive with an aberrant expression of the cd T-cell receptor. Variable T-cell receptor heterodimer expression patterns have been described with BF1+/cd being the most common phenotype [1]. A subset of cases is either double positive or double negative for T-cell receptors. The phenotype BF1–/cd+ and CD8 negativity is typical for PCGDTL. There are no available clinical trials to guide the treatment of this disease. Case reports and case series are the only available source of information on treatment outcome. It has been treated with different kinds of protocols mostly used for cutaneous T-cell not otherwise specified. Several patients have received variable therapies with disappointing outcome. These include CHOP (cyclophosphamide, doxorubicin [hydroxydaunomycin], vincristine [Oncovin], prednisolone), methotrexate, interferon-a, or photochemotherapy (psoralen plus ultraviolet A [PUVA]). The response to these protocols was dismal. In addition,
Please cite this article in press as: Al Aoun SM et al., Durable remission of a patient with primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma ..., Hematol Oncol Stem Cell Ther (2018), https://doi.org/10.1016/j.hemonc.2018.09.004
4
S.M. Al Aoun et al. of patients with CD8+ PCAETL is reported to be very poor with median survival of less than 2 years. So far, we found only two cases in the literature who could survive with this disease [9,10]. One of them had relapsed after autologous SCT and later received allogenic SCT (allo-SCT). The other received intensive chemotherapy followed by allo-SCT and then brentuximab for post-transplant relapse. To the best of our knowledge, this is the first case reported that has attained complete remission after first line of therapy and did not require any salvage therapy or consolidation with SCT and has survived for more than 4 years. The patient tolerated the therapy very well and at 58 months of follow-up, he is alive without disease. In our case, we found PET scan immensely helpful for staging and for evaluation of treatment response. Considering the rarity of disease, randomized trials are not possible. We suggest that aggressive chemotherapy protocol similar to ours may be used as first-line therapy. However, our findings need to be evaluated by other investigators.
Conclusion Aggressive chemotherapy regimen like hyper-CVAD as a first-line therapy might be curative in this subtype of Tcell lymphoma. However, our findings need to be evaluated by other investigators.
Conflicts of interest The authors have no conflicts of interest to declare.
References
Fig. 3 Fludeoxyglucose positron emission tomography scan for the whole body. (A) Maximum intensity projection (MIP) scout image before therapy showing innumerable hypermetabolic foci of lymphoma involving cutaneous and subcutaneous tissues, muscle, lung, liver, spleen, and spine. (B) MIP scout image after four cycles of chemotherapy demonstrating total resolution of hypermetabolic foci.
patients either failed to achieve remission or had short-lived responses with invariable relapse. The treatment of relapse was not less than a challenge as it required multiple subsequent therapies (gemcitabine and oxaliplatin, brentuximab, romidepsin, DHAP (Dexamethasone, high dose cytarabine, and cisplatin), donor lymphocyte infusion, cyclophosphamide, and stem cell transplant [SCT]) [8]. The survival
[1] Guitart J, Martinez-Escala ME, Subtil A, Duvic M, Pulitzer MP, Olsen EA, et al. Primary cutaneous aggressive epidermotropic cytotoxic T-cell lymphomas: reappraisal of a provisional entity in the 2016 WHO classification of cutaneous lymphomas. Mod Pathol 2017;30:761–72. [2] Swerdlow SH, Campo E, Pileri SA, Harris NL, Stein H, Siebert R, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood 2016;127: 2375–90. [3] Berti E, Tomasini D, Vermeer MH, Meijer CJ, Alessi E, Willemze R. Primary cutaneous CD8-positive epidermotropic cytotoxic T cell lymphomas. A distinct clinicopathological entity with an aggressive clinical behavior. Am J Pathol 1999;155:483–92. [4] Robson A, Assaf C, Bagot M, Burg G, Calonje E, Castillo C, et al. Aggressive epidermotropic cutaneous CD8+ lymphoma: a cutaneous lymphoma with distinct clinical and pathological features. Report of an EORTC cutaneous lymphoma task force workshop. Histopathology 2015;67:425–41. [5] Csomor J, Bogna ´r A, Benedek S, Sinko ´ J, Fekete S, Krena ´cs L, et al. Rare provisional entity: primary cutaneous aggressive epidermotropic CD8+ cytotoxic T-cell lymphoma in a young woman. J Clin Pathol 2008;61:770–2. [6] Du-Thanh A, Durand L, Costes V, Guillot B, Dereure O. Aggressive T cytotoxic CD8+ epidermotropic cutaneous lymphoma: a case in a patient with Steinert’s myotonic dystrophy. Ann Dermatol Venereol 2006;133:991–4 [Article in French]. [7] Intriago BM, Pen ˜a OC, Gray HA, Cabrera CM, Martı´nez CV. Primary cutaneous aggressive epidermotropic cytotoxic CD8 positive T cell lymphoma: report of one case. Rev Med Chil 2012;140:368–72 [Article in Spanish].
Please cite this article in press as: Al Aoun SM et al., Durable remission of a patient with primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma ..., Hematol Oncol Stem Cell Ther (2018), https://doi.org/10.1016/j.hemonc.2018.09.004
Remission of a patient with PCAETL [8] Cyrenne BM, Gibson JF, Subtil A, Girardi M, Isufi I, Seropian S, et al. Transplantation in the treatment of primary cutaneous aggressive epidermotropic cytotoxic CD8-positive T-cell lymphoma. Clin Lymphoma Myeloma Leuk 2018;18:e85–93. [9] Cyrenne BM, Subtil A, Girardi M, Foss F. Primary cutaneous aggressive epidermotropic cytotoxic CD8+ T-cell lymphoma:
5 long-term remission after brentuximab vedotin. Int J Dermatol 2017;56:1448–50. [10] Liu V, Cutler CS, Young AZ. Case 38–2007. N Engl J Med 2007;357:2496–505.
Please cite this article in press as: Al Aoun SM et al., Durable remission of a patient with primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma ..., Hematol Oncol Stem Cell Ther (2018), https://doi.org/10.1016/j.hemonc.2018.09.004