Case Report
A 72-year-old woman with a persistent cough and abnormal chest X-ray T-cell lymphomas are a form of lymphoproliferative disease broadly categorized as being either primary cutaneous or peripheral. There is considerable overlap in their clinical presentation, but confirming the precise disease subtype is critical since it has implications for prognosis and treatment strategy. Its rarity means guidelines for treatment are limited, with more aggressive approaches usually reserved for high risk or refractory cases. This article reports the case of a woman previously treated for presumed primary cutaneous T-cell lymphoma who developed isolated pulmonary recurrence at a 3-year interval – a rare finding in this condition and indicative of this actually being a form of peripheral T-cell lymphoma all along.
Discussion
T-cell lymphomas are a heterogeneous group of lymphoproliferative conditions. In broad terms, they are classified as primary cutaneous T-cell lymphomas or peripheral T-cell lymphomas. However, peripheral T-cell lymphoma can involve the skin and even present as isolated skin lesions, so there is considerable overlap. It is increasingly recognized that subtypes of cutaneous T-cell lymphoma and peripheral T-cell lymphoma are very different Dr John P Corcoran is Specialist Registrar in Respiratory Medicine, Dr Alastair J Moore is Consultant Respiratory Physician and Dr Ling-Pei Ho is Consultant Respiratory Physician in the Oxford Centre for Respiratory Medicine, Oxford University Hospitals NHS Trust, Churchill Hospital, Oxford OX3 7LE, Dr Susan J Davies is Consultant Pathologist in the Department of Cellular Pathology and Dr Graham P Collins is Consultant Haematologist in the Department of Clinical Haematology, Oxford University Hospitals NHS Trust, Oxford Correspondence to: Dr JP Corcoran ([email protected])
652
with respect to their clinical behaviour and response to treatment (Willemze et al, 2005). This has led to a separation of
those that display more benign behaviour, such as lymphomatoid papulosis and cutaneous anaplastic large cell lym-
Figure 1. a. Axial and (b) coronal computed tomography images demonstrating bilateral parenchymal and endobronchial nodularity with larger left lower and right middle lobe soft tissue masses.
a
b
Case Report
A 72-year-old woman was seen in clinic with a 3-month history of persistent dry cough and chest X-ray arranged by her GP that had demonstrated bilateral pulmonary nodules. The patient’s medical history was notable only for a skin cancer – labelled as a primary cutaneous T-cell lymphoma – diagnosed 3 years previously and successfully treated with excision biopsy and radiotherapy. Other than a persistent cough she described no concerning features including haemoptysis, weight loss, anorexia, dyspnoea or chest pain. She was a lifelong non-smoker with no occupational risk factors for lung disease. On examination the patient was afebrile with normal resting oxygen saturations. Cardiovascular and abdominal examinations were unremarkable; pulmonary examination revealed fine inspiratory crackles at the left base only. Routine bloods including full blood count, clotting screen, renal function, liver function and serum calcium were within normal limits. Computed tomography scan of the thorax (Figure 1) demonstrated a 5 cm soft tissue mass narrowing the left main bronchus with further smaller nodules visualized within the large airways and lung parenchyma bilaterally. Subsequent whole body positron emission tomography scan confirmed that pathological fludeoxyglucose uptake was confined to the thorax only. Flexible bronchoscopy identified multiple pink gelatinous lesions throughout the bronchial tree (Figure 2a) with the largest masses narrowing the left main and right middle lobe bronchi. Biopsies (Figures 2b and c) revealed infiltration of the bronchial mucosa with neoplastic cells strongly expressing CD30 and CD2, scattered staining for CD4 and negative for other markers including CD56, synaptophisin, cytokeratin, CD20 and ALK-1. MIB-1 proliferative index was greater than 80%. These immunohistochemistry results prompted comparison with the skin biopsy histology from 3 years previously, demonstrating morphological similarities and allowing confirmation of the diagnosis of recurrent peripheral T-cell lymphoma with isolated pulmonary disease. The patient underwent treatment with combination chemotherapy (six cycles of CHOP – cyclophosphamide, doxorubicin, vincristine and prednisolone) to complete remission and 1 year later remained systemically disease-free on interval positron emission tomography-computed tomography. She intermittently develops transient migratory skin lesions (consistent with a pattern of lymphomatoid papulosis) that have been biopsied and confirmed as CD30-positive peripheral T-cell lymphoma, and remains under long-term haematology outpatient follow up.
© 2014 MA Healthcare Ltd
Introduction
British Journal of Hospital Medicine, November 2014, Vol 75, No 11
h Journal of Hospital Medicine. Downloaded from magonlinelibrary.com by 139.080.123.051 on December 12, 2015. For personal use only. No other uses without permission. . All rights rese
Case Report involvement, associated with a worse prognosis. Treatment usually involves combination chemotherapy; more aggressive approaches such as autologous haemopoietic stem cell transplantation and radiation therapy are controversial and generally used in patients whose disease is either refractory or considered high risk on the basis of subtype and prognostic index (Sonnen et al, 2005). BJHM
a
c
b
Figure 2. a. Bronchoscopic view of distinct soft-tissue lesions in the mid-trachea. b and c. Haematoxylin and eosin stain of endobronchial biopsies showing infiltration of atypical lymphoid cells at (b) x10 and (c) x20 power.
phoma, from clinically aggressive forms including HTLV-1 positive adult T-cell lymphoma where the median survival is less than 6 months. Peripheral T-cell lymphoma is a rare condition which accounts for 10% of cases of non-Hodgkin lymphoma. This fact, in combination with the heterogeneity of the disease, has presented a significant challenge in developing guidelines. Collaborative work through the International peripheral T-cell lymphoma Project has compensated by combining data from multiple sources to inform the evidence base for both prognostic and therapeutic purposes (Foss et al, 2011), although individualized treatment strategies for patients remain some way off
(Moskowitz et al, 2012). Pulmonary and particularly endobronchial disease in the context of peripheral T-cell lymphoma is unusual and, as with other types of visceral
Foss FM, Zinzani PL, Vose JM et al (2011) Peripheral T-cell lymphoma. Blood 117(25): 6756–67 (doi: 10.1182/blood-2010-05-231548) Moskowitz AJ, Lunning MA, Horwitz SM (2012) Should patients with aggressive peripheral T-cell lymphoma all be treated the same?: no… well yes, …but maybe not for long. Cancer J 18(5): 445–9 (doi: 10.1097/PPO.0b013e31826aeeb2) Sonnen R, Schmidt WP, Muller-Hermelink HK, Schmitz N (2005) The International Prognostic Index determines the outcome of patients with nodal mature T-cell lymphomas. Br J Haematol 129(3): 366–72 (doi: 10.1111/j.1365-2141.2005.05478.x) Willemze R, Jaffe ES, Burg G et al (2005) WHOEORTC classification for cutaneous lymphomas. Blood 105(10): 3768–85 (doi: 10.1182/blood2004-09-3502)
LEARNING POINTS n T-cell lymphomas are divided into primary cutaneous and peripheral forms, with further subtypes of disease within these broad categories. n The clinical manifestations of each subtype may be similar and confuse the overall picture; however, an accurate diagnosis is crucial since it has implications for the patient and clinician in terms of prognosis and therapeutic decision making. n Pulmonary involvement by peripheral T-cell lymphoma is rare, particularly in isolation, and like other visceral manifestations can be associated with a worse long-term outcome. n More aggressive approaches to treating T-cell lymphoma should be actively considered in patients whose disease subtype or clinical picture suggests they are a high-risk case, although guidelines for treatment remain some way off as a result of the rarity of the condition.
BJHM A APP IS FREE TO DOWNLOAD FOR TABLET AND SMART PHONE USE
REGIS TODAY TER RECEIV AND FIRST ISE THE SU FREE E © 2014 MA Healthcare Ltd
EstablishEd 1966
Volume
2013 6 June 74 No
www.bjhm.co.uk
Volume 74 No 7 July 2013
m.co.uk
www.bjh d 1966
EstablishE
s l doctor The multispecialty review journal for hospital doctors for hospita journal y review
The BJHM app is free to download and you will also receive an issue of the journal free of charge. All issues published since then are available for purchase, and you can subscribe to ensure you don’t miss an issue. British Journal of Hospital Medicine is the leading monthly multi-specialty review journal for hospital doctors.
Ent onset: improvEm Editorials Quality improvEmEnt pain of acute Quality in patients with chest Experiences and challenges in achieving sustainable quality Widening indications for CRTtherapy implants: Burgess audit experienceMF Tang, Malcolm improvement in two UK hospitals not necessarily ‘theOxygen more the merrier’? single centre Garg, Joseph Sandra Fernandez-Caballero, Dubravka Becic, Irene Bouras, David Walker, practice A Scott,Pankaj David J Fox work in Rajiv Sankaranarayanan, Mark Lagan, Jakub Pervez Sultan bowel obstruction Eports Controversies in rectal cancer casE rEports casE r diverticulum causing small Nazir Michael J Hershman Alzein, Sarfraz Pain inreassured the neck: a rare complication of carbimazole therapy Giant Meckel’s Khalil, Abdulhalim falsely Aoff are we being Alex Ashman, Prashanth Vas, Suresh K Patel, Alison Melvin symposium on rEctal cancEr John Jeffery, infection: varicella chickenpox? Return of the spleens Who should be treating Neonatal rectal cancer inhistory 2013?of Hicks Sarah ST Umesh Bangalorelakshminarayana, Russell Patmore, Philip Dore, by a maternal Zengeya,
pecialt The multis s
Editorial Patient access
schemes:
making them
David Barber
Audit Project: National The Fifth for hospital doctors implications M Cook Jaideep
J Pandit,
Tim
m on
T Chris Thompson, J Graham Williams Stanley Siba P Paul,
symposiu HEaltH matErnal for healthy women Alina Vais,
Extra-levator abdomino-perineal excision in advanced low rectal cancer surgery
women care for Preconceptionhealth conditions with mental Peripartum Rhidian
Alina Vais,
appraise
Paul Taylor,
Charles
Hussain,
Amy
drug reactions
Colin Bigham,
Alison Elsey
aspEcts
Mark Davies
Cox
a systematic
Jamilla A
Cutaneous
Stacey
of
testing Interpreting syphilis serology
Michael J Hershman, Hassan Mohammad, Anwar Hussain, Awais Ahmed
Contact radiotherapy for elderly patients review with early low rectal cancers Gadoud
naevi Spider When and how does one refer a death toguide the coroner? a practical Ocular trauma: classification, surgery Death certification: after hepatic and prognosis management
A Sun Myint care
in intensive
rEviEw ip
Artificial hydration in the terminally ill patient management lEadErsH How to improve your curriculum vitae Postoperative
Helen O’Sullivan
03/06/2013
Elaine and Boland, Miriam Johnson, Jason Boland
self development leader Personality, the compassionate Judy McKimm,
Volume 74 No 7 July 2013
philia
Thrombo
Local excision of rectal tumours by minimally invasive woman the pregnant transanal surgery
Felicity Plaat,
rEviEws How to
patient A Papillon patient’s journey of the pre-eclamptic
Jones, Mark
trauma in
Brigid Hayden,
Sanjeev Dayal, Brendan Moran
Kate Harding
management
Jones, Sadie
Managing
6 74 No Volume June 2013
Sanjeev Dayal, Brendan Moran
Kate Lucinda Green,
Lucinda Green,
Radhakrishnan Jayan, Michael Greenstone
LOREC: the English Low Rectal Cancer National Development Programme
care conditions Preconception with medical Harding and those
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CTD_C97_cover.indd 1
11:48
01/07/2013 09:22
www.bjhm.co.uk
British Journal of Hospital Medicine, November 2014, Vol 75, No 11
653
h Journal of Hospital Medicine. Downloaded from magonlinelibrary.com by 139.080.123.051 on December 12, 2015. For personal use only. No other uses without permission. . All rights rese
A 72-year-old woman with a persistent cough and abnormal chest X-ray T-cell lymphomas are a form of lymphoproliferative disease broadly categorized as being either primary cutaneous or peripheral. There is considerable overlap in their clinical presentation, but confirming the precise disease subtype is critical since it has implications for prognosis and treatment strategy. Its rarity means guidelines for treatment are limited, with more aggressive approaches usually reserved for high risk or refractory cases. This article reports the case of a woman previously treated for presumed primary cutaneous T-cell lymphoma who developed isolated pulmonary recurrence at a 3-year interval – a rare finding in this condition and indicative of this actually being a form of peripheral T-cell lymphoma all along.
Discussion
T-cell lymphomas are a heterogeneous group of lymphoproliferative conditions. In broad terms, they are classified as primary cutaneous T-cell lymphomas or peripheral T-cell lymphomas. However, peripheral T-cell lymphoma can involve the skin and even present as isolated skin lesions, so there is considerable overlap. It is increasingly recognized that subtypes of cutaneous T-cell lymphoma and peripheral T-cell lymphoma are very different Dr John P Corcoran is Specialist Registrar in Respiratory Medicine, Dr Alastair J Moore is Consultant Respiratory Physician and Dr Ling-Pei Ho is Consultant Respiratory Physician in the Oxford Centre for Respiratory Medicine, Oxford University Hospitals NHS Trust, Churchill Hospital, Oxford OX3 7LE, Dr Susan J Davies is Consultant Pathologist in the Department of Cellular Pathology and Dr Graham P Collins is Consultant Haematologist in the Department of Clinical Haematology, Oxford University Hospitals NHS Trust, Oxford Correspondence to: Dr JP Corcoran ([email protected])
652
with respect to their clinical behaviour and response to treatment (Willemze et al, 2005). This has led to a separation of
those that display more benign behaviour, such as lymphomatoid papulosis and cutaneous anaplastic large cell lym-
Figure 1. a. Axial and (b) coronal computed tomography images demonstrating bilateral parenchymal and endobronchial nodularity with larger left lower and right middle lobe soft tissue masses.
a
b
Case Report
A 72-year-old woman was seen in clinic with a 3-month history of persistent dry cough and chest X-ray arranged by her GP that had demonstrated bilateral pulmonary nodules. The patient’s medical history was notable only for a skin cancer – labelled as a primary cutaneous T-cell lymphoma – diagnosed 3 years previously and successfully treated with excision biopsy and radiotherapy. Other than a persistent cough she described no concerning features including haemoptysis, weight loss, anorexia, dyspnoea or chest pain. She was a lifelong non-smoker with no occupational risk factors for lung disease. On examination the patient was afebrile with normal resting oxygen saturations. Cardiovascular and abdominal examinations were unremarkable; pulmonary examination revealed fine inspiratory crackles at the left base only. Routine bloods including full blood count, clotting screen, renal function, liver function and serum calcium were within normal limits. Computed tomography scan of the thorax (Figure 1) demonstrated a 5 cm soft tissue mass narrowing the left main bronchus with further smaller nodules visualized within the large airways and lung parenchyma bilaterally. Subsequent whole body positron emission tomography scan confirmed that pathological fludeoxyglucose uptake was confined to the thorax only. Flexible bronchoscopy identified multiple pink gelatinous lesions throughout the bronchial tree (Figure 2a) with the largest masses narrowing the left main and right middle lobe bronchi. Biopsies (Figures 2b and c) revealed infiltration of the bronchial mucosa with neoplastic cells strongly expressing CD30 and CD2, scattered staining for CD4 and negative for other markers including CD56, synaptophisin, cytokeratin, CD20 and ALK-1. MIB-1 proliferative index was greater than 80%. These immunohistochemistry results prompted comparison with the skin biopsy histology from 3 years previously, demonstrating morphological similarities and allowing confirmation of the diagnosis of recurrent peripheral T-cell lymphoma with isolated pulmonary disease. The patient underwent treatment with combination chemotherapy (six cycles of CHOP – cyclophosphamide, doxorubicin, vincristine and prednisolone) to complete remission and 1 year later remained systemically disease-free on interval positron emission tomography-computed tomography. She intermittently develops transient migratory skin lesions (consistent with a pattern of lymphomatoid papulosis) that have been biopsied and confirmed as CD30-positive peripheral T-cell lymphoma, and remains under long-term haematology outpatient follow up.
© 2014 MA Healthcare Ltd
Introduction
British Journal of Hospital Medicine, November 2014, Vol 75, No 11
h Journal of Hospital Medicine. Downloaded from magonlinelibrary.com by 139.080.123.051 on December 12, 2015. For personal use only. No other uses without permission. . All rights rese
Case Report involvement, associated with a worse prognosis. Treatment usually involves combination chemotherapy; more aggressive approaches such as autologous haemopoietic stem cell transplantation and radiation therapy are controversial and generally used in patients whose disease is either refractory or considered high risk on the basis of subtype and prognostic index (Sonnen et al, 2005). BJHM
a
c
b
Figure 2. a. Bronchoscopic view of distinct soft-tissue lesions in the mid-trachea. b and c. Haematoxylin and eosin stain of endobronchial biopsies showing infiltration of atypical lymphoid cells at (b) x10 and (c) x20 power.
phoma, from clinically aggressive forms including HTLV-1 positive adult T-cell lymphoma where the median survival is less than 6 months. Peripheral T-cell lymphoma is a rare condition which accounts for 10% of cases of non-Hodgkin lymphoma. This fact, in combination with the heterogeneity of the disease, has presented a significant challenge in developing guidelines. Collaborative work through the International peripheral T-cell lymphoma Project has compensated by combining data from multiple sources to inform the evidence base for both prognostic and therapeutic purposes (Foss et al, 2011), although individualized treatment strategies for patients remain some way off
(Moskowitz et al, 2012). Pulmonary and particularly endobronchial disease in the context of peripheral T-cell lymphoma is unusual and, as with other types of visceral
Foss FM, Zinzani PL, Vose JM et al (2011) Peripheral T-cell lymphoma. Blood 117(25): 6756–67 (doi: 10.1182/blood-2010-05-231548) Moskowitz AJ, Lunning MA, Horwitz SM (2012) Should patients with aggressive peripheral T-cell lymphoma all be treated the same?: no… well yes, …but maybe not for long. Cancer J 18(5): 445–9 (doi: 10.1097/PPO.0b013e31826aeeb2) Sonnen R, Schmidt WP, Muller-Hermelink HK, Schmitz N (2005) The International Prognostic Index determines the outcome of patients with nodal mature T-cell lymphomas. Br J Haematol 129(3): 366–72 (doi: 10.1111/j.1365-2141.2005.05478.x) Willemze R, Jaffe ES, Burg G et al (2005) WHOEORTC classification for cutaneous lymphomas. Blood 105(10): 3768–85 (doi: 10.1182/blood2004-09-3502)
LEARNING POINTS n T-cell lymphomas are divided into primary cutaneous and peripheral forms, with further subtypes of disease within these broad categories. n The clinical manifestations of each subtype may be similar and confuse the overall picture; however, an accurate diagnosis is crucial since it has implications for the patient and clinician in terms of prognosis and therapeutic decision making. n Pulmonary involvement by peripheral T-cell lymphoma is rare, particularly in isolation, and like other visceral manifestations can be associated with a worse long-term outcome. n More aggressive approaches to treating T-cell lymphoma should be actively considered in patients whose disease subtype or clinical picture suggests they are a high-risk case, although guidelines for treatment remain some way off as a result of the rarity of the condition.
BJHM A APP IS FREE TO DOWNLOAD FOR TABLET AND SMART PHONE USE
REGIS TODAY TER RECEIV AND FIRST ISE THE SU FREE E © 2014 MA Healthcare Ltd
EstablishEd 1966
Volume
2013 6 June 74 No
www.bjhm.co.uk
Volume 74 No 7 July 2013
m.co.uk
www.bjh d 1966
EstablishE
s l doctor The multispecialty review journal for hospital doctors for hospita journal y review
The BJHM app is free to download and you will also receive an issue of the journal free of charge. All issues published since then are available for purchase, and you can subscribe to ensure you don’t miss an issue. British Journal of Hospital Medicine is the leading monthly multi-specialty review journal for hospital doctors.
Ent onset: improvEm Editorials Quality improvEmEnt pain of acute Quality in patients with chest Experiences and challenges in achieving sustainable quality Widening indications for CRTtherapy implants: Burgess audit experienceMF Tang, Malcolm improvement in two UK hospitals not necessarily ‘theOxygen more the merrier’? single centre Garg, Joseph Sandra Fernandez-Caballero, Dubravka Becic, Irene Bouras, David Walker, practice A Scott,Pankaj David J Fox work in Rajiv Sankaranarayanan, Mark Lagan, Jakub Pervez Sultan bowel obstruction Eports Controversies in rectal cancer casE rEports casE r diverticulum causing small Nazir Michael J Hershman Alzein, Sarfraz Pain inreassured the neck: a rare complication of carbimazole therapy Giant Meckel’s Khalil, Abdulhalim falsely Aoff are we being Alex Ashman, Prashanth Vas, Suresh K Patel, Alison Melvin symposium on rEctal cancEr John Jeffery, infection: varicella chickenpox? Return of the spleens Who should be treating Neonatal rectal cancer inhistory 2013?of Hicks Sarah ST Umesh Bangalorelakshminarayana, Russell Patmore, Philip Dore, by a maternal Zengeya,
pecialt The multis s
Editorial Patient access
schemes:
making them
David Barber
Audit Project: National The Fifth for hospital doctors implications M Cook Jaideep
J Pandit,
Tim
m on
T Chris Thompson, J Graham Williams Stanley Siba P Paul,
symposiu HEaltH matErnal for healthy women Alina Vais,
Extra-levator abdomino-perineal excision in advanced low rectal cancer surgery
women care for Preconceptionhealth conditions with mental Peripartum Rhidian
Alina Vais,
appraise
Paul Taylor,
Charles
Hussain,
Amy
drug reactions
Colin Bigham,
Alison Elsey
aspEcts
Mark Davies
Cox
a systematic
Jamilla A
Cutaneous
Stacey
of
testing Interpreting syphilis serology
Michael J Hershman, Hassan Mohammad, Anwar Hussain, Awais Ahmed
Contact radiotherapy for elderly patients review with early low rectal cancers Gadoud
naevi Spider When and how does one refer a death toguide the coroner? a practical Ocular trauma: classification, surgery Death certification: after hepatic and prognosis management
A Sun Myint care
in intensive
rEviEw ip
Artificial hydration in the terminally ill patient management lEadErsH How to improve your curriculum vitae Postoperative
Helen O’Sullivan
03/06/2013
Elaine and Boland, Miriam Johnson, Jason Boland
self development leader Personality, the compassionate Judy McKimm,
Volume 74 No 7 July 2013
philia
Thrombo
Local excision of rectal tumours by minimally invasive woman the pregnant transanal surgery
Felicity Plaat,
rEviEws How to
patient A Papillon patient’s journey of the pre-eclamptic
Jones, Mark
trauma in
Brigid Hayden,
Sanjeev Dayal, Brendan Moran
Kate Harding
management
Jones, Sadie
Managing
6 74 No Volume June 2013
Sanjeev Dayal, Brendan Moran
Kate Lucinda Green,
Lucinda Green,
Radhakrishnan Jayan, Michael Greenstone
LOREC: the English Low Rectal Cancer National Development Programme
care conditions Preconception with medical Harding and those
1 CTD_C81_cover.indd
CTD_C97_cover.indd 1
11:48
01/07/2013 09:22
www.bjhm.co.uk
British Journal of Hospital Medicine, November 2014, Vol 75, No 11
653
h Journal of Hospital Medicine. Downloaded from magonlinelibrary.com by 139.080.123.051 on December 12, 2015. For personal use only. No other uses without permission. . All rights rese
