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Oncology

Haematology

Haematological malignancies (blood cancers) are the fifth most common cancer group in economically developed regions of the world. Traditionally, they are categorised by site according to whether cancer is first detected in the blood (leukaemias), lymph nodes (lymphomas – Hodgkin and non-Hodgkin) or bone (myelomas).¹

Solid tumors make up the majority of malignancies^2,3. They are mainly classified as carcinomas and sarcomas based on the type of cells they originate from. Solid tumors include common malignancies such as breast cancer, lung cancer and prostate cancer.

https://hmrn.org/about/classification
https://gco.iarc.fr/today
https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2019/cancer-facts-and-figures-2019.pdf

Oncology

Haematology

https://hmrn.org/about/classification
https://gco.iarc.fr/today
https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2019/cancer-facts-and-figures-2019.pdf

Today we know that cancer is not one single disease. It has over 200 different sub-types⁴, each with a unique molecular signature and different clinical expression.
Great advances in science have brought a revolution in cancer care. Survival rates are improving, and so is the quality of life of patients⁵.

4. https://www.cancerresearchuk.org/
5. https://www.worldwidecancerresearch.org/

Advanced / Metastatic
	Breast Cancer Breast cancer is the most common malignancy in women¹. In 2020, the estimated incidence was 355,457 cases in EU-27 and 7,772 cases in Greece². Approximately 1 in 11 women in the EU-27 will develop breast cancer before the age of 74².

Some of the most important risk factors are gender, age, genetic factors (BRCA), estrogen exposure, radiation, number of pregnancies, increased breast density and atypical hyperplasia³. Other lifestyle factors such as alcohol consumption, body weight, diet and exercise are likely to impact the potential risk^3,4.

Tumors are categorized based on histology and routine immunohistochemistry to better define the benefit from various treatments as well as prognosis. Key parameters examined are the histological type, the degree of differentiation, the expression of hormone receptors (ER, PR), the status of the HER2 receptor, the Ki67 index as well as the molecular signature^3,4.

Treatment options include local treatment (surgery and radiotherapy) as well as systemic treatment (hormone therapy, chemotherapy, anti-HER2 therapy, targeted therapies and immunotherapies)^3,4,5.

At the time of diagnosis, approximately 5-10% of tumors are metastatic, that is, the malignancy has spread from the primary site (the breast) to other parts of the body⁶.

Sources

ECIS-European Cancer Information System. https://ecis.jrc.ec.europa.eu/ , last accessed 3/7/2023.
Europa Donna Breast cancer facts. https://www.europadonna.org/breast-cancer/ ,last accessed 3/7/2023.
Cardoso F. et al. Early Breast Cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2019;30(8):1194-1220.
Θεραπευτικά πρωτόκολλα ΕΟΠΕ, 9η έκδοση. https://www.hesmo.gr/images/%CE%98%CE%B5%CF%81%CE%B1%CF%80%CE%B5%CF%85%CF%84%CE%B9%CE%BA%CE%AC_%CE%A0%CF%81%CF%89%CF%84%CF%8C%CE%BA%CE%BF%CE%BB%CE%BB%CE%B1_%CE%95%CE%9F%CE%A0%CE%95-9%CE%B7_%CE%88%CE%BA%CE%B4%CE%BF%CF%83%CE%B7_final_1.pdf ,last accessed 3/7/2023.
Gennari A. et al. ESMO Clinical Practice Guideline for the diagnosis, staging and treatment of patients with metastatic breast cancer. Ann. Oncol. 2021 Dec;32(12):1475-1495.
Europa Donna statistics/guidelines. https://www.europadonna.org/metastatic/statistics-guidelines/ ,last accessed 6/7/2023.


Advanced / Metastatic
	Breast Cancer Breast cancer is the most common malignancy in women¹. In 2020, the estimated incidence was 355,457 cases in EU-27 and 7,772 cases in Greece². Approximately 1 in 11 women in the EU-27 will develop breast cancer before the age of 74². Read More Some of the most important risk factors are gender, age, genetic factors (BRCA), estrogen exposure, radiation, number of pregnancies, increased breast density and atypical hyperplasia³. Other lifestyle factors such as alcohol consumption, body weight, diet and exercise are likely to impact the potential risk^3,4. Tumors are categorized based on histology and routine immunohistochemistry to better define the benefit from various treatments as well as prognosis. Key parameters examined are the histological type, the degree of differentiation, the expression of hormone receptors (ER, PR), the status of the HER2 receptor, the Ki67 index as well as the molecular signature^3,4. Treatment options include local treatment (surgery and radiotherapy) as well as systemic treatment (hormone therapy, chemotherapy, anti-HER2 therapy, targeted therapies and immunotherapies)^3,4,5. At the time of diagnosis, approximately 5-10% of tumors are metastatic, that is, the malignancy has spread from the primary site (the breast) to other parts of the body⁶. Sources ECIS-European Cancer Information System. https://ecis.jrc.ec.europa.eu/ , last accessed 3/7/2023. Europa Donna Breast cancer facts. https://www.europadonna.org/breast-cancer/ ,last accessed 3/7/2023. Cardoso F. et al. Early Breast Cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2019;30(8):1194-1220. Θεραπευτικά πρωτόκολλα ΕΟΠΕ, 9η έκδοση. https://www.hesmo.gr/images/%CE%98%CE%B5%CF%81%CE%B1%CF%80%CE%B5%CF%85%CF%84%CE%B9%CE%BA%CE%AC_%CE%A0%CF%81%CF%89%CF%84%CF%8C%CE%BA%CE%BF%CE%BB%CE%BB%CE%B1_%CE%95%CE%9F%CE%A0%CE%95-9%CE%B7_%CE%88%CE%BA%CE%B4%CE%BF%CF%83%CE%B7_final_1.pdf ,last accessed 3/7/2023. Gennari A. et al. ESMO Clinical Practice Guideline for the diagnosis, staging and treatment of patients with metastatic breast cancer. Ann. Oncol. 2021 Dec;32(12):1475-1495. Europa Donna statistics/guidelines. https://www.europadonna.org/metastatic/statistics-guidelines/ ,last accessed 6/7/2023.

Multiple

myeloma

Multiple myeloma is a neoplastic disease of plasma cells, a type of white blood cell that normally produces antibodies¹.

Multiple myeloma accounts for 1%-1.8% of all malignancies² and 10% of all hematological malignancies¹.

Diffuse Large

B-Cell Lymphoma (DLBCL)

DLBCL is the most common type of high-grade non-Hodgkin lymphoma, with nearly half of all cases of high-grade non-Hodgkin lymphoma being DLBCL¹.

Non-Hodgkin’s lymphoma (NHL) refers to a group of neoplasms of the lymphatic system with different characteristics, which originate from lymphocytes, a type of white blood cells involved in the body’s immune system².

There are different subtypes of DLBCL, e.g. germinal center or activated B cell, while there are also some rare types of DLBCL^1,3.

About half of patients diagnosed with DLBCL are over 60 years of age at the time of diagnosis³, but the disease can develop at any age¹.

DLBCL is slightly more common in men¹. The prevalence in Europe is 3-4 new patients per 100,000 population⁴.

Often, the first symptom of DLBCL is a painless, rapidly growing lump in the neck, armpit, or groin area, which is caused by an enlarged lymph node⁵.

Other symptoms may include night sweats, fever, unexplained weight loss, while patients may also notice fatigue, loss of appetite, shortness of breath, aches, itchy skin, persistent or recurring infections^5,6.

Diagnosis can be difficult⁶ and involves biopsy, blood tests and imaging tests^5,6, the results of which determine the staging, grade and subtype of DLBCL^5,6.

There are various treatments available for DLBCL, the choice of which will depend on many factors including DLBCL subtype, stage and grade of DLBCL, age, overall health, other treatments for either DLBCL or other diseases⁵.

DLBCL can be cured in almost half of patients⁷.

Sources

http://pathophysiology2.med.uoa.gr/fileadmin/pathophysiology.med.uoa.gr/uploads/RECONET-DIACHYTO_LEMFOMA_APO_MEGALA_B-KYTTARA_ELLINIKA.pdf
Leukemia & Lymphoma Society. NHL. http://www.lls.org/lymphoma/non-hodgkin-lymphoma?src1=20045&src2. Accessed 13 May 2022
Cancer.net. Lymphoma – Non-Hodgkin: Subtypes. http://www.cancer.net/cancer-types/lymphoma-non-hodgkin/subtypes. Accessed 13 May 2022.
Li S, Young KH, Medeiros LJ. Diffuse large B-cell lymphoma. Pathology 2018;50 (1):74–87.
Lymphoma Research Foundation. Understanding Diffuse Large B-Cell Lymphoma. LRF_Factsheet_Diffuse_Large_B_Cell_ Lymphoma.pdf. Accessed 13 May 2022
https://www.lymphoma.org.au/el/types-of-lymphoma/non-hodgkin-lymphoma/aggressive-fast-growing-b-cell-nhl/
diffuse-large-b-cell-dlbcl/
https://www.cancer.org/cancer/types/non-hodgkin-lymphoma/treating/b-cell-lymphoma.html

Mantle cell

lymphoma

Mantle cell lymphoma is a rare hematologic malignancy classified among non-Hodgkin lymphomas (NHL). It represents approximately 4% of all cancers and accounts for 3-10% of all NHL cases, making it an atypical form of NHL. The annual incidence is 0.5-1 new case per 100,000 population¹.

Although the disease is more common in men over 60 years old, it can be diagnosed in women and individuals of all ages².

High risk
	Neuroblastoma Neuroblastoma is the most common extracranial solid tumor of childhood. In approximately 90% of cases, the diagnosis is made at an age younger than 5 years, with a median age of diagnosis at 17 months¹.


High risk
	Neuroblastoma Neuroblastoma is the most common extracranial solid tumor of childhood. In approximately 90% of cases, the diagnosis is made at an age younger than 5 years, with a median age of diagnosis at 17 months¹. Read More This is a malignancy that primarily originates from neural tissue found in the adrenal glands, neck, thorax, and the spinal cord². Neuroblastomas are classified into very low risk/low risk, intermediate risk, and high-risk categories, based on various factors such as age, histology, degree of differentiation, the number of MYCN copies^3,1. For the treatment of high-risk neuroblastomas, chemotherapy, surgery, bone marrow transplantation, radiation therapy, retinoids, and immunotherapy can be used⁴. Sources Neuroblastoma Treatment (PDQ®)–Health Professional Version. https://www.cancer.gov/types/neuroblastoma/hp/neuroblastoma-treatment-pdq ,last accessed 6/7/2023 SIOP Europe main types of paediatric cancers. https://siope.eu/parents-and-patients/general-information-on-clinicaltrials/main-types-paediatric-cancer/ ,last accessed 6/7/2023 Irwin MS. et al. Revised Neuroblastoma Risk Classification System: A Report From the Children’s Oncology Group. J Clin Oncol. 2021 Oct 10;39(29):3229-3241. Treatment by risk group for neuroblastoma. https://www.cancerresearchuk.org/about-cancer/childrens-cancer/neuroblastoma/treatment-risk-group ,last accessed 6/7/2023.

Castleman’s

Disease

Castleman’s disease is a rare disorder that shares common lymph node histological features. There are two clinical entities described: unicentric, involving a single lymph node, and multicentric, characterized by generalized lymphadenopathy and a more aggressive clinical course¹.

Although the etiology of multicentric disease is unknown, interleukin-6 (IL-6) is a confirmed risk factor for the disease in approximately one-third of patients².

The Castleman Disease Collaborative Network (CDCN) is investigating four hypotheses that could be linked to the etiology, including autoimmune, inflammatory, neoplastic, and pathogenetic mechanisms^3,7.

Human herpesvirus 8 (HHV8) causes multicentric Castleman’s disease in immunosuppressed patients, while in patients not affected by HHV8, the disease is considered idiopathic^1,5.

The epidemiology of multicentric Castleman’s disease has not been widely studied. Men appear to be affected more frequently than women. The average age of diagnosis is during the patient’s sixth decade of life, but the disease can occur at any age, even in young children^11,14.

The disease presents with different forms, with some patients having mild non-specific symptoms, while others may develop multi-organ failure or even a fatal outcome^9,10.

Diagnosis is based on clinical examination, biopsy, as well as laboratory and imaging tests¹⁶.
Treatment includes surgical intervention and/or radiation therapy and pharmacological management¹⁶.

Sources

Amel El Korbi et al. PAMJ – 37(369). 22 Dec 2020
Sheila K. Pierson Blood Adv (2021) 5 (17): 3445–3456
Fajgenbaum DC, van Rhee F , Nabel CS . HHV-8-negative, idiopathic multicentric Castleman disease: novel insights into biology, pathogenesis, and therapy . Blood . 2014 ;123 (19 ):2924 -2933
Yoshizaki K , Matsuda T , Nishimoto N , et al. Pathogenic significance of interleukin-6 (IL-6/BSF-2) in Castleman’s disease . Blood . 1989 ;74 (4 ):1360 -1367
Nishimoto N , Terao K , Mima T , Nakahara H , Takagi N , Kakehi T . Mechanisms and pathologic significances in increase in serum interleukin-6 (IL-6) and soluble IL-6 receptor after administration of an anti-IL-6 receptor antibody, tocilizumab, in patients with rheumatoid arthritis and Castleman disease . Blood . 2008 ;112 (10 ):3959 -3964
Stone K , Woods E , Szmania SM , et al. Interleukin-6 receptor polymorphism is prevalent in HIV-negative Castleman Disease and is associated with increased soluble interleukin-6 receptor levels . PLoS One . 2013 ;8 (1 ):e54610
Fajgenbaum DC , Ruth JR , Kelleher D , Rubenstein AH . The collaborative network approach: a new framework to accelerate Castleman’s disease and other rare disease research . Lancet Haematol . 2016 ;3 (4 ):e150 -e152
Iwaki N , Sato Y , Takata K , et al. Atypical hyaline vascular-type castleman’s disease with thrombocytopenia, anasarca, fever, and systemic lymphadenopathy . J Clin Exp Hematop . 2013 ;53 (1):87-93
Iwaki N Fajgenbaum DC , Nabel CS , et al. Clinicopathologic analysis of TAFRO syndrome demonstrates a distinct subtype of HHV-8-negative multicentric Castleman disease Am J Hematol. 2016 ;91 (2):220-226
Kawabata H , Kotani S , Matsumura Y , et al. Successful treatment of a patient with multicentric Castleman’s disease who presented with thrombocytopenia, ascites, renal failure and myelofibrosis using tocilizumab, an anti-interleukin-6 receptor antibody . Intern Med. 2013 ;52 (13):1503-1507
Frizzera G, Banks PM , Massarelli G , Rosai J . A systemic lymphoproliferative disorder with morphologic features of Castleman’s disease. Pathological findings in 15 patients Am J Surg Pathol. 1983 ;7 (3):211 -231
Bowne WB , Lewis JJ , Filippa DA , et al. The management of unicentric and multicentric Castleman’s disease: a report of 16 cases and a review of the literature . Cancer . 1999 ;85 (3):706-717
Chronowski GM , Ha CS , Wilder RB , Cabanillas F , Manning J, Cox JD .Treatment of unicentric and multicentric Castleman disease and the role of radiotherapy. Cancer. 2001 ;92 (3):670-676
Parez N , Bader-Meunier B , Roy CC, Dommergues JP. Paediatric Castleman disease: report of seven cases and review of the literature. Eur J Pediatr. 1999;158 (8):631-637
https://www.thelancet.com/journals/lanhae/article/PIIS2352-3026(16)00006-5/fulltext
Dispenzieri A, Fajgenbaum DC Blood (2020) 135 (16): 1353–1364.

Blastic Plasmacytoid

Dendritic
Cell Neoplasm (BPDCN)

BPDCN is a rare hematological cancer that belongs to the category of acute myeloid leukemias and related neoplasms¹. It represents 0.44% of new hematological malignancies each year, which means a prevalence of 0.04 new patients per 100,000 population, thus approximately 700 new patients in the United States and about 1,000 new patients in Europe².

BPDCN more commonly affects patients over the age of 60, but cases have been recorded in young individuals under the age of 20, as well as in children.^2,3,4,5.
The etiology of BPDCN is not known. Recent studies have shown that the neoplasm initially appears in the skin and subsequently disseminates to the bone marrow. Both at diagnosis and during the course of the disease’s flares and remissions, continuous genetic mutations are detected in the skin or bone marrow.^3,6-9.
Dermatologists are usually the first to come in contact with BPDCN patients, as skin lesions are the hallmark of the disease. The lesions are heterogeneous and may be isolated or widespread, scattered over a wide range^10-14.
The diagnosis of BPDCN is primarily based on the immunophenotype of leukemic cells in samples from the skin, blood, and bone marrow¹⁵.

The prognosis for the disease is poor².

Arber DA, Orazi A, Hasserjian R et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood 2016;127:2391–2405.
Guru Murthy GS, Pemmaraju N, Atallah E. Epidemiology and survival of blastic plasmacytoid dendritic cell neoplasm. Leuk Res 2018;73: 21–3.
Venugopal S, Zhou S, El Jamal SM et al. Blastic plasmacytoid dendritic cell neoplasm – current insights. Clin Lymphoma Myeloma Leuk 2019;19:545–54.
Jegalian AG, Buxbaum P, Facchetti F et al. Blastic plasmacytoid dendritic cell neoplasm in children: diagnostic features and clinical implications. Haematologica 2010;95:1873–9.
Li Y, Sun V, Sun W, Pawlowska A. Blastic plasmacytoid dendritic cell neoplasm in children. Hematol Oncol Clin North Am 2020;34:601–12.
Sakamoto K, Takeuchi K. Cytogenetics of blastic plasmacytoid dendritic cell neoplasm: chromosomal rearrangements and DNA copynumber alterations. Hematol Oncol Clin North Am 2020;34:523–38.
Laribi K, Denizon N, Ghnay H et al. Blastic plasmacytoid dendritic cell neoplasm: the first report of two cases treated by 5-azacytidine. Eur J Haematol 2014;93:81–5.
Riaz W, Zhang L, Horna P, Sokol L. Blastic plasmacytoid dendritic cell neoplasm: update on molecular biology, diagnosis, and therapy. Cancer Control 2014;21:279–89.
Sapienza MR, Pileri S. Molecular features of blastic plasmacytoid dendritic cell neoplasm: DNA mutations and epigenetics. Hematol Oncol Clin North Am 2020;34:511–21.
Hirner JP, O’Malley JT, LeBoeuf NR. Blastic plasmacytoid dendritic cell neoplasm: the dermatologist’s perspective. Hematol Oncol Clin North Am 2020;34:501–9.
Garnache-Ottou F, Vidal C, Biichlé S et al. How should we diagnose and treat blastic plasmacytoid dendritic cell neoplasm patients? Blood Adv 2019;3:4238–51.
Deconinck E, Petrella T, Garnache Ottou F. Blastic plasmacytoid dendritic cell neoplasm: clinical presentation and diagnosis. Hematol Oncol Clin North Am 2020;34: 491–500.
Julia F, Dalle S, Duru G et al. Blastic plasmacytoid dendritic cell neoplasms: clinicoimmunohistochemical correlations in a series of 91 patients. Am J Surg Pathol 2014;38:673–80.
ulia F, Petrella T, Beylot-Barry M et al. Blastic plasmacytoid dendritic cell neoplasm: clinical features in 90 patients. Br J Dermatol 2013;169: 579–86.
Pagano L, Valentini CG, Grammatico S, Pulsoni A. Blastic plasmacytoid dendritic cell neoplasm: diagnostic criteria and therapeutical approaches. Br J Haematol. 2016;174(2):188–202

Ototoxicity
	in Oncology Patients Cisplatin is a fundamental therapeutic agent for the treatment of various pediatric solid malignancies, leading to increased survival in these patient¹. This therapeutic agent can lead to ototoxicity, which may manifest as hearing loss, ringing in the ears (tinnitus), and/or dizziness².


Ototoxicity
	in Oncology Patients Cisplatin is a fundamental therapeutic agent for the treatment of various pediatric solid malignancies, leading to increased survival in these patients¹. This therapeutic agent can lead to ototoxicity, which may manifest as hearing loss, ringing in the ears (tinnitus), and/or dizziness². Read More Cisplatin-induced ototoxicity results from the destruction of the hair cells in the cochlea and initially affects high frequencies. It is typically bilateral, irreversible and progressive². There are international recommendations that suggest assessing auditory function based on age and risk factors, using hearing tests such as pure-tone audiometry, auditory brainstem response (ABR) testing, and otoacoustic emissions³. Sources Chattarah A. et al. Cisplatin-Induced Ototoxicity: A Concise Review of the Burden, Prevention, and Interception Strategies. JCO Oncol. Pract. 2023;19(5):278-283 Landier W. et al. Ototoxicity and Cancer therapy. Cancer 2016;122(11):1647-1658. Meijer J. M. et al. Recommendations for Age-Appropriate Testing, Timing, and Frequency of Audiologic Monitoring During Childhood Cancer Treatment. JAMA Oncol 2021;7(10):1550-1558.doi:10.1001/jamaoncol.2021.2697.

This information is intended for public awareness purposes only and, under no circumstances, can it replace the advice of a doctor or another qualified healthcare professional.

Therapeutic

Areas

Oncology

Hematology

Rare and Genetic
Metabolic Diseases

Wound

Care

Oncology

Hematology

Rare and Genetic
Metabolic Diseases

Wound

Care

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