Hodgkin or Non-Hodgkin LymphomaHL PAX5- 2025NCT07313943
PAX5-NEGATIVE HODGKIN-LIKE LYMPHOMAS: A DIAGNOSTIC CHALLANGE
An observational study of Hodgkin or Non-Hodgkin Lymphoma, run by IRCCS Azienda Ospedaliero-Universitaria di Bologna at 2 sites in 2 countries.
Trial summary
Hodgkin lymphoma (HL) is a lymphoma that arises from peripheral B lymphocytes. However, the neoplastic cells, Hodgkin cells and Reed-Sternberg cells, typically lack most B-cell markers, usually preserving the expression of the transcriptional factor PAX5, only phenotypic clue of B-cell origin. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hodgkin or Non-Hodgkin Lymphoma
- How many people
- 60 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 30 Dec 2025to 30 Dec 2027
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: It is planned to enroll patients who have referred for diagnosis, from January 2014 to March 2025, at the following hospitals: 1) SSD of Hemolymphopathology IRCCS - Azienda Ospedaliero-Universitaria di Bologna Policlinico S. Orsola-Malpighi and 2) the Pathological Anatomy of Tübingen, Germany
Who may be able to join
- Patients with lymphoma diagnosed as classic Hodgkin's lymphoma with a negative PAX5 marker
- Patients with uncertain differential diagnosis between classical Hodgkin's lymphoma with atypical phenotype (PAX5 negative) and ALK-negative anaplastic large T-cell lymphoma (PAX5 negative)
- Adult males and females at diagnosis
- Availability of the molecular and/or cytogenetic data.
Who cannot join
- Patients with a diagnosis other than that under study, for whom clinical/histological/molecular information is not available
Trial locations and contacts
2 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
2 sites in 2 countries
Germany1 site, 1 recruiting
- Recruiting
Universitätsklinikum Tübingen Institut für Pathologie
Tübingen, 72076
Falko Fend, MD/PROF, 07071 29-82266, falko.fend@med.uni-tuebingen.de
Italy1 site, 1 recruiting
- Recruiting
Irccs Azienda Ospedaliero-Universitaria Di Bologna
Bologna, 40138
ELENA SABATTINI, MD, +390512144562, elena.sabattini@aosp.bo.it
GIOVANNA MOTTA, BS, 0512143045, giovanna.motta@aosp.bo.it
About this study
Official title: ANALISI DEI LINFOMI CON ASPETTO TIPO-HODGKIN A FENOTIPO ATIPICO PAX5 NEGATIVO
Hodgkin lymphoma (HL) is a lymphoma that arises from peripheral B lymphocytes. However, the neoplastic cells, Hodgkin cells and Reed-Sternberg cells, typically lack most B-cell markers, usually preserving the expression of the transcriptional factor PAX5, only phenotypic clue of B-cell origin.
Morphologically similar cells to those diagnostic Hodgkin and Reed-Sternberg cells can also be observed in other lymphocytic proliferations, including Anaplastic Large Cell Lymphoma (ALCL), which originates from T lymphocytes and which share many features with HL, like strong CD30 expression and usually loss of T-cell markers. However, their clinical course is dramatically different with curability rates of >90% for classical HL and an unfavorable prognosis for ALCL.
Read more
PAX5 expression in HL and cytotoxic molecules expression in ALCL tumor cells may be a useful aid for diagnosis. However, in some cases the differential diagnosis is difficult owing to absence of these established markers. Furthermore, clonality analyses on classical HL were focused on Ig regions while TCR clonality has not yet been usefully explored.
Studying the TCR clonal status of tumor cells, correlating it with a more comprehensive immunophenotypic profile and investigating the presence or absence of characteristic rearrangements (such as the JAK2 rearrangement, typical of ALCL lymphomas) could help to resolve the immuno-morphological overlap of the two entities and identify a possible repetitive pattern based on morphological, phenotypic and genetic characteristics.
To this aim we intend to involve the Pathological Anatomy of Tubinga to increase the number of cases and achieve statistical significance, given the relative rarity of this entity
Read the detailed description
Hodgkin lymphoma (HL) is a lymphoma that originates from peripheral B lymphocytes. However, the neoplastic Hodgkin and Reed-Sternberg cells typically lack most B-cell markers, including CD20, CD79a, CD19, Oct2, and BOB1, and retain only the transcription factor regulating B-cell differentiation, BSAP, encoded by the PAX5 gene. This antigen is generally expressed at a weaker intensity compared to that observed in small reactive B lymphocytes, which serve as internal controls ensuring adequate staining. Moreover, not all neoplastic cells show positivity for PAX5. For this reason, PAX5 immunoreactivity represents the only phenotypic clue to the B-cell origin of classical Hodgkin lymphomas.
The diagnosis of HL is relatively straightforward when this phenotype is present and coexists with other immunomorphological features such as CD30 and CD15 positivity and negativity for B- and T-cell lineage markers, cytotoxic markers, and EMA.
Morphologically similar Hodgkin and Reed-Sternberg-like cells can also be observed in other lymphoid proliferations, including anaplastic large cell lymphoma (ALCL), a lymphoma that also shares with HL a strong expression of CD30.³ ALCL originates from T lymphocytes but, similarly to HL, is highly defective in lineage-specific marker expression, often lacking T-cell markers or expressing only a subset of them. As a cytotoxic T-cell lymphoma, it frequently expresses perforin and typically shows aberrant expression of an epithelial antigen (EMA). Two genetic variants of ALCL exist: one carrying a translocation involving the ALK gene, detectable in tissue by immunohistochemistry, and the ALK-negative variant, which is considerably more challenging to diagnose. Further contributing to diagnostic complexity, ALCL may exhibit architectural patterns and morphology resembling those of HL, to the extent that the WHO classification recognizes a morphological "Hodgkin-like" subtype within ALK-positive ALCL.
In diagnostic practice, rare cases are encountered that morphologically resemble classical HL but are PAX5-negative; these cases may coexpress T-cell markers such as CD3 or CD8, cytotoxic markers (e.g., perforin), and EMA and/or show clonal rearrangement of T-cell receptor genes.⁵ Some reported cases have subsequently developed a true T-cell lymphoma and/or exhibited more frequent relapses, resembling HL cases with poorer prognosis. In some of these cases, rearrangement of the JAK2 gene has been described, a genetic alteration more typically associated with ALCL.
Given the potential immunomorphological overlap between PAX5-negative HL and ALK-negative ALCL, we aim to collect these rare cases to assess whether a recurring pattern of morphological, phenotypic, and genetic features can be identified, based on the data used to establish the diagnosis.
The study is observational, multicenter, international, prospective and retrospective
- Conditions
- Hodgkin or Non-Hodgkin Lymphoma
- Medical subject headings
- Lymphoma, Non-Hodgkin
What is being measured
The primary outcome is the main question the study is designed to answer.
Atypical Hodgkin Lymphoma
To identify a characteristic morphological, phenotypic, and genetic pattern for lymphoma cases with an atypical Hodgkin lymphoma and to determine whether there are areas of overlap with ALK-negative anaplastic large cell lymphoma.
Measured: 6/12/24 months
Secondary outcomes (1)
Clinical-pathological correlations
To perform clinical-pathological correlations (OS, PFS, possible therapy and response to therapy)
Measured: 6/12/24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jan 2026
- Study start30 Dec 2025 (estimated)
- Primary completion28 Feb 2026 (estimated)
- Study completion30 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hodgkin or Non-Hodgkin LymphomaStudies of the same condition, open and under way.
- More trials run by IRCCS Azienda Ospedaliero-Universitaria di BolognaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Other
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Elena Sabattini, IRCCS Azienda Ospedaliero-Universitaria di Bologna
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07313943
- Sponsor's protocol ID
- HL PAX5- 2025
- Acronym
- HL PAX5- 2025
- Status last verified
- Dec 2025
- First submitted
- 18 Dec 2025
- Last updated
- 2 Jan 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- ANALISI DEI LINFOMI CON ASPETTO TIPO-HODGKIN A FENOTIPO ATIPICO PAX5 NEGATIVO
- ClinicalTrials.gov ID
- NCT07313943
- Acronym / sponsor ID
- HL PAX5- 2025 / HL PAX5- 2025
- Conditions
- Hodgkin or Non-Hodgkin Lymphoma
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- IRCCS Azienda Ospedaliero-Universitaria di BolognaUniversity, hospital or other
- Study start
- 30 Dec 2025 (estimated)
- Primary completion
- 28 Feb 2026 (estimated)
- Study completion
- 30 Dec 2027 (estimated)
- First posted
- 2 Jan 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Hodgkin lymphoma (HL) is a lymphoma that arises from peripheral B lymphocytes. However, the neoplastic cells, Hodgkin cells and Reed-Sternberg cells, typically lack most B-cell markers, usually preserving the expression of the transcriptional factor PAX5, only phenotypic clue of B-cell origin.
Morphologically similar cells to those diagnostic Hodgkin and Reed-Sternberg cells can also be observed in other lymphocytic proliferations, including Anaplastic Large Cell Lymphoma (ALCL), which originates from T lymphocytes and which share many features with HL, like strong CD30 expression and usually loss of T-cell markers. However, their clinical course is dramatically different with curability rates of >90% for classical HL and an unfavorable prognosis for ALCL.
PAX5 expression in HL and cytotoxic molecules expression in ALCL tumor cells may be a useful aid for diagnosis. However, in some cases the differential diagnosis is difficult owing to absence of these established markers. Furthermore, clonality analyses on classical HL were focused on Ig regions while TCR clonality has not yet been usefully explored.
Studying the TCR clonal status of tumor cells, correlating it with a more comprehensive immunophenotypic profile and investigating the presence or absence of characteristic rearrangements (such as the JAK2 rearrangement, typical of ALCL lymphomas) could help to resolve the immuno-morphological overlap of the two entities and identify a possible repetitive pattern based on morphological, phenotypic and genetic characteristics.
To this aim we intend to involve the Pathological Anatomy of Tubinga to increase the number of cases and achieve statistical significance, given the relative rarity of this entity
Detailed description
Hodgkin lymphoma (HL) is a lymphoma that originates from peripheral B lymphocytes. However, the neoplastic Hodgkin and Reed-Sternberg cells typically lack most B-cell markers, including CD20, CD79a, CD19, Oct2, and BOB1, and retain only the transcription factor regulating B-cell differentiation, BSAP, encoded by the PAX5 gene. This antigen is generally expressed at a weaker intensity compared to that observed in small reactive B lymphocytes, which serve as internal controls ensuring adequate staining. Moreover, not all neoplastic cells show positivity for PAX5. For this reason, PAX5 immunoreactivity represents the only phenotypic clue to the B-cell origin of classical Hodgkin lymphomas.
The diagnosis of HL is relatively straightforward when this phenotype is present and coexists with other immunomorphological features such as CD30 and CD15 positivity and negativity for B- and T-cell lineage markers, cytotoxic markers, and EMA.
Morphologically similar Hodgkin and Reed-Sternberg-like cells can also be observed in other lymphoid proliferations, including anaplastic large cell lymphoma (ALCL), a lymphoma that also shares with HL a strong expression of CD30.³ ALCL originates from T lymphocytes but, similarly to HL, is highly defective in lineage-specific marker expression, often lacking T-cell markers or expressing only a subset of them. As a cytotoxic T-cell lymphoma, it frequently expresses perforin and typically shows aberrant expression of an epithelial antigen (EMA). Two genetic variants of ALCL exist: one carrying a translocation involving the ALK gene, detectable in tissue by immunohistochemistry, and the ALK-negative variant, which is considerably more challenging to diagnose. Further contributing to diagnostic complexity, ALCL may exhibit architectural patterns and morphology resembling those of HL, to the extent that the WHO classification recognizes a morphological "Hodgkin-like" subtype within ALK-positive ALCL.
In diagnostic practice, rare cases are encountered that morphologically resemble classical HL but are PAX5-negative; these cases may coexpress T-cell markers such as CD3 or CD8, cytotoxic markers (e.g., perforin), and EMA and/or show clonal rearrangement of T-cell receptor genes.⁵ Some reported cases have subsequently developed a true T-cell lymphoma and/or exhibited more frequent relapses, resembling HL cases with poorer prognosis. In some of these cases, rearrangement of the JAK2 gene has been described, a genetic alteration more typically associated with ALCL.
Given the potential immunomorphological overlap between PAX5-negative HL and ALK-negative ALCL, we aim to collect these rare cases to assess whether a recurring pattern of morphological, phenotypic, and genetic features can be identified, based on the data used to establish the diagnosis.
The study is observational, multicenter, international, prospective and retrospective
Study design
- Observational model
- Cohort
- Time perspective
- Other
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- It is planned to enroll patients who have referred for diagnosis, from January 2014 to March 2025, at the following hospitals: 1) SSD of Hemolymphopathology IRCCS - Azienda Ospedaliero-Universitaria di Bologna Policlinico S. Orsola-Malpighi and 2) the Pathological Anatomy of Tübingen, Germany
Key inclusion criteria (4 listed)
- Patients with lymphoma diagnosed as classic Hodgkin's lymphoma with a negative PAX5 marker
- Patients with uncertain differential diagnosis between classical Hodgkin's lymphoma with atypical phenotype (PAX5 negative) and ALK-negative anaplastic large T-cell lymphoma (PAX5 negative)
- Adult males and females at diagnosis
- Availability of the molecular and/or cytogenetic data.
Key exclusion criteria (1 listed)
- Patients with a diagnosis other than that under study, for whom clinical/histological/molecular information is not available
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Atypical Hodgkin Lymphoma
Time frame: 6/12/24 months
To identify a characteristic morphological, phenotypic, and genetic pattern for lymphoma cases with an atypical Hodgkin lymphoma and to determine whether there are areas of overlap with ALK-negative anaplastic large cell lymphoma.
1 secondary outcome
Clinical-pathological correlations
Time frame: 6/12/24 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jan 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Hodgkin or Non-Hodgkin Lymphoma, run by IRCCS Azienda Ospedaliero-Universitaria di Bologna at 2 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 2 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Germany, Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact ELENA SABATTINI, MD (+390512144562, elena.sabattini@aosp.bo.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Atypical Hodgkin Lymphoma (time frame: 6/12/24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jan 2026.