Single-cell analysis of CD30+ cells in lymphomatoid papulosis demonstrates a common clonal T-cell origin

Steinhoff, Matthias; Hummel, Michael; Anagnostopoulos, Ioannis; Kaudewitz, Peter; Seitz, Volkhard; Assaf, Chalid; Sander, Christian; Stein, Harald

doi:10.1182/blood-2001-12-0199

Cited by 78 publications

(50 citation statements)

References 32 publications

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“…For this typically waxing and waning skin lesion it is well documented that malignant progression occurs . It has further been shown that this skin neoplasm definitely is a monoclonal T-cell disorder of atypical CD30 + cells (Steinhoff et al, 2002) and that these atypical cells are even functionally linked to malignant progression (Levi et al, 2000).…”

Section: Discussionmentioning

confidence: 97%

Carcinoma-like vascular density in atypic keratoacanthoma suggests malignant progression

et al. 2002

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Differential diagnosis between keratoacanthomas and well differentiated squamous cell carcinomas based on clinical and histomorphological data is problematic. Recent findings of cellular atypia in a large proportion of keratoacanthomas indicated that these potentially 'self-healing' cutaneous neoplasms had the potential for malignant progression. Another malignancyassociated criterion is enhanced angiogenesis with increased microvessel density. To provide further diagnostic markers for keratoacanthomas we examined microvessel density on paraffin sections of 13 keratoacanthomas in comparison with 10 normal skin biopsies and 16 late-stage skin squamous cell carcinomas by counting and by computer-assisted image analysis of CD31-immunostained vessels. A significant increase of microvessel density in 'hot spots' was observed in keratoacanthomas as compared to normal skin. Furthermore, when keratoacanthomas were subdivided into tumours with and without malignancyassociated atypic areas, only those with atypia (n=6) were significantly better vascularised than normal skin and had a mean microvessel density in the range of late-stage squamous cell carcinomas. Both keratoacanthoma subtypes revealed comparable levels of inflammatory cell infiltration, tumour cell proliferation and vascular endothelial growth factor expression (mRNA and protein). Thus, in addition to malignancy-associated cellular atypia, increased microvessel density may serve as further diagnostic parameter to discriminate keratoacanthomas with a potential to progress to malignancy.

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Section: Discussionmentioning

confidence: 97%

Carcinoma-like vascular density in atypic keratoacanthoma suggests malignant progression

et al. 2002

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“…The lowest frequency of clonality (14.3%, 1 out of 7 samples) was detected in the case of lymphomatoid papulosis (LyP). LyP represents an intriguing cutaneous T-cell proliferation with a benign clinical course but with a histologic appearance reminiscent of malignant lymphoma 55 . It is known that some clinically benign proliferations have a clonal origin 15 .…”

Section: Discussionmentioning

confidence: 99%

Clonality testing of lymphoproliferative disorders in a large cohort of primary and consultant biopsies

Šváchová¹,

Tichý²,

Flodr³

et al. 2017

BIOMED PAP

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Background. Lymphoproliferative disease often presents the clinician and pathologist with a diagnostic dilemma, particularly in the early course of the disease. Methods. We used modified BIOMED-2 protocols to detect monoclonal expansions of immunoglobulin heavy chain (IgH) and T-cell receptor (TCR) genes in 957 formalin-fixed paraffin-embedded samples from 717 patients. To eliminate false-positive results, heteroduplex analysis was used after PCR reactions. The impact of different fixatives on DNA quality and performance of PCR was assessed. Results. In the class of B lymphomas we detected clonal IgH rearrangement in nearly 80% of cases and in the class of T lymphomas in 64% of cases. Performance of the assays was 94.7% and 92.5% for IgH and TCR clonality, respectively. Clonality rates in various B and T lymphomas were in concordance with previous studies. We also present 10 difficult cases where PCR analysis of IgH and TCR gene rearrangements significantly contributed to a decision on the correct diagnosis. Conclusion. These results confirm that the PCR-based analysis is suitable as a routine method and is helpful in establishing a diagnosis in morphologically unclear cases.

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“…Die bei LyP bis zu monatelangen Phasen der klinischen Erscheinungsfreiheit vor erneuter klinischer Manifestation weisen auf eine klinisch stumme Persistenz des T-Zell-Klons hin [14,20]. Zu den möglichen Kompartimenten, in denen der Zellklon persistieren könnte, ist neben Haut, Blut und Lymphknoten ebenfalls das Knochenmark anzuführen [26].…”

Section: Pathogenese Und Mechanismen Der Klinischen Regression Und Prunclassified

“…Einerseits könnte es sich bei der LyP um ein Kontinuum aus einer zunächst poly-/oligoklonalen Erkrankung handeln, die sich in 10 ± 20 % der Fälle zu einer klonalen malignen T-Zell-Proliferation mit möglichem Um diese Fragen zu klären und dabei erwähnte methodische Probleme zu umgehen, wurde die T-Zell-Rezeptor-g-Umlagerung einzelner mikrodissezierter sowohl CD30-positiver als auch CD30-negativer T-Lymphozyten isoliert aus Läsionen von klassischen Patienten mit LyP ohne assoziiertem malignen Lymphom analysiert (Abb. 3) [20]. Diese Untersuchung von 14 Hautbiopsaten von 11 Patienten konnte zeigen, dass die atypischen CD30-positiven Zellen einer Läsion einem Zellklon entstammen.…”

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“…Diese Untersuchung von 14 Hautbiopsaten von 11 Patienten konnte zeigen, dass die atypischen CD30-positiven Zellen einer Läsion einem Zellklon entstammen. Darüber hinaus lieû sich der identische CD30-positive Zellklon auch in anatomisch und zeitlich (bis zu 52 Monaten) unterschiedlichen Hautläsionen nachweisen [20]. Die untersuchten CD30-negativen Zellen zeigten sich in dieser Studie bis auf wenige Ausnahmen polyklonal und nicht dem CD30-positiven Zellklon zugehörig.…”

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Lymphomatoide Papulose - ein Schaf im Wolfspelz

Steinhoff¹

2004

Akt Dermatol

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ZusammenfassungBei der lymphomatoiden Papulose (LyP) handelt es sich um eine CD30-positive T-Zell-lymphoproliferative Erkrankung mit guter Prognose, aber häufig langjährigem, rezidivierendem Verlauf. Bei etwa 10 ± 20 % der Patienten mit LyP wird das Auftreten von malignen Lymphomen beobachtet. Aufgrund der Diskrepanz zwischen klinisch benignem Verlauf und malignem histologischen Zellbild wurde die Frage, ob es sich bei der LyP um eine reaktiv-entzündliche Erkrankung oder um ein niedrigmalignes kutanes T-Zell-Lymphom handelt, lange Zeit kontrovers diskutiert. Hinweise auf einen klonalen Ursprung der LyP erbrachten PCRUntersuchungen der T-Zell-Rezeptorumlagerung in Hautläsio-nen der LyP und assoziierter maligner Lymphome, die das Vorkommen eines identischen T-Zell-Klons in LyP als auch assoziiertem Lymphom zeigen konnten. Die Vermutung, dass es sich bei der LyP per se um eine monoklonale Erkrankung handelt, lieû sich kürzlich auf Einzelzellebene bestätigen. Dabei wurde gezeigt, dass sich der chronische Verlauf der LyP mit den für diese Erkrankung charakteristischen rezidivierenden, spontan abheilenden Hautläsionen auf die Expansion und Regression eines identischen T-Zell-Klons zurückführen lässt. Dementsprechend wird die LyP sowohl in der EORTC-als auch in der WHO-Klassifikation der Lymphome als niedrigmalignes T-Zell-Lymphom geführt, nimmt jedoch aufgrund des benignen Verlaufs mit einer 10-Jahres-Überlebensrate von 100 % eine Sonderstellung ein. AbstractLymphomatoid papulosis (LyP) represents a cutaneous CD30-positive T-cell lymphoproliferative disorder that takes a clinical benign course, often over a period of several years. From 10 ± 20 % of LyP cases are associated with malignant lymphoma. Due to the contrast of benign clinical course and malignant histological picture the nosological position of LyP was a long-standing enigma. On the one hand LyP was assigned to the group of benign reactive processes, on the other hand it was seen as a cutaneous lymphoma. By the finding of the same T-cell receptor rearrangements in the LyP as well as in the associated malignant lymphoma, LyP was identified as a precursor lesion. Recently single-cell analysis of T-cell receptor rearrangements in LyP cases being not associated with malignant lymphoma demonstrated that LyP unequivocally represents a monoclonal T-cell disorder. Moreover it was shown that the prolonged course of LyP with its typical features of waxing and waning is due to the expansion and regression of a single T-cell clone. According to these findings, nowadays LyP is included as a cutaneous low grade malignant lymphoma in both the EORTC-and WHO lymphoma classification. However due to its favourable 10-year survival rate of 100 %, LyP occupies an exceptional position in the spectrum of cutaneous lymphoma.

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Single-cell analysis of CD30+ cells in lymphomatoid papulosis demonstrates a common clonal T-cell origin

Cited by 78 publications

References 32 publications

Carcinoma-like vascular density in atypic keratoacanthoma suggests malignant progression

Carcinoma-like vascular density in atypic keratoacanthoma suggests malignant progression

Clonality testing of lymphoproliferative disorders in a large cohort of primary and consultant biopsies

Lymphomatoide Papulose - ein Schaf im Wolfspelz

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