Clinical, Morphological and Molecular Features of Spitz tumors

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Klinické, morfologické a molekulární vlastnosti Spitzoidních nádorů

Spitzoidní nádory představují heterogenní skupinu melanocytárních neoplázií vykazujících široké spektrum biologického chování od zcela benigních afekcí typu névu Spitzové až po maligní léze v podobě spitzoidních melanomů. Mezi těmito dvěma skupinami se pak nacházejí léze s nejistým biologickým chováním v podobě atypických spitzoidních tumorů. Histologicky jsou charakterizované objemnými epiteloidními a/nebo vřetenitými melanocyty uspořádanými do fasciklů nebo hnízd a často s charakteristickou epidermální hyperplázií a fibrovaskulárními stromálními změnami v okolí.

Rozpoznání specifických strukturálních přestaveb v genech pro tyrozinkinázové receptory ROS1, ALK, NTRK1, NTRK2, NTRK3, RET, MET, serin threoninové kinázy BRAF a MAP3K8 či HRAS mutací v posledním desetiletí umožnilo přesnější klinickou, morfologickou a molekulární subklasifikaci spitzoidních tumorů. Rozpoznání specifických histologických rysů pak může dermatopatologům napomoct nejen v hodnocení těchto lézí, ale může i nepřímo poukazovat na konkrétní molekulární změny.

Tento doškolovací článek se zaměřuje na klinické a morfologické nálezy u molekulárně definovaných podskupin spitzoidních tumorů.

Klíčová slova:

ALK – Spitzoidní tumor – atypický spitzoidní tumor – spitzoidní melanom – molekulární změna – molekulárně-morfologická korelace – ROS1 – NTRK1 – NTRK2 – NTRK3 – RET – MET – BRAF – MAP3K8 fúze – HRAS mutace – MAP2K1 mutace

Authors: Michele Donati ^1,2; Boulos Mansour ³; Michael Hagstrom ⁴; Pedram Gerami ⁴; Dmitry V. Kazakov ⁵
Authors place of work: Department of Pathology, Fondazione Policlinico Universitario Campus Bio-Medico, Rome, Italy ¹; University Campus Bio-Medico of Rome, Rome, Italy ²; Department of Pathology, Ospedale Israelitico di Roma, Italy ³; Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA. ⁴; IDP Institut für Dermatohistopathologie, Pathologie Institut Enge, Zürich, Switzerland ⁵
Published in the journal: Čes.-slov. Patol., 60, 2024, No. 1, p. 35-48
Category: Přehledový článek

Summary

Spitz tumors represent a heterogeneous group of challenging melanocytic neoplasms, displaying a range of biological behaviors, spanning from benign lesions, Spitz nevi (SN) to Spitz melanomas (SM), with intermediate lesions in between known as atypical Spitz tumors (AST). They are histologically characterized by large epithelioid and/or spindled melanocytes arranged in fascicles or nests, often associated with characteristic epidermal hyperplasia and fibrovascular stromal changes. In the last decade, the detection of mutually exclusive structural rearrangements involving receptor tyrosine kinases ROS1, ALK, NTRK1, NTRK2, NTRK3, RET, MET, serine threonine kinases BRAF and MAP3K8, or HRAS mutation, led to a clinical, morphological and molecular based classification of Spitz tumors.

The recognition of some reproducible histological features can help dermatopathologist in assessing these lesions and can provide clues to predict the underlying molecular driver.

In this review, we will focus on clinical and morphological findings in molecular Spitz tumor subgroups.

Keywords:

classification – histopathology – melanocytic lesions – genetic alterations – dermoscopy-histopathology correlations – intermediate lesions – melanocytomas – practical recommendations for diagnosis – ALK – Spitz tumor – Atypical Spitz tumor – Spitz melanoma – molecular driver – molecular morphological correlation – ROS1 – NTRK1 – NTRK2 – NTRK3 – RET – MET – BRAF –MAP3K8 fusion – HRAS mutation – MAP2K1 mutation

Zdroje

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