{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T22:35:22Z","timestamp":1773009322065,"version":"3.50.1"},"reference-count":39,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,7,17]],"date-time":"2025-07-17T00:00:00Z","timestamp":1752710400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Reports"],"abstract":"<jats:p>Background and Clinical Significance: Neurofibromatosis type 1 (NF1) predisposes individuals to various peripheral nerve sheath tumors (PNSTs), including benign neurofibromas, malignant peripheral nerve sheath tumors (MPNSTs), and intermediate lesions known as atypical neurofibromatous neoplasms of uncertain biologic potential (ANNUBP), previously often termed atypical neurofibroma. These atypical lesions are considered premalignant precursors to MPNST. Case Presentation: We present the case of a 33-year-old male with NF1 who developed a rapidly growing, painful mass in his right calf. Clinical examination revealed signs consistent with NF1. Magnetic resonance imaging showed a large, heterogeneous mass in the lateral compartment. Biopsy revealed a neurofibroma with hypercellularity, moderate atypia, scarce S100 positivity, focal CD34 positivity, and an elevated Ki-67 proliferation index of 10\u201312%, consistent with ANNUBP. The patient underwent wide surgical resection, including the fibula and peroneal muscles. At the 30-month follow-up, there was no local recurrence, though the patient had a mild residual limp. Discussion: This case highlights the clinical presentation, diagnostic features, and management considerations for ANNUBP in NF1, emphasizing the importance of recognizing warning signs and the role of pathology in guiding treatment for these high-risk precursor lesions.<\/jats:p>","DOI":"10.3390\/reports8030112","type":"journal-article","created":{"date-parts":[[2025,7,17]],"date-time":"2025-07-17T10:33:47Z","timestamp":1752748427000},"page":"112","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Giant Atypical Neurofibroma of the Calf in Neurofibromatosis Type 1: Case Report and Literature Review"],"prefix":"10.3390","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4774-6507","authenticated-orcid":false,"given":"Lyubomir","family":"Gaydarski","sequence":"first","affiliation":[{"name":"Department of Anatomy, Histology and Embryology, Medical University of Sofia, 1431 Sofia, Bulgaria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8343-0337","authenticated-orcid":false,"given":"Georgi P.","family":"Georgiev","sequence":"additional","affiliation":[{"name":"Department of Orthopedics and Traumatology, University Hospital Queen Giovanna-ISUL, Medical University of Sofia, 1431 Sofia, Bulgaria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4280-0017","authenticated-orcid":false,"given":"Svetoslav A.","family":"Slavchev","sequence":"additional","affiliation":[{"name":"University Hospital of Orthopedics \u201cProf. B. Boychev\u201d, Medical University of Sofia, 1413 Sofia, Bulgaria"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1485","DOI":"10.4103\/jcrt.jcrt_1742_21","article-title":"Honokiol: Treatment for Malignant Peripheral Nerve Sheath Tumors","volume":"19","author":"Joshi","year":"2023","journal-title":"J. Cancer Res. Ther."},{"key":"ref_2","unstructured":"Adil, A., Koritala, T., Munakomi, S., and Singh, A.K. (2025, May 20). Neurofibromatosis Type 1, Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK459358\/."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1016\/S1474-4422(14)70063-8","article-title":"Neurofibromatosis Type 1: A Multidisciplinary Approach to Care","volume":"13","author":"Hirbe","year":"2014","journal-title":"Lancet Neurol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2405","DOI":"10.1038\/s41388-022-02290-1","article-title":"Malignant Peripheral Nerve Sheath Tumor: Models, Biology, and Translation","volume":"41","author":"Somatilaka","year":"2022","journal-title":"Oncogene"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1430","DOI":"10.1056\/NEJMoa1912735","article-title":"Selumetinib in Children with Inoperable Plexiform Neurofibromas","volume":"382","author":"Gross","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_6","first-page":"282","article-title":"Tumors of the Peripheral Nervous System","volume":"33","author":"Ariel","year":"1983","journal-title":"CA Cancer J. Clin."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Bernthal, N.M., Jones, K.B., Monument, M.J., Liu, T., Viskochil, D., and Randall, R.L. (2013). Lost in Translation: Ambiguity in Nerve Sheath Tumor Nomenclature and Its Resultant Treatment Effect. Cancers, 5.","DOI":"10.3390\/cancers5020519"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.humpath.2017.05.010","article-title":"Histopathologic Evaluation of Atypical Neurofibromatous Tumors and Their Transformation into Malignant Peripheral Nerve Sheath Tumor in Patients with Neurofibromatosis 1\u2014A Consensus Overview","volume":"67","author":"Miettinen","year":"2017","journal-title":"Hum. Pathol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"818","DOI":"10.1093\/neuonc\/noy013","article-title":"The Characteristics of 76 Atypical Neurofibromas as Precursors to Neurofibromatosis 1 Associated Malignant Peripheral Nerve Sheath Tumors","volume":"20","author":"Higham","year":"2018","journal-title":"Neuro-Oncology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.21873\/anticanres.15592","article-title":"Peripheral Nerve Sheath Tumors in Patients with Neurofibromatosis Type 1: Morphological and Immunohistochemical Study","volume":"42","author":"Friedrich","year":"2022","journal-title":"Anticancer Res."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Picci, P., Manfrini, M., Fabbri, N., Gambarotti, M., and Vanel, D. (2014). Malignant Schwannoma: Malignant Peripheral Nerve Sheath Tumor. Atlas of Musculoskeletal Tumors and Tumorlike Lesions: The Rizzoli Case Archive, Springer International Publishing.","DOI":"10.1007\/978-3-319-01748-8"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1002\/gcc.20921","article-title":"Atypical Neurofibromas in Neurofibromatosis Type 1 Are Premalignant Tumors","volume":"50","author":"Beert","year":"2011","journal-title":"Genes Chromosomes Cancer"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1002\/jso.23736","article-title":"The Effect of Surgical Margins on Outcomes for Low Grade MPNSTs and Atypical Neurofibroma","volume":"110","author":"Bernthal","year":"2014","journal-title":"J. Surg. Oncol."},{"key":"ref_14","unstructured":"WHO Classification of Tumours Editorial Board (2020). Neurofibroma. Soft Tissue and Bone Tumours, International Agency for Research on Cancer. [5th ed.]. Available online: https:\/\/publications.iarc.fr\/588."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Gr\u00fcbel, N., Antoniadis, G., K\u00f6nig, R., Wirtz, C.R., Bremer, J., Pala, A., Reuter, M., and Pedro, M.T. (2024). Case Report: Atypical Neurofibromatous Neoplasm with Uncertain Biological Potential of the Sciatic Nerve and a Widespread Arteriovenous Fistula Mimicking a Malignant Peripheral Nerve Tumor in a Young Patient with Neurofibromatosis Type 1. Front. Oncol., 14.","DOI":"10.3389\/fonc.2024.1391456"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"77","DOI":"10.25259\/SNI-76-2019","article-title":"Giant Dumbbell C2C3 Neurofibroma Invading Prebulbar Cistern: Case Report and Literature Review","volume":"10","author":"Serrano","year":"2019","journal-title":"Surg. Neurol. Int."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"00368504211004269","DOI":"10.1177\/00368504211004269","article-title":"A Solitary Giant Neurofibroma of Inguinal Region: A Case Report","volume":"104","author":"Zhou","year":"2021","journal-title":"Sci. Prog."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e04152","DOI":"10.1002\/ccr3.4152","article-title":"A 63-kg Giant Neurofibroma in the Right Lower Extremity and Gluteal Region of a 22-Year-Old Woman: A Case Report","volume":"9","author":"Sharma","year":"2021","journal-title":"Clin. Case Rep."},{"key":"ref_19","first-page":"987623","article-title":"Multidisciplinary Management of a Giant Plexiform Neurofibroma by Double Sequential Preoperative Embolization and Surgical Resection","volume":"2013","author":"Barastegui","year":"2013","journal-title":"Case Rep. Neurol. Med."},{"key":"ref_20","first-page":"e66190","article-title":"A Rare Case of Sural Schwannoma with Involvement of the Medial Sural Cutaneous Nerve: A Case Report and Literature Review","volume":"16","author":"Petrova","year":"2024","journal-title":"Cureus"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1016\/j.soc.2016.05.009","article-title":"Malignant Peripheral Nerve Sheath Tumor","volume":"25","author":"James","year":"2016","journal-title":"Surg. Oncol. Clin. N. Am."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1148\/radiol.2241011113","article-title":"Imaging of Fatty Tumors: Distinction of Lipoma and Well-Differentiated Liposarcoma","volume":"224","author":"Kransdorf","year":"2002","journal-title":"Radiology"},{"key":"ref_23","unstructured":"Weir, C.B., and St Hilaire, N.J. (2025, May 20). Epidermal Inclusion Cyst, Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK532310\/."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"54","DOI":"10.3390\/dermatopathology10010008","article-title":"Rare Variants of Dermatofibrosarcoma Protuberans: Clinical, Histologic, and Molecular Features and Diagnostic Pitfalls","volume":"10","author":"Trinidad","year":"2023","journal-title":"Dermatopathology"},{"key":"ref_25","first-page":"154","article-title":"Endobronchial Neurogenic Tumor: A Combination of Traumatic Neuroma and Neurofibroma","volume":"20","author":"Tandon","year":"2017","journal-title":"Respir. Med. Case Rep."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1634\/theoncologist.2010-0281","article-title":"Desmoid Tumors: Clinical Features and Treatment Options for Advanced Disease","volume":"16","author":"Kasper","year":"2011","journal-title":"Oncologist"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"810","DOI":"10.5858\/arpa.2011-0335-OA","article-title":"Differentiating Neurotized Melanocytic Nevi from Neurofibromas Using Melan-A (MART-1) Immunohistochemical Stain","volume":"136","author":"Chen","year":"2012","journal-title":"Arch. Pathol. Lab. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"217","DOI":"10.5858\/arpa.2011-0056-RS","article-title":"Aggressive Angiomyxoma","volume":"136","author":"Sutton","year":"2012","journal-title":"Arch. Pathol. Lab. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"195","DOI":"10.2214\/AJR.10.5734","article-title":"CT and MRI Evaluation of Nerve Sheath Tumors of the Cervical Vagus Nerve","volume":"197","author":"Anil","year":"2011","journal-title":"AJR Am. J. Roentgenol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1055\/s-0035-1546823","article-title":"Advanced MR Imaging of Peripheral Nerve Sheath Tumors Including Diffusion Imaging","volume":"19","author":"Soldatos","year":"2015","journal-title":"Semin. Musculoskelet. Radiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"vdae021","DOI":"10.1093\/noajnl\/vdae021","article-title":"Discrimination of Benign, Atypical, and Malignant Peripheral Nerve Sheath Tumors in Neurofibromatosis Type 1 Using Diffusion-Weighted MRI","volume":"6","author":"Ristow","year":"2024","journal-title":"Neuro-Oncol. Adv."},{"key":"ref_32","unstructured":"Messersmith, L., and Krauland, K. (2025, May 20). Neurofibroma, Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK539707\/."},{"key":"ref_33","first-page":"30","article-title":"Use of Calretinin, CD56, and CD34 for Differential Diagnosis of Schwannoma and Neurofibroma","volume":"45","author":"Park","year":"2011","journal-title":"J. Pathol. Transl. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1148\/rg.210235","article-title":"Neurofibromatosis from Head to Toe: What the Radiologist Needs to Know","volume":"42","author":"Wang","year":"2022","journal-title":"Radiographics"},{"key":"ref_35","unstructured":"Charifa, A., Azmat, C.E., and Badri, T. (2025, May 20). Lipoma Pathology, Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK482343\/."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/j.ejro.2019.08.003","article-title":"Overview of Epidermoid Cyst","volume":"6","author":"Trinh","year":"2019","journal-title":"Eur. J. Radiol. Open"},{"key":"ref_37","unstructured":"Neelon, D., Lannan, F., and Childs, J. (2025, May 20). Granular Cell Tumor, Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK563150\/."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"374","DOI":"10.2214\/AJR.14.12888","article-title":"Myxoid Soft-Tissue Neoplasms: Comprehensive Update of the Taxonomy and MRI Features","volume":"204","author":"Baheti","year":"2015","journal-title":"AJR Am. J. Roentgenol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"djx124","DOI":"10.1093\/jnci\/djx124","article-title":"Neurofibromatosis Type 1-Associated MPNST State of the Science: Outlining a Research Agenda for the Future","volume":"109","author":"Reilly","year":"2017","journal-title":"J. Natl. Cancer Inst."}],"container-title":["Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2571-841X\/8\/3\/112\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:11:07Z","timestamp":1760033467000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2571-841X\/8\/3\/112"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,17]]},"references-count":39,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2025,9]]}},"alternative-id":["reports8030112"],"URL":"https:\/\/doi.org\/10.3390\/reports8030112","relation":{},"ISSN":["2571-841X"],"issn-type":[{"value":"2571-841X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,17]]}}}