bims-netuvo 2023-08-27 papers

bims-netuvo

Biomed News

on Nerves in tumours of visceral organs

Issue of 2023–08–27
seven papers selected by
Maksym V. Kopanitsa, The Francis Crick Institute

Perineural invasion detection in pancreatic ductal adenocarcinoma using artificial intelligence.
Phenotype screens of murine pancreatic cancer identify a Tgfa-Ccl2-paxillin axis driving human-like neural invasion.
Neoadjuvant radiation to facilitate surgical treatment of a microcystic adnexal carcinoma with perineural invasion of the vulvar region.
Transperineal excision of malignant peripheral nerve sheath tumors of the ischiorectal fossa: Case report of a rare tumor in a frequently forgotten anatomical region.
Peripheral Schwannoma Presenting as a Retro-Malleolar Mass: A Case Report.
Diagnostic conundrums of schwannomas: two cases highlighting morphological extremes and diagnostic challenges in biopsy specimens of soft tissue tumors.
The Contribution of Oxidative Stress to NF1-Altered Tumors.

Sci Rep. 2023 Aug 21. 13(1): 13628

Perineural invasion detection in pancreatic ductal adenocarcinoma using artificial intelligence.

Sarah Borsekofsky, Shlomo Tsuriel, Rami R Hagege, Dov Hershkovitz.

Perineural invasion (PNI) refers to the presence of cancer cells around or within nerves, raising the risk of residual tumor. Linked to worse prognosis in pancreatic ductal adenocarcinoma (PDAC), PNI is also being explored as a therapeutic target. The purpose of this work was to build a PNI detection algorithm to enhance accuracy and efficiency in identifying PNI in PDAC specimens. Training used 260 manually segmented nerve and tumor HD images from 6 scanned PDAC cases; Analytical performance analysis used 168 additional images; clinical analysis used 59 PDAC cases. The algorithm pinpointed key areas of tumor-nerve proximity for pathologist confirmation. Analytical performance reached sensitivity of 88% and 54%, and specificity of 78% and 85% for the detection of nerve and tumor, respectively. Incorporating tumor-nerve distance in clinical evaluation raised PNI detection from 52 to 81% of all cases. Interestingly, pathologist analysis required an average of only 24 s per case. This time-efficient tool accurately identifies PNI in PDAC, even with a small training cohort, by imitating pathologist thought processes.

DOI: https://doi.org/10.1038/s41598-023-40833-y
J Clin Invest. 2023 Aug 22. pii: e166333. [Epub ahead of print]

Phenotype screens of murine pancreatic cancer identify a Tgfa-Ccl2-paxillin axis driving human-like neural invasion.

Xiaobo Wang, Rouzanna Istvanffy, Linhan Ye, Steffen Teller, Melanie Laschinger, Kalliope N Diakopoulos, Kıvanç Görgülü, Qiaolin Li, Lei Ren, Carsten Jäger, Katja Steiger, Alexander Muckenhuber, Baiba Vilne, Kaan Çifcibaşı, Carmen Mota Reyes, Ümmügülsüm Yurteri, Maximilian Kießler, Ibrahim H Gürçınar, Maya M Sugden, Saliha Elif Yıldızhan, Osman Ugur Sezerman, Sümeyye Çilingir, Güldal Süyen, Maximilian Reichert, Roland M Schmid, Stefanie Bärthel, Rupert Öllinger, Achim Krüger, Roland Rad, Dieter Saur, Hana Algül, Helmut Friess, Marina Lesina, Güralp Onur Ceyhan, Ihsan Ekin Demir.

  Solid cancers like pancreatic cancer (PDAC) frequently exploit nerves for rapid dissemination. This neural invasion (NI) is an independent prognostic factor in PDAC, but insufficiently modelled in genetically-engineered mouse models (GEMM) of PDAC. Here, we systematically screened for human-like NI in Europe's largest repository of GEMM of PDAC comprising 295 different genotypes. This phenotype screen uncovered two GEMM of PDAC with human-like NI, which are both characterized by pancreas-specific overexpression of transforming-growth-factor-alpha (TGFa) and conditional depletion of p53. Mechanistically, cancer-cell-derived TGFa upregulated CCL2 secretion from sensory neurons, which induced hyperphosphorylation of the cytoskeletal protein paxillin via CCR4 on cancer cells. This activated the cancer migration machinery and filopodia formation toward neurons. Disrupting CCR4 or paxillin activity limited NI, and dampened tumor size and tumor innervation. In human PDAC, phospho-paxillin and TGFa-expression constituted strong prognostic factors. Therefore, TGFa-CCL2-CCR4-p-paxillin axis is a clinically actionable target for constraining NI and tumor progression in PDAC.

Keywords:  Cancer; Innervation; Oncology

DOI:  https://doi.org/10.1172/JCI166333
JAAD Case Rep. 2023 Aug;38 72-74

Neoadjuvant radiation to facilitate surgical treatment of a microcystic adnexal carcinoma with perineural invasion of the vulvar region.

William J Nahm, Stanley Chen, Saiyan Joseph, Paul Chu, Jane Yoo.



Keywords:  microcystic adnexal carcinoma; neoadjuvant radiation; tissue conservation; treatment strategy; vulvar carcinoma

DOI:  https://doi.org/10.1016/j.jdcr.2023.06.008
Int J Surg Case Rep. 2023 Aug 18. pii: S2210-2612(23)00803-9. [Epub ahead of print]110 108674

Transperineal excision of malignant peripheral nerve sheath tumors of the ischiorectal fossa: Case report of a rare tumor in a frequently forgotten anatomical region.

Chiara Eberspacher, Stefano Arcieri, Enrico Coletta, Stefano Pontone, Francesco Leone Arcieri, Domenico Mascagni.

   INTRODUCTION AND IMPORTANCE: Malignant peripheral nerve sheath tumor is an aggressive tumor that arises from peripheral nerves. Frequently associated with neurofibromatosis, its common localization is in the extremities, trunk (with paravertebral regions), neck and head. Some cases have been found in the pelvis or uterus. In this case report we illustrate one of the rarest localization of this type of tumor in the ischiorectal fossa, with the full recovery of the patient after surgical excision and radiotherapy.
CASE PRESENTATION: A 61-year-old woman showed a lump near the anus which was initially diagnosed as a lipoma of the right ischiorectal fossa, by Computed Tomography scan. The tumor was completely removed with a minimal skin incision, and the patient had a complete recovery. Only the pathological examination determined the diagnosis of malignant peripheral nerve sheath tumor, in this unusual localization. In consideration of its high aggressiveness the patient underwent radiotherapy. After more than two years of follow-up there is no sign of recurrence.
DISCUSSION: In sites far from branches of nerves, malignant peripheral nerve sheath tumors can be considered episodic. Ischiorectal fossa is a rare localization, and the differential diagnosis from benign mesenchymal cell tumors can be challenging. When possible, a biopsy should be performed before surgery.
CONCLUSION: Surgical excision of tumors in ischiorectal fossa should be always complete, in consideration of possible histological surprise.

Keywords:  Case report; Histological surprise; Ischiorectal fossa tumor; Malignant peripheral nerve sheath tumors

DOI:  https://doi.org/10.1016/j.ijscr.2023.108674
Cureus. 2023 Jul;15(7): e42137

Peripheral Schwannoma Presenting as a Retro-Malleolar Mass: A Case Report.

Lokeshwar Raaju Addi Palle, Venu Gopal Reddy Depa, Krushi Shah, Cuauhtemoc Jeffrey Soto, Bitania A Aychilluhim, Vipul V Rakhunde.

  Schwannomas are rare peripheral nerve tumors that can present with diverse clinical manifestations. They commonly present as solitary, encapsulated masses and can occur in various locations throughout the body. This case report presents a comprehensive analysis of a peripheral schwannoma in a 29-year-old male patient who presented with numbness, pain, and paresthesias on the plantar aspect of the left foot. The symptoms progressively worsened, impacting the patient's daily activities. Physical examination revealed tenderness on the medial aspect of the left foot, along with prolonged episodes of paresthesia and recurrent numbness. Imaging studies confirmed the presence of a retro-malleolar mass, consistent with a peripheral schwannoma. The patient underwent successful surgical excision of the mass, resulting in complete resolution of symptoms. This case emphasizes the importance of considering peripheral schwannomas in the differential diagnosis of patients presenting with foot symptoms and highlights the effectiveness of surgical excision as a treatment modality for these tumors.

Keywords:  case report; differential diagnosis; numbness; pain; paresthesias; peripheral schwannoma; plantar foot; surgical excision; treatment

DOI:  https://doi.org/10.7759/cureus.42137
J Pathol Transl Med. 2023 Aug 24.

Diagnostic conundrums of schwannomas: two cases highlighting morphological extremes and diagnostic challenges in biopsy specimens of soft tissue tumors.

Chankyung Kim, Yang-Guk Chung, Chan Kwon Jung.

  Schwannomas are benign, slow-growing peripheral nerve sheath tumors commonly occurring in the head, neck, and flexor regions of the extremities. Although most schwannomas are easily diagnosable, their variable morphology can occasionally create difficulty in diagnosis. Reporting pathologists should be aware that schwannomas can exhibit a broad spectrum of morphological patterns. Clinical and radiological examinations can show correlation and should be performed, in conjunction with ancillary tests, when appropriate. Furthermore, deferring a definitive diagnosis until excision may be necessary for small biopsy specimens and frozen sections. This report underscores these challenges through examination of two unique schwannoma cases, one predominantly cellular and the other myxoid, both of which posed significant challenges in histological interpretation.

Keywords:  Biopsy; Extremities; Frozen sections; Immunohistochemistry; Neurilemmoma; Pathologists; Soft tissue neoplasms

DOI:  https://doi.org/10.4132/jptm.2023.07.13
Antioxidants (Basel). 2023 Aug 04. pii: 1557. [Epub ahead of print]12(8):

The Contribution of Oxidative Stress to NF1-Altered Tumors.

Elisabetta Kuhn, Federica Natacci, Massimo Corbo, Luigi Pisani, Stefano Ferrero, Gaetano Bulfamante, Donatella Gambini.

  The neurofibromatosis-1 gene (NF1) was initially characterized because its germline mutation is responsible for an inherited syndromic disease predisposing tumor development, in particular neurofibromas but also various malignancies. Recently, large-scale tumor sequencing efforts have demonstrated NF1 as one of the most frequently mutated genes in human cancer, being mutated in approximately 5-10% of all tumors, especially in malignant peripheral nerve sheath tumors and different skin tumors. NF1 acts as a tumor suppressor gene that encodes neurofibromin, a large protein that controls neoplastic transformation through several molecular mechanisms. On the other hand, neurofibromin loss due to NF1 biallelic inactivation induces tumorigenic hyperactivation of Ras and mTOR signaling pathways. Moreover, neurofibromin controls actin cytoskeleton structure and the metaphase-anaphase transition. Consequently, neurofibromin deficiency favors cell mobility and proliferation as well as chromosomal instability and aneuploidy, respectively. Growing evidence supports the role of oxidative stress in NF1-related tumorigenesis. Neurofibromin loss induces oxidative stress both directly and through Ras and mTOR signaling activation. Notably, innovative therapeutic approaches explore drug combinations that further increase reactive oxygen species to boost the oxidative unbalance of NF1-altered cancer cells. In our paper, we review NF1-related tumors and their pathogenesis, highlighting the twofold contribution of oxidative stress, both tumorigenic and therapeutic.

Keywords:  NF1; ROS; neurofibromatosis; neurofibromin; oxidative stress; pathogenesis; therapy

DOI:  https://doi.org/10.3390/antiox12081557