Background
Peripheral and deep en face margin assessment (PDEMA) is associated with the highest reported cure rates for many cutaneous malignancies. PDEMA encompasses both Mohs micrographic surgery (Mohs) and Tubingen methods and has been incorporated into the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for nonmelanoma skin cancers (NMSCs) for many years. The Tubingen torte and muffin techniques afford complete histologic visualization of peripheral and deep marginal surfaces using the same mapping and precise re-excision as Mohs. The methods differ in that Tubingen histologic margins are interpreted by a pathologist usually within 1 to 5 days, whereas Mohs margins are processed via rapid frozen sections within an hour and are interpreted by the surgeon who has training in histologic identification of positive margins. Studies have shown Mohs to be superior to vertical sections in randomized controlled trials of basal cell carcinoma (BCC),1,2 cohort studies and systematic reviews of cutaneous squamous cell carcinoma (cSCC),3–7 a systematic review of dermatofibrosarcoma protuberans (DFSP),8 and a cohort study of extramammary Paget disease (EMPD).9 Tubingen methods have been shown to have similarly high cure rates in retrospective cohort studies of DFSP and a systematic review of cSCC with perineural invasion.6,10–13 Table 1 provides a summary of data.2,6,8,14 The high cure rates are thought to be due to PDEMA’s complete histologic visualization of peripheral and deep marginal surfaces, and careful mapping and re-excision of regions of residual tumor to ensure complete eradication of the tumor.6,15 Techniques utilizing en face peripheral margin evaluation but vertical sectioning of the deep margin do not constitute PDEMA.16
Outcome Comparison by Margin Assessment Method: PDEMA Versus Vertical Sections
In 2021, NCCN designated PDEMA (then termed complete circumferential peripheral and deep margin assessment [CCPDMA]) as the preferred treatment for DFSP17 and for very-high-risk cSCC with any of the following features: 4-cm clinical preoperative diameter, poor differentiation, invasion beyond subcutaneous fat or >6 mm in vertical measurement, desmoplastic SCC, lymphatic invasion, vascular invasion, or invasion of nerves deep to the dermis or ≥0.1 mm in caliber.18 In 2023, high-risk BCC was added to the list for which PDEMA is the preferred treatment. High-risk BCC is defined as BCCs that are either recurrent, are ≥1 cm and are in the H zone (which refers to the “mask areas” of the face, including the central face, eyelids, eyebrows, periorbital, nose, lips, chin, mandible, preauricular and postauricular skin, temple, and ear), or have an aggressive histologic subtype.1,2,19
The term “en face” (on the face) is used by pathologists to describe when the specimen is cut parallel or nearly parallel to the marginal surfaces, not perpendicularly as in standard histologic vertical sections. In 2022, the CCPDMA term was changed to PDEMA to specify that it is the en face tissue sectioning of margins, including the deep margin, which allows for histologic visualization of the entire marginal surface as opposed to vertical (“bread loafed”) sections. Vertical sections only allow a small fraction of the marginal surface to be evaluated, resulting in some imprecision in detecting tumor at the margins, which can result in false-negative margins20 (Figure 1).
Vertical sectioning of tumor excision specimens. Thin tissue sections (shown in blue) are removed from the specimen, generally at 2- to 5-mm intervals across the specimen, placed on glass slides, stained, and evaluated by a pathologist for the presence or absence of tumor at the marginal edge. The regions between the thin sections are not analyzed, which results in a large proportion of the surface area not being visualized by the pathologist. Thin tendrils of tumor (shown in pink) at the margin are therefore not visualized, thus generating a false-negative pathology report.
Citation: Journal of the National Comprehensive Cancer Network 22, 9; 10.6004/jnccn.2024.7037
The Tubingen methods of PDEMA (Tubingen torte and muffin techniques; Figure 2) were developed in Germany.11,12,21 Tubingen PDEMA is the same as Mohs except that (1) a pathologist determines where tumor remains at the margin and precisely relays this information to the resecting surgeon, and (2) marginal tissues are usually cut not from frozen tissue blocks, but rather from formalin-fixed, paraffin-embedded (FFPE) tissue blocks within 12 to 36 hours. It is possible for Tubingen PDEMA tissue blocks to be processed in surgical pathology laboratories via rapid frozen sections as is done in Mohs. In such cases, high-quality frozen sections must be produced that visualize the entire marginal surface with minimal artifact and missing areas, which can lead to prolonged general anesthesia. Therefore, most Tubingen PDEMA is performed via paraffin sections. Although it is generally advisable to delay reconstruction until margins are known to be clear, wounds may be closed primarily or partially, or managed by temporizing dressings (eg, Integra, bolsters, vacuum-assisted closure [VAC] dressings) without significant undermining or other disruption of tissue planes (eg, flaps) to stabilize the wound while awaiting the margin status, particularly if this can avoid hospitalization.
(A) Tubingen muffin schematic. The Tubingen muffin technique lays out the entire marginal surface like the wrapper of a muffin or cupcake. The marginal surface is placed as a single tissue block onto a 2-cm glass slide and is thus appropriate for small tumors. (B) Tubingen torte schematic. The Tubingen torte technique visualizes the entire marginal surface of larger tumors by dividing the marginal tissue into multiple tissue blocks, placing the marginal surface of each on a different glass slide.
Citation: Journal of the National Comprehensive Cancer Network 22, 9; 10.6004/jnccn.2024.7037
A survey distributed to the NCCN Skin Cancers Excluding Melanoma Panel members and physicians participating in keratinocyte carcinoma (BCC and cSCC) treatment at NCCN Member Institutions revealed that Tubingen PDEMA was poorly understood. Perceived barriers to implementation included “deference to pathologists to determine the appropriate method for margin assessment” and “logistical difficulty” including management of open wounds while awaiting margin interpretation.22 A recent single-institution survey within the divisions of dermatology and otolaryngology at the University of Wisconsin-Madison identified distinct knowledge gaps surrounding the understanding and utilization of PDEMA.23 Although many surgeons and pathologists agree on the value of PDEMA, there is a lack of clarity regarding what qualifies as non-Mohs PDEMA per the NCCN’s definition. To ensure correct implementation and execution of PDEMA, the key components of PDEMA that allow for complete margin visualization and accurate serial excision are detailed herein with the hope of achieving greater adherence to NCCN Guidelines regarding PDEMA.
Components of PDEMA
The techniques that currently meet criteria for PDEMA include Mohs developed by Drs. Frederic Mohs, Theodore Tromovitch, and Samuel Stegman in the United States,15,24 and the Tubingen torte and muffin techniques developed by Dr. Helmut Breuninger in Tubingen, Germany.11,12,21,25,26 Tubingen PDEMA requires clear communication between the resecting surgeon and the pathologist or dermatopathologist. Both parties must understand the orientation of all marginal tissue blocks relative to each other and to the wound bed.
In Mohs, the tumor is generally debulked or curetted to remove all gross disease, and then a layer of grossly normal marginal tissue is removed. PDEMA assessment is then performed on the marginal specimen(s). The debulking of gross tumor helps to ensure the deep margin will be adequate, in addition to preoperative imaging in some cases. Surgical oncologists and general surgeons are trained to use en bloc resection aided by preoperative imaging to determine the width and depth of the tissue specimen removed. The en bloc specimen includes a prescribed additional margin of tissue that appears clinically and/or radiologically normal. Although excising a separate marginal specimen can help to facilitate orientation due to more precise block division points connoted on the specimen and wound bed, surgical oncologists and general surgeons may be reluctant to debulk tumors because en bloc resection principles discourage cutting intentionally close to the tumor due to concern for spreading the tumor intraoperatively. A <1% risk of spread has been reported for several cancers, including prostate cancer27 and noncutaneous sarcomas,28–31 via needle tracks from fine needle aspiration (FNA) or core biopsies. There is no report of needle track or intraoperative spread of cSCC, BCC, or DFSP, except for one case report of needle track cSCC identified at the FNA biopsy site through percutaneous biopsy of submandibular lymph nodes positive for metastatic cSCC.32 Debulking of clinical tumor is therefore safe for cSCC, BCC, and DFSP, and surgeons may choose whether to perform en bloc resection or to debulk gross tumor and then excise a separate marginal specimen. Processes to accomplish Tubingen PDEMA are detailed later in the “Protocol for Tubingen PDEMA” section.
Barriers to and Indications for Tubingen PDEMA Relative to Mohs
PDEMA wounds are definitively reconstructed after clear margins are achieved, which is generally determined within 1 to 5 days for Tubingen PDEMA. Mohs is most commonly used in the United States to achieve PDEMA33,34 because clear margins are achieved and the wound is reconstructed usually in a single day. In many other countries, there are significant barriers to Mohs, including financial incentives for inpatient care, lack of pathology and surgical training during dermatology residency, lack of fellowship training opportunities to build upon the former, and prohibition of nonpathologists determining margin status, regardless of training. Finally, reimbursement mechanisms for Mohs have not been established in many countries, making it financially difficult for trained Mohs surgeons to incur the costs of frozen section histology laboratories. Subsequently, Tubingen PDEMA is performed in many countries despite the longer time generally needed to evaluate the marginal tissues.
Tubingen PDEMA may be considered in the United States, particularly if the Mohs surgeon does not have operating room access and the patient may have difficulty tolerating the procedure under local anesthesia despite oral sedation or anxiolytics (such as pediatric patients). Excisions of extensive tumors can be performed by multidisciplinary teams where resection is initiated with Mohs and completed via Tubingen PDEMA. The Mohs surgeon denotes areas of the wound bed that remain positive and relays this information to the next surgeon (eg, via marked photographs, sutures, verbally) so that additional resection is undertaken in those regions. Tubingen PDEMA techniques are then used to evaluate the tissue resected by the second surgeon (except for bone and nerve resections for which en face processing is sometimes not feasible). Benefits of doing Mohs instead of or prior to Tubingen in extensive tumors include (1) same day pathology and (2) limiting anesthesia time.
Protocol for Tubingen PDEMA
To achieve higher adherence with NCCN Guidelines for PDEMA for skin cancer resection, herein we provide a protocol for Tubingen PDEMA detailing processing and transfer of specimens to pathology and proper communication between surgeon and pathologist. Modified protocols can be developed, so long as they meet the basic requirements of PDEMA (see “Additional Considerations” section). A case of NCCN very-high-risk cSCC on the mid back is presented (Figure 3) to illustrate in a stepwise fashion how Tubingen PDEMA is performed. The critical steps that are required for Tubingen PDEMA are as follows:
(A, B) Preoperative appearance of a recurrent cutaneous squamous cell carcinoma meeting multiple NCCN very-high-stage criteria (≥4 cm, poorly differentiated) for which PDEMA is the NCCN-preferred treatment.
Abbreviation: PDEMA, peripheral and deep en face margin assessment.
Citation: Journal of the National Comprehensive Cancer Network 22, 9; 10.6004/jnccn.2024.7037
Step 1
The tumor is removed as either a single en bloc specimen, or as a gross debulking specimen and a marginal specimen free of gross disease (as in case shown). The gross specimen may be submitted for vertical section histologic analysis to assess for adverse histologic features impacting tumor staging, such as perineural invasion, which may not have been appreciated on initial biopsy. Orientation nicks, sutures, or other markings must be placed at dividing points of preplanned tissue blocks (see Step 3) on both the marginal aspect of the resected specimen and the edges of the wound bed (Figure 4). Operative and specimen photographs can further clarify the specimen orientation with respect to the operative field, but should not be used in place of orientation marks on the specimen and the wound bed.
Appearance of the wound bed after removal of all gross tumor in Step 1, with dividing marks in place on patient and on planned marginal specimen, including a double nick at 12 o’clock. The diving marks are placed such that each tissue block will be no more than 2.5 × 5 cm when cut along the blue lines shown. This ensures that sections of each block can fit on a standard glass microscope slide, which has a viewing surface of 2.5 × 5 cm.
Citation: Journal of the National Comprehensive Cancer Network 22, 9; 10.6004/jnccn.2024.7037
Step 2
A marginal tissue disc is created, inked, and divided, preserving orientation relative to the wound bed (Figure 5). If the marginal specimen is not created by the surgeon, the tissue specimen may be handed off the field and the marginal specimen can be created by another individual trained in PDEMA, such as a surgical or pathology technician. Creating a marginal specimen from an en bloc specimen requires shaving the marginal aspect away from the block in a single piece, which is then subdivided. The marginal surface is ideally inked (Figure 6) before it is shaved from an en bloc specimen and cut into blocks (Figure 7) so that it is clear which surface is marginal on each block. The inking and subdivision of the marginal disc into blocks should be completed in the operating room by the surgeon or a delegated assistant, as described earlier, to ensure that the surgeon is certain of the relation of each block to the wound bed and the orientation markers placed in Step 2. Each tissue block should be no more than 2.5 × 3 cm and approximately 2- to 3-mm thick for proper fitting into a cassette, fixation in formalin, and later, sectioning onto standard glass microscope slides (Figure 7).
Two debulking specimens (left) including a deep focus of gross tumor (inferior); excised marginal disc (right).
Citation: Journal of the National Comprehensive Cancer Network 22, 9; 10.6004/jnccn.2024.7037
The marginal surface of the marginal tissue disc is inked by the surgeon or assistant. This is the surface that will be cut and visualized by the pathologist because this is the surface relevant for margin assessment. The marginal tissue disc is transferred in correct orientation with under surface inked black as shown. The pathologist may use their usual standards for dividing into blocks (refer to Figures 7 and 8), orienting blocks relative to one another, using additional inks as necessary and ensuring that each block is embedded such that it will be cut from the inked marginal surface and parallel to the marginal surface, which is the true deep margin. Care should be taken to cut sections that visualize the entire marginal surface, without fragmentation or holes, and without cutting deeply into the block away from the margin.
Citation: Journal of the National Comprehensive Cancer Network 22, 9; 10.6004/jnccn.2024.7037
(A, B) The marginal disc is divided into tissue blocks <2.5 × 3 cm and approximately 2- to 3-mm thick as designated by the diving nicks in Figure 4 so that each tissue block can each fit on a standard glass slide when it is cut in the pathology laboratory (shown here for demonstration only—glass slides are not needed in the operating room).
Citation: Journal of the National Comprehensive Cancer Network 22, 9; 10.6004/jnccn.2024.7037
Step 3
Each marginal tissue block is placed in a cassette, preserving orientation. Each cassette must be labeled individually to designate the tissue piece that it contains, as per the guidelines of the pathology laboratory (Figure 8). The inked marginal surface is placed face down (and additionally marked “_M” in this example) to preserve orientation. Such orientation and labeling protocols must be clarified between surgeons and pathologists and be consistent across a given institution.
(A, B) Each tissue block is placed into a tissue cassette designating the block number (block 2 in this example). The marginal surface is placed face down per convention (labeled “_M” in this example).
Citation: Journal of the National Comprehensive Cancer Network 22, 9; 10.6004/jnccn.2024.7037
Step 4
A schematic map is created by a surgeon or assistant showing the location of each tissue block relative to the wound bed. The map must be labeled similarly to the cassettes, identifying each tissue block and conveying its orientation relative to the wound bed (Figure 9A). This map should ideally accompany the cassettes to the pathology laboratory. A photograph or copy of the map should be maintained as part of the surgical record.
The tissue cassettes are placed in formalin bottles with appropriate labeling and sent to pathology for next-day paraffin embedding, which solidifies the tissue. (A) A schematic map is made showing the location of each tissue block relative to the wound bed. The map reflects the labeling scheme as seen in Figures 6–8 for each tissue block. This map or a copy accompanies the tissue blocks when sent to pathology. The hardened tissue blocks are then cut en face along the inked marginal surface, not vertically, into thin sections, placed on glass slides, stained with hematoxylin-eosin, and read by a pathologist experienced in cutaneous cancers. (B) The pathologist marks positive areas, noting the tissue planes of residual tumor, and discusses the findings with the surgeon, ideally while returning the map to him/her so as to avoid miscommunication.
Citation: Journal of the National Comprehensive Cancer Network 22, 9; 10.6004/jnccn.2024.7037
Step 5
Tissue is processed and interpreted by a physician with expertise in dermatopathology. The findings are relayed to the surgeon such that they can precisely resect any areas of residual tumor within the wound bed. In Tubingen PDEMA, the tissue blocks generally undergo overnight fixation in formalin and are embedded in paraffin wax the next day. Alternatively, high-quality frozen sections may be used as is done in Mohs. However, this may impractically prolong anesthesia time for large resections. As in Mohs, the marginal surface of each tissue section is cut into thin sections, placed on glass slides, and stained with hematoxylin-eosin. In select cases, immunohistochemistry staining is performed if indicated. Once the tissue sections have been evaluated by a pathologist, the results must be precisely conveyed to the surgeon. The pathologist (or the surgeon if preferable) marks the schematic map and the pathologist and surgeon discuss the findings (Figure 9B). This discussion reviews the marked map and details of positive regions, including tissue blocks involved, the tissue plane of involvement (eg, dermis, fat, muscle, galea), and any special features (eg, perineural or lymphovascular invasion). An example of positive deep margin via en face sectioning is shown in Figure 10.
Shown here is an example (from another case) of a positive deep margin via en face sectioning. Well-differentiated squamous cell carcinoma is seen within muscle and is involving the deep margin, but is not involving peripheral margin of the dermis and epidermis (hematoxylin-eosin, original magnification ×20).
Citation: Journal of the National Comprehensive Cancer Network 22, 9; 10.6004/jnccn.2024.7037
Steps 6+
Steps 1–5 are repeated with targeted resection of any positive regions, utilizing a new orientation map each time, until margins are clear (Figure 11). The final wound can then be reconstructed once clear margins are confirmed.
(A) The surgeon excises additional tissue from the positive regions as shown in blue, using the tissue diving marks, the map, and the discussion with pathologist to ensure the correct locations. The surgeon ensures that sufficient width is taken around the positive areas, but not excising more tissue than considered necessary to achieve this. (B) The surgeon makes another schematic map to reflect the orientation of the new tissue blocks relative to the wound bed and submits this with the tissue cassettes, repeating the processes outlined earlier. Note: Tissue blocks without a skin edge (such as the superior specimen in this example) require inking of one lateral edge in a different color than the marginal surface to preserve orientation (superior edge marked blue in the diagram; surgeon/assistant would ink that edge blue). For blocks with a skin edge, the dermis and epidermis (which appear distinct under the microscope) provide the orientation. The processes described in Figures 6–9 are repeated until margins are clear, at which time the wound may be reconstructed.
Citation: Journal of the National Comprehensive Cancer Network 22, 9; 10.6004/jnccn.2024.7037
A multisurgeon team can also be used to resect extensive cases, such as the one shown in Figure 12. In this case, a Mohs surgeon cleared the peripheral margin under local anesthesia in an outpatient setting and a temporary closure was used for hemostasis. The central tumor was then resected by a surgeon with head and neck expertise under sedation, and the deep margin was processed horizontally (en face) for complete margin visualization, thus achieving PDEMA.
(A–C) A multisurgeon team can resect extensive cases such as shown in this example of recurrent DFSP on the temple. A Mohs surgeon cleared the peripheral margin under local anesthesia in an outpatient setting and a temporary closure was used for hemostasis. The central tumor was then resected by a head and neck surgeon under sedation. The deep margin was processed horizontally (en face) for complete margin visualization, thus achieving PDEMA.
Abbreviations: DFSP, dermatofibrosarcoma protuberans; PDEMA, peripheral and deep en face margin assessment.
Citation: Journal of the National Comprehensive Cancer Network 22, 9; 10.6004/jnccn.2024.7037
Additional Considerations
For skin cancers in areas with undulating topography, such as ear, eyelid, and vulva, tissue division into blocks and schematic mapping of the marginal surface can be more complicated, making the implementation of PDEMA more challenging. Precise margin assessment is all the more critical in these areas. Precise inking of the marginal surface, tissue block division, wound bed orientation markers, and mapping may all require additional thought.
There are 2 specific scenarios in which some aspect of the marginal surface may not be evaluable via PDEMA: (1) named nerve invasion: margins involving tumor extension within large, named nerves can be assessed by dissecting the nerve, excising as long a portion of it as is feasible, and sectioning the proximal end of the nerve in cross section for histologic evaluation; and (2) bone resections: these may be fragmented which complicates en face assessment. PDEMA may be incomplete in such cases, but the remainder of the marginal surface is still assessed via PDEMA.
Surgeons and pathologists are encouraged to review the PDEMA checklist provided by the NCCN. All 5 categories must be marked “Yes” to achieve PDEMA. If any of the 5 items is marked “No,” the procedure does not achieve PDEMA.18
- 1.Is the entire peripheral marginal surface of the surgical specimen microscopically visualized?
- 2.Is the entire deep marginal surface of the surgical specimen microscopically visualized?
- 3.Is the surgical specimen oriented to the wound bed and marked such that any positive margin identified in histopathologic analysis can be accurately located and re-excised?
- 4.Is the process of excision and complete histologic examination repeated until no further cancer is identified or until further excision is no longer in the best interest of the patient?
- 5.Is the process rapid enough for optimal patient management to prevent distortion of the wound bed that would decrease accuracy of tissue orientation?
Conclusions
PDEMA is NCCN’s preferred treatment for DFSP, high-risk BCC, and very-high-risk cSCC. In the United States, Tubingen PDEMA has not been widely used for such cases due to an absence of standardized protocols and education in PDEMA techniques. This article described the key features of PDEMA that allow for complete margin evaluation. To ensure success, centers treating DFSP, high-risk BCC, and very-high-risk cSCC are encouraged to develop a Tubingen PDEMA protocol similar to the one detailed herein. All providers involved in handling marginal specimens (ie, surgeons, pathologists, surgery and laboratory technicians) should understand the rationale for each center’s specific protocol, and for PDEMA in general. The hope is that the present outline will assist each center in developing Tubingen PDEMA protocols to achieve adherence with NCCN Guidelines.
Acknowledgments
We greatly appreciate Dr. Brooke Walls at Aspen Dermatology for sharing her illustrations in Figure 1, Figure 2A, and Figure 2B.
References
- 1.↑
Mosterd K, Krekels GA, Nieman FH, et al. Surgical excision versus Mohs’ micrographic surgery for primary and recurrent basal-cell carcinoma of the face: a prospective randomised controlled trial with 5-years’ follow-up. Lancet Oncol 2008;9:1149–1156.
- 2.↑
van Loo E, Mosterd K, Krekels GA, et al. Surgical excision versus Mohs’ micrographic surgery for basal cell carcinoma of the face: a randomised clinical trial with 10 year follow-up. Eur J Cancer 2014;50:3011–3020.
- 3.↑
Rowe DE, Carroll RJ, Day CL Jr. Prognostic factors for local recurrence, metastasis, and survival rates in squamous cell carcinoma of the skin, ear, and lip. Implications for treatment modality selection. J Am Acad Dermatol 1992;26:976–990.
- 4.↑
Leibovitch I, Huilgol SC, Selva D, et al. Cutaneous squamous cell carcinoma treated with Mohs micrographic surgery in Australia I. Experience over 10 years. J Am Acad Dermatol 2005;53:253–260.
- 5.↑
Pugliano-Mauro M, Goldman G. Mohs surgery is effective for high-risk cutaneous squamous cell carcinoma. Dermatol Surg 2010;36:1544–1553.
- 6.↑
Fraga SD, Besaw RJ, Murad F, et al. Complete margin assessment versus sectional assessment in surgically excised high-risk keratinocyte carcinomas: a systematic review and meta-analysis. Dermatol Surg 2022;48:704–710.
- 7.↑
Massey PR, Gupta S, Rothstein BE, et al. Total margin-controlled excision is superior to standard excision for keratinocyte carcinoma on the nose: a Veterans Affairs nested cohort study. Ann Surg Oncol 2021;28:3656–3663.
- 8.↑
Martin ECS, Vyas KS, Batbold S, et al. Dermatofibrosarcoma protuberans recurrence after wide local excision versus Mohs micrographic surgery: a systematic review and meta-analysis. Dermatol Surg 2022;48:479–485.
- 9.↑
Kim SJ, Thompson AK, Zubair AS, et al. Surgical treatment and outcomes of patients with extramammary Paget disease: a cohort study. Dermatol Surg 2017;43:708–714.
- 10.↑
Breuninger H, Schaumburg-Lever G. Control of excisional margins by conventional histopathological techniques in the treatment of skin tumours. An alternative to Mohs’ technique. J Pathol 1988;154:167–171.
- 11.↑
Breuninger H, Thaller A, Schippert W. Subclinical spread of dermatofibrosarcoma protuberans and resulting treatment modalities. Hautarzt 1994;45:541–545.
- 12.↑
Möhrle M, Breuninger H. The Muffin technique—an alternative to Mohs’ micrographic surgery. J Dtsch Dermatol Ges 2006;4:1080–1084.
- 13.↑
Veronese F, Boggio P, Tiberio R, et al. Wide local excision vs. Mohs Tübingen technique in the treatment of dermatofibrosarcoma protuberans: a two-centre retrospective study and literature review. J Eur Acad Dermatol Venereol 2017;31:2069–2076.
- 14.↑
Centre for Evidence-Based Medicine. OCEBM 2011 Levels of Evidence. Accessed September 9, 2023. Available at: https://www.cebm.ox.ac.uk/resources/levels-of-evidence/ocebm-levels-of-evidence
- 15.↑
Tromovitch TA, Stegeman SJ. Microscopically controlled excision of skin tumors. Arch Dermatol 1974;110:231–232.
- 16.↑
Farma JM, Ammori JB, Zager JS, et al. Dermatofibrosarcoma protuberans: how wide should we resect? Ann Surg Oncol 2010;17:2112–2118.
- 17.↑
Schmults CD, Blitzblau R, Aasi SZ, et al. NCCN Clinical Practice Guidelines in Oncology: Dermatofibrosarcoma Protuberans. Version 2.2023. Accessed September 9, 2023. To view the most recent version, visit https://www.nccn.org
- 18.↑
Schmults CD, Blitzblau R, Aasi SZ, et al. NCCN Clinical Practice Guidelines in Oncology: Squamous Cell Skin Cancer. Version 1.2023. Accessed September 9, 2023. To view the most recent version, visit https://www.nccn.org
- 19.↑
Bordeaux J, Blitzblau R, Aasi SZ, et al. NCCN Clinical Practice Guidelines in Oncology: Basal Cell Skin Cancer. Version 2.2024. Accessed September 24, 2023. To view the most recent version, visit https://www.nccn.org
- 20.↑
van Delft LCJ, Nelemans PJ, van Loo E, et al. The illusion of conventional histological resection margin control. Br J Dermatol 2019;180:1240–1241.
- 21.↑
Paoli J, Cogrel O, van der Geer S, et al. ESMS Position Document on the Use of Mohs Micrographic Surgery and Other Micrographic Surgery Techniques in Europe. Accessed January 29, 2023. Available at: https://ems-mohs.eu/fileadmin/user_upload/ESMS_Position_Paper_-_WEB.pdf
- 22.↑
Danesh MJ, Menge TD, Helliwell L, et al. Adherence to the National Comprehensive Cancer Network criteria of complete circumferential peripheral and deep margin assessment in treatment of high-risk basal and squamous cell carcinoma. Dermatol Surg 2020;46:1473–1480.
- 23.↑
Sable KA, Rudningen KE, Lasarev MR, et al. Exploring knowledge gaps in the understanding of peripheral and deep en face margin assessment. Arch Dermatol Res 2023;315:2683–2687.
- 24.↑
Rowe DE, Carroll RJ, Day CL Jr. Mohs surgery is the treatment of choice for recurrent (previously treated) basal cell carcinoma. J Dermatol Surg Oncol 1989;15:424–431.
- 25.↑
Leigheb M, Zavattaro E, Bellinzona F, et al. Micrographic surgery (Tubingen torte technique) for the treatment of an invasive dermatofibrosarcoma protuberans with muscular involvement. G Ital Dermatol Venereol 2010;145:309–311.
- 26.↑
Cammarata E, Esposto E, Veronese F, et al. Safety margins for dermatofibrosarcoma protuberans: a comparison between wide local excision and Mohs Tubingen technique. Eur J Dermatol 2020;30:289–293.
- 27.↑
Volanis D, Neal DE, Warren AY, et al. Incidence of needle-tract seeding following prostate biopsy for suspected cancer: a review of the literature. BJU Int 2015;115:698–704.
- 28.↑
Barrientos-Ruiz I, Ortiz-Cruz EJ, Serrano-Montilla J, et al. Are biopsy tracts a concern for seeding and local recurrence in sarcomas? Clin Orthop Relat Res 2017;475:511–518.
- 29.↑
Siddiqi MA, Kim HS, Jede F, et al. Association of core needle biopsy tract resection with local recurrence in extremity soft tissue sarcoma. Skeletal Radiol 2017;46:507–512.
- 30.↑
Turkoz KH, Erol B, Seven IE. Tumor cell seeding in the biopsy tract and its clinical significance in osteosarcomas. J Surg Oncol 2018;118:1335–1340.
- 31.↑
Berger-Richardson D, Swallow CJ. Needle tract seeding after percutaneous biopsy of sarcoma: risk/benefit considerations. Cancer 2017;123:560–567.
- 32.↑
Mighell AJ, High AS. Histological identification of carcinoma in 21 gauge needle tracks after fine needle aspiration biopsy of head and neck carcinoma. J Clin Pathol 1998;51:241–243.
- 33.↑
Rogers HW, Coldiron BM. Analysis of skin cancer treatment and costs in the United States Medicare population, 1996–2008. Dermatol Surg 2013;39:35–42.
- 34.↑
Wang DM, Morgan FC, Besaw RJ, et al. An ecological study of skin biopsies and skin cancer treatment procedures in the United States Medicare population, 2000 to 2015. J Am Acad Dermatol 2018;78:47–53.
