Plus Slides are made by a process that places a permanent positive charge on the slide. Tissue sections adhere better to Plus glass slides without the need for labor intensive special adhesives or protein coatings. Plus slides virtually eliminate background staining in standard H&E stains.

Subcutaneous adipose tissue is difÞcult to cut. InÞltration by tumors makes it easier to cut the sections due to the surrounding tumor stroma. Mohs technicians usually freeze the tissue to a colder degree and cut thicker sections in order to obtain a good Mohs slide with adipose tissue.

Summary: Conclusion

¥The success of MMS depends on the correct interpretation of Mohs slides.

¥Tumor recurrence may result from missing a focus of tumor or evaluating a suboptimal slide with missing pieces of tissue. However, over reading can result in unnecessary extra stages that will produce a larger Mohs defect.

¥Technical errors are the most common cause of local recurrence after MMS.

13.4Conclusion

The high rate of cure associated with MMS is contingent upon different surgical and laboratory steps. Thorough and correct interpretation of Mohs slides is probably the most important step in the Mohs technique. Missing a focus of tumor or evaluating a suboptimal slide with missing pieces of tissue may result in tumor recurrence. Over reading due to lack of experience identifying different cutaneous structures such as a bulge or a mantle will result in unnecessary extra

stages which will produce a larger Mohs defect. Proper training of Mohs fellows, dermatology residents, and young dermatologists in dermatopathology and particularly in skin frozen section interpretation is very important for the practice of MMS. Finally, it is important to note that technical errors represent the most common cause of local recurrence after MMS.

References

1. Mariwalla K, Aasi SZ, Glusac EJ, Leffell DJ. Mohs micrographic surgery histopathology concordance. J Am Acad Dermatol. 2009;60(1):94Ð8.

2.Hruza GJ. Mohs micrographic surgery local recurrences. J Dermatol Surg Oncol. 1994;20:573Ð7.

3. Yu Y, Finn DT. Crescent versus rectangle: is it a true negative margin in second and subsequent stages of Mohs surgery? Dermatol Surg. 2010;36(2):171Ð6.

4. Whalen J, Leone D. Mohs micrographic surgery for the treatment of malignant melanoma. Clin Dermatol. 2009;27(6): 597Ð602.

5. Mehrany K, Byrd DR, Roenigk RK, et al. Lymphocytic inÞltrates and subclinical epithelial tumor extension in patients with chronic leukemia and solid-organ transplantation. Dermatol Surg. 2003;29:129Ð34.

6. Katz KH, Helm KF, Billingsley EM, et al. Dense inßammation does not mask residual primary basal cell carcinoma during Mohs micrographic surgery. J Am Acad Dermatol. 2001;45:231Ð8.

7. Albregts T, Orengo I, Salasche S, et al. Squamous cell carcinoma in a patient with chronic lymphocytic leukemia. An intraoperative diagnostic challenge for the Mohs surgeon. Dermatol Surg. 1998;64:269Ð72.

8.Tuttle MS, Rosenberg AS, WinÞeld HL, Somach SC. Pseudocarcinomatous hyperplasia with follicular differentiation overlying basal cell carcinoma. Am J Dermatopathol.

2009;31(6):557Ð60.

9. Cochran AJ. The incidence of melanocytes in normal skin. J Invest Dermatol. 1970;55:65Ð70.

10. Dean NR, Brennan J, Haynes J, et al. Immunohistochemical labeling of normal melanocytes. Appl Immunohistochem Mol Morphol. 2002;10:199Ð204.

11. Gilchrest BA, Blog FB, Szabo G. Effects of aging and chronic sun exposure on melanocytes in human skin. J Invest Dermatol. 1979;73:141Ð3.

12. Toda K, Kathak MA, Parrish JA, et al. Alteration of racial differences in melanosome distribution in human epidermis after exposure to ultraviolet light. Nature. 1972;236:143Ð5.

13. Hendi A, Brodland DG, Zitelli JA. Melanocytes in longstanding sun-exposed skin: quantitative analysis using the MART-1 immunostain. Arch Dermatol. 2006;142(7): 871Ð6.

14. Zitelli JA, Brown CD, Hanusa BH. Surgical margins for excision of primary cutaneous melanoma. J Am Acad Dermatol. 1997;37(3 Pt 1):422Ð9.

15. Zalla MJ, Lim KK, Dicaudo DJ, Gagnot MM. Mohs micrographic excision of melanoma using immunostains. Dermatol Surg. 2000;26:771Ð84.

16. Florell SR, Zone JJ, Gerwels JW. Basal cell carcinomas are populated by melanocytes and Langerhans cells. Am J Dermatopathol. 2001;23(1):24Ð8.

17. Whiting DA. Histology of normal hair. In: Hordinsky MK, Sawaya ME, Scher RK, editors. Atlas of hair and nails. Philadelphia: Churchill Livingstone; 2000. p. 17.

18.Ackerman AB, Reddy VB, Soyer HP. Anatomic, histologic, and biological aspects. In: Neoplasms with follicular differentiation. New York, NY: Ardor Scribendi Publishers; 2001.

p. 80.

19. Hassanein AM, Al-Quran SZ, Kantor GR, et al. ThomsenFriedenreich (T) antigen: a possible tool for differentiating sebaceous carcinoma from its simulators. Appl Immunohistochem Mol Morphol. 2001;9(3):250Ð4.

20.Hassanein AM. Sebaceous carcinoma and the T-antigen. Semin Cutan Med Surg. 2004;23(1):62Ð72.

21.Rao NA, Hidayat AA, McLeon IW. Sebaceous carcinomas of the ocular adnexa: a clinicopathologic study of 104 cases, with Þve-year follow-up data. Hum Pathol. 1982;13:113Ð22.

22.Holecek B-U, Ackerman AB. Bulge-activation hypothesis: is it valid? Am J Dermatopathol. 1993;15:235.

23. Herman KL, Kantor GR, Katz SM. Squamous cell carcinoma in situ overlying dermatoÞbroma. J Cutan Pathol. 1990;17(6):385Ð7.

24.Hassanein AM, Proper SA, Depcik-Smith ND, Flowers FP. Peritumoral Þbrosis in basal cell and squamous cell carcinoma mimicking perineural invasion: potential pitfall in Mohs micrographic surgery. Dermatol Surg. 2005;31(9 Pt 1):1101Ð6.

25.Abbas O, Bhawan J. Cutaneous perineural inßammation: a review. J Cutan Pathol. 2010;37(12):1200Ð11.

26. Moehrle M, Breuinger H, Schippert W, HŠfner HM. Letter: Imiquimod 5% cream as adjunctive therapy for primary, solitary, nodular basal cell carcinomas before Mohs micrographic surgery: a randomized, double-blind, vehicle-con- trolled study. Dermatol Surg. 2010;36(3):428Ð30.

J.S. Youse • R.H. Cook-Norris • R.M. Knudson Department of Dermatology,

Mayo Clinic, Rochester, MN, USA e-mail: youse.jeremy@mayo.edu;

cooknorris.robert@mayo.edu and knudson.richelle@mayo.edu

R.K. Roenigk (*)

Consultant, Department of Dermatology,

Mayo Clinic, Rochester, Minnesota;

Professor of Dermatology, College of Medicine,

Mayo Clinic. Rochester, Minnesota, 55905, USA

Abbreviations

Summary: History

•Proper identification, labeling, and documentation of patients and tissue samples are important aspects of patient safety.

•System-based quality improvement offers a systematic approach to reducing medical errors in all medical specialties, including dermatology and MMS.

•Simple medical procedures, such as obtaining a skin biopsy, are fraught with many potential medical errors, especially errors associated with misidentification and mislabeling.

14.1History

In the past several decades, patient safety and medical errors have become the focus of broad quality improvement initiatives. System-based quality improvement has evolved into a driving force within the field of medicine, in part as a result of the high number of medical errors uncovered by a 1999 Institute of Medicine report [1]. System-based improvements have focused on proper patient identification, specimen handling, medication errors, and result reporting, among others. These system-based improvements are pertinent to MMS practices for two reasons. First, system-based quality measures such as proper identification of patients and tissues reduce medical errors and lead to improved patient care. Proper identification of patients and tissue specimens is perhaps the most important system-based quality measurement in dermatology and MMS practices. The simple act of obtaining a skin biopsy and submitting the specimen for pathologic evaluation has the potential for dozens of medical errors, some of which may cause the patient serious harm. Recently, the dermatology literature has emphasized medical errors related to the transfer of patient care and tissue specimens between providers [2].

Continuum of Care for a Patient with a Presumed Malignant Melanoma

1. PCP (primary care provider) sees patient and places dermatology referral for suspect pigmented lesion.1

2. Patient keeps the appointment and is seen by the dermatologist, and a biopsy is performed.

3. The specimen is labeled and requisition form is completed.*

4. The specimen is placed in a bin for the pathology courier.*

5. The courier signs for the specimen and transports it to the laboratory.*

6.The dermatopathology laboratory receives the specimen and enters it into their computer system.*

7. A technician grosses the specimen and places it into a labeled cassette for processing.*

8. The gross dictation is sent to transcription.*

9. A histology technician places the cassette into a tissue processor.*

10.After processing, a technician embeds each piece of the tissue in a correctly labeled block.*

11.Sections are cut from the paraffin blocks and placed on correctly labeled slides.*

12. The labeled slide is stained, and a cover slip is applied.

13.The slides are reunited with the correct paperwork and delivered to the pathologist.*

14.The pathologist reviews the slides and dictates or enters a diagnosis into a computer program.*

15. If the report is dictated rather than entered directly into a computer, it must pass to transcription;* then the completed report is returned to the pathologist for review and signature.*

16. The report is generated and sent to the dermatologist on paper or electronically.*

17.The dermatologist contacts the patient and sends a message to the appointments pool to schedule an appointment for definitive treatment.*

18.The diagnosis and treatment plan are communicated to the PCP.

19.Treatment is completed.*

20.The appropriate interval of follow-up is scheduled.*

21.The patient keeps all subsequent follow-up appointments.*

Patient identity and specimen labeling are important sources of medical errors in this process. Eliminating medical errors associated with these handoff points in a patient’s care is vital to improving overall patient safety. The second reason system-based improvements are important to MMS is the requirement for a welldeveloped written manual detailing the policies and processes for collection, labeling, processing, evaluation, reporting, and storage of tissue specimens in order to obtain laboratory certification by oversight bodies.

Summary: Regulation and Certification

•The Clinical Laboratory Improvement Amendments (CLIA) sets basic quality standards for medical laboratories.

•Under CLIA, MMS practices are considered high-complexity laboratories.

•There are multiple organizations associated with medical laboratory accreditation.

•Many resources are available to assist MMS practices with the laboratory accreditation process.

14.2Regulation and Certification

In 1988, the federal government passed the Clinical Laboratory Improvement Amendments (CLIA). These amendments were established to set quality standards and to ensure the integrity of medical laboratories. CLIA requires that medical laboratories be certified by the Secretary of the Department of Health and Human Services. CLIA defines a laboratory as any facility used for the testing and examination of human-derived tissue for the purpose of providing information for the diagnosis, prevention, or treatment of disease. Different levels of CLIA certification are given on the basis of the complexity of testing performed. CLIA stratifies the levels of certification into the following categories: waiver of certification, provider-performed microscopy procedures, moderate complexity, and high complexity. Laboratories involved in complex testing processes, such as histopathology, immunohistochemistry, microbiology, blood chemistries, and others, are considered as “High Level of Complexity” under CLIA. MMS laboratories are included in this high-complexity classification. Application for CLIA certification may be done through state CLIA offices or via an alternative private physician-directed accreditation program, such as COLA(CommissiononOfficeLaboratoryAccreditation) or the College of American Pathologists (CAP). These organizations have been granted authority to inspect clinical laboratories and issue accreditation. In short, CLIA certification requires the laboratory to meet various quality standards for facility safety, process quality assessment, personnel training, and proficiency testing and to agree to routine inspections every 2 years [3–6].

This chapter is meant to highlight the importance of proper methods for documentation, record keeping, and storage of tissue specimens for MMS practices and to provide guidance and a starting point for obtaining accreditation. A detailed discussion of CLIA certification requirements and accreditation processes is beyond the scope of this chapter. Regulations vary from state to state; contact your state CLIA office, COLA, or the College of American Pathologists [7] for detailed information (www.cms.hhs.gov/CLIA/downloads/ CLIA.SA.pdf). For an MMS surgeon in a solo practice, the accreditation process may seem arduous and complicated. However, other additional resources and organizations are available to simplify and streamline the accreditation process (see “Additional Resources”).

Summary: CLSI and Path of Workflow

•The Clinical and Laboratory Standards Institute (CLSI) is an international organization dedicated to developing best practice guidelines for collection, processing, and documentation of tissue specimens.

•CLSI organizes clinical laboratory processes into three phases: preexamination, examination, and postexamination.

•The CLSI framework for clinical laboratory processes, also called the total testing process, or path of workflow, can be easily applied in MMS labs.

14.3CLSI and Path of Workflow

The Clinical and Laboratory Standards Institute (CLSI, formerly National Committee for Clinical Laboratory Standards) is an international organization dedicated to development of consensus guidelines and standards for patient examination. Given the broad consensus obtained in their development, CLSI standards are used as a model for most laboratories to assist with development of best practices for proper collection, processing, documentation, and storage of tissue specimens [8–11]. Sample documents available from CLSI are a valuable reference in the development of a complete policy and procedure manual. CLSI regularly updates numerous