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Minimal deviation melanoma
CANCER TREATMENT REVIEWS 2002; 28: 219–221 doi:10.1016/S0305-7372(02)00035-X, available online at http://www.idealibrary.com on
TUMOUR REVIEW
Minimal deviation melanoma Y. D. Podnos, J. C. Jimenez, K. Zainabadi, J. G. Jakowatz and R. J. Barr Department of Surgery, Irvine Medical Center, University of California, Orange County, CA, USA Minimal deviation melanomas (MDM) are poorly characterized, uncommon naevomelanocytic tumours that are thought to represent part of the continuum from benign atypical naevi to frank malignant melanomas. Exactly where on that continuum they stand and who is most affected remains controversial. The few studies classifying MDM pointed to a less aggressive nature. Furthermore, it is thought that MDM affects patients in the fourth and fifth decades of life. In a recent review conducted at our institution, medical records of all patients with melanoma diagnosed at a tertiary care university medical center between January 1997 and May 2000 were reviewed to identify those with MDM. Those with MDM were examined to determine subtype, age and sex distributions, and location of tumour and findings were compared to those in the published literature. Unlike previous studies, the mean age of patients with MDM was 27 years with 20/31 being under 30 years old. Our results support prior findings that MDM is less aggressive than typical malignant melanomas in that only 1/5 undergoing lymphatic mapping had a positive node. Despite its description more than 30 years ago, MDM remains a poorly understood pathologic entity. Further study in such techniques as sentinel lymph node mapping and determination of angiogenesis factors is warranted to give insight as to what features predict an aggressive nature and to identify prognostic factors. c 2002 Elsevier Science Ltd. All rights reserved. s
INTRODUCTION Minimal deviation melanomas (MDM) are uncommon, poorly characterized naevomelanocytic tumours distinguished histologically by expansive growth of atypical naevomelanocytes with expansion into the reticular layer of the dermis (ClarkeÕs level IV). The vertical growth phase has a less pronounced cellular atypia than that seen in melanoma, instead demonstrating regularly arranged fascicles of uniform, atypical cells (1). Because of their resemblance to malignant melanoma, it is believed that MDM represents a point somewhere in the continuum between benign skin neoplasms and the typical, biologically aggressive malignant melanoma (2). Historically, MDMs were thought to afflict people primarily in the fourth and fifth decades of life and have a more indolent clinical course, rarely causing Correspondence to: J.G. Jakowatz MD, Associate professor, Department of Surgery, Irvine Medical Center, University of California, 101 The City Dr. Building 23, Route 81, Orange County, CA 92868, USA; E-mail: [email protected]
metastases and having a relatively improved outcome compared to malignant melanoma. This latter point is clinically important, as physicians recommend less extensive surgical management for less aggressive tumours. Since its initial description by Reed et al. (3) in 1975, minimal deviation melanoma (MDM) has received very little attention in the surgical literature. In the pathology literature, however, much attention was paid to MDM in the 1980s, as pathologists struggled with the characterization of melanomas, in search of a diagnosis other than melanoma that would reflect the more indolent nature of MDMs and not necessitate radical surgery. This was especially important given that these tumours occur in younger patients. In a recent study conducted at our institution, each patient with melanoma between January 1997 and May 2000 was retrospectively reviewed to determine those with a primary diagnosis of minimal deviation melanoma. Chart review revealed data regarding demographics, tumour size, tumour location, depth of invasion, occurrence of known metastatic disease, and any additional procedures undertaken (i.e.
c 2002 ELSEVIER SCIENCE LTD. ALL RIGHTS RESERVED. 0305-7372/02/$ - see front matter s
220
lymphatic mapping). The results were tabulated and compared with previously published data. A total of 1730 patients were identified as having melanoma. Thirty-one (1.7%) of these patients had MDM as their primary diagnosis. Fifty-eight percent (n ¼ 18) were in women while 43% (n ¼ 13) were found in men. The mean age was 26.6 years (range 9–69 years). Dimensions range from 4 to 17 mm in diameter. All lesions were ClarkeÕs level IV, with Breslow thickness ranging from 0.6 to 2.5 mm (mean 1.38 mm). Subtypes seen were Spitz (n ¼ 8), halo (n ¼ 6), spindle (n ¼ 4), spindle/epithelioid (n ¼ 4), dermal (n ¼ 3), naevoid (n ¼ 2), and desmoplastic (n ¼ 1). No subtype was identified in 3 patients. Locations included back (n ¼ 8), leg (n ¼ 7), arm/ shoulder (n ¼ 5), face (n ¼ 4), foot (n ¼ 3), scalp (n ¼ 2), chest/abdomen (n ¼ 2), and posterior neck (n ¼ 1). A single patient had two lesions. Five patients underwent sentinel lymph node mapping with metastatic melanoma found in a single node in just one patient. Originally MDM was thought to occur in the fourth and fifth decades of life, our results are significant because in our experience, the largest to date, the mean age is more than 14 years younger than previously described. MDMs fall somewhere on the continuum between benign nevi and frank melanomas. This ‘‘Common Final Pathway’’ theory, asserting that malignant melanomas arise from preexisting benign lesions, was first proposed in 1987. This is supported by evidence of MDM remnants or other less invasive pathology at the borders of melanomas and the
Y. D. PODNOS ET AL.
similarity of immunologic markers between MDM and malignant melanoma (4). Even within MDM, subtypes as seen in this study population occur that are named according to the types of benign nevus cells seen on the outside borders. In the progression from benign naevomelanocytic lesion to malignant melanoma, a logical, stepwise chain of events has been postulated (1). First, nevus cells appear at the apexes of rete ridges, from which they descend into the dermis. During this process, there is a loss of junctional and dermal components, leaving only naevomelanocytic components. As increasing atypia occurs, the cells lose their dendrites and less melanin is seen in the cytoplasm. Their shape changes from polygonal to round and, at this point, there is a transition from Type A to Type B naevomelanocytes. As they invade the reticular dermis, elongate, and proliferate, they become Type C naevomelanocytes. By definition, MDMs must have invasion into the reticular dermis (Clarke level IV). As compared to melanoma, they have less cellular atypia in the vertical growth element. Melanomas are notorious for having more cellular pleomorphism, increased mitotic activity, and larger nuclear to cytoplasmic ratios. Additionally, melanomas show less maturation and can infiltrate deeper dermal layers as single cells. MDM invades as broad fascicles (Figs. 1 and 2) (1). In contrast to malignant melanoma, in which the risks of metastasis include thickness, microscopic 2 satellitosis, and >6 mitoses=mm , the metastatic potential of MDM is still unknown. Several case reports
Figure 1 The epidermis is mildly atrophic without a significant junctional component. No pagetoid foci are present. There is no remarkable maturation identified within the dermal component (H&E, X100).
MINIMAL DEVIATION MELANOMA
221
Figure 2 Higher magnification exhibiting round nevic-type cells with some pleomorphism and small nuclei (H&E, X200).
of a primary MDM lesion with metastatic melanoma have been reported. The single positive lymph node mapping in our sample also showed melanoma in the node. These cases illustrate the concept of a ‘‘final common pathway’’ in melanoma genesis in that the bulk of the tumour was MDM while other parts that became metastatic could have already evolved into melanoma. Despite the ‘‘final common pathway’’ theory, MDM remains a less virulent neoplasm. Phillips et al. (1) examined 18 patients with MDM with only 2 (11%) dying from metastatic disease over a mean follow up period of 57 months. It is not known if the metastatic lesions were MDM or frank melanoma. In 8 patients presented by Barr et al. (5), there was no recurrence or mortality over a mean 16-month follow up. Our sample, though small, further confirms the lower incidence of metastasis in MDM. Therapy of MDM has been controversial ever since its description in 1975. Originally, pathologists did not want to label these lesions as melanomas, fearing radical operations and an adverse psychological response to the diagnosis by patients. With time, however, it became clear that because MDM is more indolent in nature, less invasive operations were warranted. In our experience, lymph node mapping was successful and sufficient in picking up the single metastatic lesion. One possible ex-
ception, however, are head and neck MDMs. Because of the rich vascular and lymphatic networks in those areas, a hypothetical increase in metastasis could occur (6). Clearly, further, more detailed evaluation of MDM is needed, particularly the determination of risk factors for MDM metastasis. Additionally, basic laboratory research to delineate more accurately the patholgical spectrum of benign naevi through to malignant melanoma is required.
REFERENCES 1. Phillips ME, Margolis RJ, Merot Y, et al. The spectrum of minimal deviation melanomas: a clinicopathologic study of 21 cases. Hum Path 1986; 17: 796–806. 2. Reed RJ. Minimal deviation melanoma. Hum Path 1990; 21: 1206–1211. 3. Reed RJ, Ichinose H, Clarke WH, et al. Common and uncommon melanocytic nevi and borderline melanomas. Semin Oncol 1975; 2: 119–147. 4. Reed RJ. The histologic variance of malignant melanoma: the interrelationship of histologic subtype, neoplastic progression, and biologic behavior. Pathology 1985; 17: 301–312. 5. Barr LH, Goldman LI, Solomon JA, et al. Minimal deviation melanomas. Surg Gyn Obstet 1984; 159: 546–548. 6. Becker DW, Miller CJ, Keller HB. Metastatic minimal deviation melanoma. Ann Plast Surg 1979; 4: 230–237.
TUMOUR REVIEW
Minimal deviation melanoma Y. D. Podnos, J. C. Jimenez, K. Zainabadi, J. G. Jakowatz and R. J. Barr Department of Surgery, Irvine Medical Center, University of California, Orange County, CA, USA Minimal deviation melanomas (MDM) are poorly characterized, uncommon naevomelanocytic tumours that are thought to represent part of the continuum from benign atypical naevi to frank malignant melanomas. Exactly where on that continuum they stand and who is most affected remains controversial. The few studies classifying MDM pointed to a less aggressive nature. Furthermore, it is thought that MDM affects patients in the fourth and fifth decades of life. In a recent review conducted at our institution, medical records of all patients with melanoma diagnosed at a tertiary care university medical center between January 1997 and May 2000 were reviewed to identify those with MDM. Those with MDM were examined to determine subtype, age and sex distributions, and location of tumour and findings were compared to those in the published literature. Unlike previous studies, the mean age of patients with MDM was 27 years with 20/31 being under 30 years old. Our results support prior findings that MDM is less aggressive than typical malignant melanomas in that only 1/5 undergoing lymphatic mapping had a positive node. Despite its description more than 30 years ago, MDM remains a poorly understood pathologic entity. Further study in such techniques as sentinel lymph node mapping and determination of angiogenesis factors is warranted to give insight as to what features predict an aggressive nature and to identify prognostic factors. c 2002 Elsevier Science Ltd. All rights reserved. s
INTRODUCTION Minimal deviation melanomas (MDM) are uncommon, poorly characterized naevomelanocytic tumours distinguished histologically by expansive growth of atypical naevomelanocytes with expansion into the reticular layer of the dermis (ClarkeÕs level IV). The vertical growth phase has a less pronounced cellular atypia than that seen in melanoma, instead demonstrating regularly arranged fascicles of uniform, atypical cells (1). Because of their resemblance to malignant melanoma, it is believed that MDM represents a point somewhere in the continuum between benign skin neoplasms and the typical, biologically aggressive malignant melanoma (2). Historically, MDMs were thought to afflict people primarily in the fourth and fifth decades of life and have a more indolent clinical course, rarely causing Correspondence to: J.G. Jakowatz MD, Associate professor, Department of Surgery, Irvine Medical Center, University of California, 101 The City Dr. Building 23, Route 81, Orange County, CA 92868, USA; E-mail: [email protected]
metastases and having a relatively improved outcome compared to malignant melanoma. This latter point is clinically important, as physicians recommend less extensive surgical management for less aggressive tumours. Since its initial description by Reed et al. (3) in 1975, minimal deviation melanoma (MDM) has received very little attention in the surgical literature. In the pathology literature, however, much attention was paid to MDM in the 1980s, as pathologists struggled with the characterization of melanomas, in search of a diagnosis other than melanoma that would reflect the more indolent nature of MDMs and not necessitate radical surgery. This was especially important given that these tumours occur in younger patients. In a recent study conducted at our institution, each patient with melanoma between January 1997 and May 2000 was retrospectively reviewed to determine those with a primary diagnosis of minimal deviation melanoma. Chart review revealed data regarding demographics, tumour size, tumour location, depth of invasion, occurrence of known metastatic disease, and any additional procedures undertaken (i.e.
c 2002 ELSEVIER SCIENCE LTD. ALL RIGHTS RESERVED. 0305-7372/02/$ - see front matter s
220
lymphatic mapping). The results were tabulated and compared with previously published data. A total of 1730 patients were identified as having melanoma. Thirty-one (1.7%) of these patients had MDM as their primary diagnosis. Fifty-eight percent (n ¼ 18) were in women while 43% (n ¼ 13) were found in men. The mean age was 26.6 years (range 9–69 years). Dimensions range from 4 to 17 mm in diameter. All lesions were ClarkeÕs level IV, with Breslow thickness ranging from 0.6 to 2.5 mm (mean 1.38 mm). Subtypes seen were Spitz (n ¼ 8), halo (n ¼ 6), spindle (n ¼ 4), spindle/epithelioid (n ¼ 4), dermal (n ¼ 3), naevoid (n ¼ 2), and desmoplastic (n ¼ 1). No subtype was identified in 3 patients. Locations included back (n ¼ 8), leg (n ¼ 7), arm/ shoulder (n ¼ 5), face (n ¼ 4), foot (n ¼ 3), scalp (n ¼ 2), chest/abdomen (n ¼ 2), and posterior neck (n ¼ 1). A single patient had two lesions. Five patients underwent sentinel lymph node mapping with metastatic melanoma found in a single node in just one patient. Originally MDM was thought to occur in the fourth and fifth decades of life, our results are significant because in our experience, the largest to date, the mean age is more than 14 years younger than previously described. MDMs fall somewhere on the continuum between benign nevi and frank melanomas. This ‘‘Common Final Pathway’’ theory, asserting that malignant melanomas arise from preexisting benign lesions, was first proposed in 1987. This is supported by evidence of MDM remnants or other less invasive pathology at the borders of melanomas and the
Y. D. PODNOS ET AL.
similarity of immunologic markers between MDM and malignant melanoma (4). Even within MDM, subtypes as seen in this study population occur that are named according to the types of benign nevus cells seen on the outside borders. In the progression from benign naevomelanocytic lesion to malignant melanoma, a logical, stepwise chain of events has been postulated (1). First, nevus cells appear at the apexes of rete ridges, from which they descend into the dermis. During this process, there is a loss of junctional and dermal components, leaving only naevomelanocytic components. As increasing atypia occurs, the cells lose their dendrites and less melanin is seen in the cytoplasm. Their shape changes from polygonal to round and, at this point, there is a transition from Type A to Type B naevomelanocytes. As they invade the reticular dermis, elongate, and proliferate, they become Type C naevomelanocytes. By definition, MDMs must have invasion into the reticular dermis (Clarke level IV). As compared to melanoma, they have less cellular atypia in the vertical growth element. Melanomas are notorious for having more cellular pleomorphism, increased mitotic activity, and larger nuclear to cytoplasmic ratios. Additionally, melanomas show less maturation and can infiltrate deeper dermal layers as single cells. MDM invades as broad fascicles (Figs. 1 and 2) (1). In contrast to malignant melanoma, in which the risks of metastasis include thickness, microscopic 2 satellitosis, and >6 mitoses=mm , the metastatic potential of MDM is still unknown. Several case reports
Figure 1 The epidermis is mildly atrophic without a significant junctional component. No pagetoid foci are present. There is no remarkable maturation identified within the dermal component (H&E, X100).
MINIMAL DEVIATION MELANOMA
221
Figure 2 Higher magnification exhibiting round nevic-type cells with some pleomorphism and small nuclei (H&E, X200).
of a primary MDM lesion with metastatic melanoma have been reported. The single positive lymph node mapping in our sample also showed melanoma in the node. These cases illustrate the concept of a ‘‘final common pathway’’ in melanoma genesis in that the bulk of the tumour was MDM while other parts that became metastatic could have already evolved into melanoma. Despite the ‘‘final common pathway’’ theory, MDM remains a less virulent neoplasm. Phillips et al. (1) examined 18 patients with MDM with only 2 (11%) dying from metastatic disease over a mean follow up period of 57 months. It is not known if the metastatic lesions were MDM or frank melanoma. In 8 patients presented by Barr et al. (5), there was no recurrence or mortality over a mean 16-month follow up. Our sample, though small, further confirms the lower incidence of metastasis in MDM. Therapy of MDM has been controversial ever since its description in 1975. Originally, pathologists did not want to label these lesions as melanomas, fearing radical operations and an adverse psychological response to the diagnosis by patients. With time, however, it became clear that because MDM is more indolent in nature, less invasive operations were warranted. In our experience, lymph node mapping was successful and sufficient in picking up the single metastatic lesion. One possible ex-
ception, however, are head and neck MDMs. Because of the rich vascular and lymphatic networks in those areas, a hypothetical increase in metastasis could occur (6). Clearly, further, more detailed evaluation of MDM is needed, particularly the determination of risk factors for MDM metastasis. Additionally, basic laboratory research to delineate more accurately the patholgical spectrum of benign naevi through to malignant melanoma is required.
REFERENCES 1. Phillips ME, Margolis RJ, Merot Y, et al. The spectrum of minimal deviation melanomas: a clinicopathologic study of 21 cases. Hum Path 1986; 17: 796–806. 2. Reed RJ. Minimal deviation melanoma. Hum Path 1990; 21: 1206–1211. 3. Reed RJ, Ichinose H, Clarke WH, et al. Common and uncommon melanocytic nevi and borderline melanomas. Semin Oncol 1975; 2: 119–147. 4. Reed RJ. The histologic variance of malignant melanoma: the interrelationship of histologic subtype, neoplastic progression, and biologic behavior. Pathology 1985; 17: 301–312. 5. Barr LH, Goldman LI, Solomon JA, et al. Minimal deviation melanomas. Surg Gyn Obstet 1984; 159: 546–548. 6. Becker DW, Miller CJ, Keller HB. Metastatic minimal deviation melanoma. Ann Plast Surg 1979; 4: 230–237.