Melanomas are a wide range of tumors that differ in their epidemiology, morphology, genetic profile, and biological behavior. They can be grouped as superficial spreading melanoma, lentigo maligna, and nodular melanoma. Reflectance confocal microscopy is useful for the evaluation of skin lesions that are dermoscopically doubtful by increasing diagnostic accuracy and specificity. This article provides a comprehensive overview of the different confocal main morphologies of distinct melanoma types as a function of the anatomic location of the tumor.
Key points
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The melanoma family encompasses a wide range of tumors that differ in their epidemiology, morphology, genetic profile, and biological behavior. According to histologic classification, melanomas can be grouped as superficial spreading melanoma (SSM), lentigo maligna (LM), and nodular melanoma (NM).
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On reflectance confocal microscopy, SSM typically shows the presence of atypical melanocytes with rounded, large body cells that are arranged in pagetoid fashion.
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LM is typified by the presence of dendritic melanocytes that are preferentially located around and along the adnexal openings.
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The hallmark of NM is represented by the presence of the so-called cerebriform nests that are solid and dark aggregates of melanocytes demarcated by bright fibrous collagen bundles.
Introduction
Reflectance confocal microscopy (RCM) is recognized as a useful tool for the evaluation of skin lesions that are dermoscopically doubtful by increasing diagnostic accuracy and specificity. However, this level of improvement is contingent on gaining expertise in its use as per any technology (ie, reading computed tomography [CT] scan or MRI). Although, the use of RCM has been mainly to help clinicians in detecting more melanomas at an early stage, it is useful to reduce the number of unnecessary biopsies of benign lesions that might be dermoscopically regarded as melanoma simulators. This, in turn, results in an improved malignant biopsy to benign biopsy ratio. In fact, a main challenge in dermato-oncology remains differentiating atypical nevi from melanoma. To accomplish this task, it is important to recognize the benign patterns commonly seen in nevi that are overwhelmingly present compared with melanoma. Several studies have demonstrated that melanocytic nevi tend to manifest 1 or 2 benign architectural patterns that exhibit symmetry in their silhouette and the absence or paucity of cytologic atypia. Conversely, melanomas tend to manifest architectures that deviate from the benign nevus patterns. In fact, melanomas manifest a wide range of confocal features and these are obviously linked to specific factors such as the histopathological subtype, anatomic location, tumor thickness, and possibly even the specific genetic mutations carried by the tumor. Thus, it is intuitively obvious that melanoma may express a variable combination of RCM features that can be theoretically infinite. With that said, what many melanomas have in common is that they deviate from the benign nevus pattern and they often reveal at least 1 or 2 of the melanoma-specific structures summarized in Table 1 . RCM is not currently explored in vivo for the diagnosis of acral melanomas and nail melanoma because of the intrinsic limitation of the device.
| RCM Criterion | Definition | |
|---|---|---|
| Epidermis | Pagetoid cells | Pagetoid cells are considered when large nucleated cells, twice the size of keratinocytes, with a dark nucleus and bright cytoplasm, are observable within superficial layers. They can be differentiated based on the shape (roundish, dendritic, or pleomorphic) when both shapes are present. Pagetoid cells, especially the roundish ones, represent the most accurate pattern for melanoma diagnosis. |
| Broadened honeycombed pattern | Broadened honeycombed corresponds to a honeycombed pattern with bright enlarged and broadened intercellular spaces, frequently observable in nodular lesions, such as nodular melanomas and nodular nonmelanocytic skin cancers. | |
| Irregular keratinocytes | The overall epidermal pattern is constituted by irregular keratinocytes when irregularity in size of the cells and thickness of the contour are present. | |
| Disarranged pattern | It is characterized by disarray of the normal architecture of the superficial layers with unevenly distributed bright granular particles and cells, in the absence of honeycombed or cobblestone pattern. | |
| Dermoepidermal junction | Atypical cells | Atypical cells correspond to irregular in size, shape, and reflectivity, round to oval or stellate cells, occasionally with branching dendritic structures. They show a bright cytoplasm with clearly outlined borders and sharply contrasted dark nucleus inside. |
| Nonspecific pattern at dermoepidermal junctional | A nonuniform architecture constituted by unevenly distributed dermal papillae, irregular in size and shape, usually without a demarcated rim of bright cells (nonedged papillae), and separated by series of large reflecting cells, is typically observed in melanomas. | |
| Nonedged papillae | Dermal papillae usually show a not clearly outlined contour, without a demarcated rim of bright cells but separated by a series of large reflecting cells or by nondiscrete aggregates of melanocytes at the dermoepidermal junction. | |
| Upper Dermis | Atypical cells within the papillae | Single nucleated cells correspond to round to oval, not aggregated cells, with well-demarcated refractive cytoplasm and well-demarcated dark nucleus infiltrating dermal papilla. |
| Atypical dense and sparse nests | Dense and sparse nests constituted by aggregates of pleomorphic cells, nonhomogeneous in size, shape, and reflectivity, observable in melanomas. | |
| Cerebriform nests | Cerebriform clusters correspond to cellular clusters consisting of confluent amorphous aggregates of low-reflecting cells exhibiting granular cytoplasm without evident nuclei and ill-defined borders, being the aggregates brain-like in appearance, showing a fine hyporeflective fissure-like appearance. Although their observation is infrequent, cerebriform nests are specific for invasive melanomas and they are usually located within the nodular component of the tumor. | |
| Inflammation | Plump bright cells are described as plump, irregular, bright cells with ill-defined borders and usually no visible nucleus. Sometimes they are crowded within the papilla. Bright spots and small bright particles are small cells with very bright hyper-reflecting cytoplasm, sometimes visible nuclei, corresponding to leukocyte infiltration. | |
| Fibrosis | Fibrosis is composed by coarse collagen structures which appear as an amorphous fibrillary material. Their distribution could be reticulated, forming coarse web-like structures in the dermis, or in bundles, gathered into large fasciae. |
Furthermore, there still remain melanomas that are featureless on dermoscopy and RCM. To not miss these lesions, careful periodic digital dermoscopic surveillance should be always considered.
This article provides a comprehensive overview of the different confocal main morphologies of distinct melanoma types as a function of the anatomic location of the tumor.
Introduction
Reflectance confocal microscopy (RCM) is recognized as a useful tool for the evaluation of skin lesions that are dermoscopically doubtful by increasing diagnostic accuracy and specificity. However, this level of improvement is contingent on gaining expertise in its use as per any technology (ie, reading computed tomography [CT] scan or MRI). Although, the use of RCM has been mainly to help clinicians in detecting more melanomas at an early stage, it is useful to reduce the number of unnecessary biopsies of benign lesions that might be dermoscopically regarded as melanoma simulators. This, in turn, results in an improved malignant biopsy to benign biopsy ratio. In fact, a main challenge in dermato-oncology remains differentiating atypical nevi from melanoma. To accomplish this task, it is important to recognize the benign patterns commonly seen in nevi that are overwhelmingly present compared with melanoma. Several studies have demonstrated that melanocytic nevi tend to manifest 1 or 2 benign architectural patterns that exhibit symmetry in their silhouette and the absence or paucity of cytologic atypia. Conversely, melanomas tend to manifest architectures that deviate from the benign nevus patterns. In fact, melanomas manifest a wide range of confocal features and these are obviously linked to specific factors such as the histopathological subtype, anatomic location, tumor thickness, and possibly even the specific genetic mutations carried by the tumor. Thus, it is intuitively obvious that melanoma may express a variable combination of RCM features that can be theoretically infinite. With that said, what many melanomas have in common is that they deviate from the benign nevus pattern and they often reveal at least 1 or 2 of the melanoma-specific structures summarized in Table 1 . RCM is not currently explored in vivo for the diagnosis of acral melanomas and nail melanoma because of the intrinsic limitation of the device.
| RCM Criterion | Definition | |
|---|---|---|
| Epidermis | Pagetoid cells | Pagetoid cells are considered when large nucleated cells, twice the size of keratinocytes, with a dark nucleus and bright cytoplasm, are observable within superficial layers. They can be differentiated based on the shape (roundish, dendritic, or pleomorphic) when both shapes are present. Pagetoid cells, especially the roundish ones, represent the most accurate pattern for melanoma diagnosis. |
| Broadened honeycombed pattern | Broadened honeycombed corresponds to a honeycombed pattern with bright enlarged and broadened intercellular spaces, frequently observable in nodular lesions, such as nodular melanomas and nodular nonmelanocytic skin cancers. | |
| Irregular keratinocytes | The overall epidermal pattern is constituted by irregular keratinocytes when irregularity in size of the cells and thickness of the contour are present. | |
| Disarranged pattern | It is characterized by disarray of the normal architecture of the superficial layers with unevenly distributed bright granular particles and cells, in the absence of honeycombed or cobblestone pattern. | |
| Dermoepidermal junction | Atypical cells | Atypical cells correspond to irregular in size, shape, and reflectivity, round to oval or stellate cells, occasionally with branching dendritic structures. They show a bright cytoplasm with clearly outlined borders and sharply contrasted dark nucleus inside. |
| Nonspecific pattern at dermoepidermal junctional | A nonuniform architecture constituted by unevenly distributed dermal papillae, irregular in size and shape, usually without a demarcated rim of bright cells (nonedged papillae), and separated by series of large reflecting cells, is typically observed in melanomas. | |
| Nonedged papillae | Dermal papillae usually show a not clearly outlined contour, without a demarcated rim of bright cells but separated by a series of large reflecting cells or by nondiscrete aggregates of melanocytes at the dermoepidermal junction. | |
| Upper Dermis | Atypical cells within the papillae | Single nucleated cells correspond to round to oval, not aggregated cells, with well-demarcated refractive cytoplasm and well-demarcated dark nucleus infiltrating dermal papilla. |
| Atypical dense and sparse nests | Dense and sparse nests constituted by aggregates of pleomorphic cells, nonhomogeneous in size, shape, and reflectivity, observable in melanomas. | |
| Cerebriform nests | Cerebriform clusters correspond to cellular clusters consisting of confluent amorphous aggregates of low-reflecting cells exhibiting granular cytoplasm without evident nuclei and ill-defined borders, being the aggregates brain-like in appearance, showing a fine hyporeflective fissure-like appearance. Although their observation is infrequent, cerebriform nests are specific for invasive melanomas and they are usually located within the nodular component of the tumor. | |
| Inflammation | Plump bright cells are described as plump, irregular, bright cells with ill-defined borders and usually no visible nucleus. Sometimes they are crowded within the papilla. Bright spots and small bright particles are small cells with very bright hyper-reflecting cytoplasm, sometimes visible nuclei, corresponding to leukocyte infiltration. | |
| Fibrosis | Fibrosis is composed by coarse collagen structures which appear as an amorphous fibrillary material. Their distribution could be reticulated, forming coarse web-like structures in the dermis, or in bundles, gathered into large fasciae. |
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Shining into the White
Application of Handheld Confocal Microscopy for Skin Cancer Diagnosis
The Role of Reflectance Confocal Microscopy in Clinical Trials for Tumor Monitoring
Fluorescence (Multiwave) Confocal Microscopy
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