Can Melan-A replace S-100 and HMB-45 in the evaluation of sentinel lymph nodes from patients with malignant melanoma?

The sentinel lymph node (SLN) biopsy has become an increasingly important procedure used in the primary staging of malignant melanoma. However, micrometastases in a lymph node can be easily missed on routine H&E-stained sections. Therefore, S-100 and HMB-45 IHC stains are standardly performed on grossly negative SLNs for detection of metastatic melanoma. Each of these IHC markers, however, is not ideal. The authors investigated whether the newer IHC marker Melan-A would improve the detection of metastatic melanoma in SLN biopsies. Forty lymph nodes previously diagnosed with metastatic melanoma were retrospectively evaluated for S-100, HMB-45, and Melan-A expression. In addition, 42 SLN biopsies for metastatic melanoma detection were prospectively collected and evaluated for S-100, HMB-45, and Melan-A expression. All lymph nodes with metastatic melanoma from the retrospective study demonstrated S-100 reactivity. Five of the lymph nodes with metastatic melanoma from the retrospective study failed to express either HMB-45 or Melan-A, all of which displayed a desmoplastic morphology. One of the metastases positive for S-100 and HMB-45 failed to show reactivity with Melan-A (3%). The prospective study found 10 lymph nodes from 42 cases to be positive for metastatic melanoma, which were positive for S-100 (100%). Nine of the involved lymph nodes were positive for HMB-45(90%), and nine were positive for Melan-A (90%). Melan-A, although very specific, cannot replace the use of S-100 and HMB-45 for the detection of metastatic melanoma in SLNs. It can, however, substitute for HMB-45 with equally good results.

Nephrogenic fibrosing dermopathy/nephrogenic systemic fibrosis with diaphragmatic involvement in a patient with respiratory failure.

Nephrogenic fibrosing dermopathy/nephrogenic systemic fibrosis (NFD/NSF) is a disorder occurring exclusively in patients with renal disease. Until recently, it has been considered a fibrosing disorder essentially confined to the skin and underlying superficial soft tissue. Recent reports, however, have described patients with involvement of other organ systems, suggesting that this disorder is actually a systemic disease with preferential cutaneous manifestations. We describe a patient with end-stage renal disease with diagnosed NFD/NSF who subsequently developed respiratory failure leading to his death. Autopsy findings showed NFD/NSF involving the skin of all extremities, as well as diffuse diaphragm involvement.

Mechanisms of chemical cooperative carcinogenesis by epidermal Langerhans cells.

Cutaneous squamous cell carcinoma (SCC) is the most prevalent invasive malignancy with metastatic potential. The epidermis is exposed to a variety of environmental DNA-damaging chemicals, principal among which are polyaromatic hydrocarbons (PAHs) ubiquitous in the environment, tobacco smoke, and broiled meats. Langerhans cells (LCs) comprise a network of dendritic cells situated adjacent to basal, suprabasal, and follicular infundibular keratinocytes that when mutated can give rise to SCC, and LC-intact mice are markedly more susceptible than LC-deficient mice to chemical carcinogenesis provoked by initiation with the model PAH, 7,12-dimethylbenz[a]anthracene (DMBA). LCs rapidly internalize and accumulate DMBA as numerous membrane-independent cytoplasmic foci. Repopulation of LC-deficient mice using fetal liver LC-precursors restores DMBA-induced tumor susceptibility. LC expression of p450 enzyme CYP1B1 is required for maximal rapid induction of DNA-damage within adjacent keratinocytes and their efficient neoplastic transformation; however, effects of tumor progression also attributable to the presence of LC were revealed as CYP1B1 independent. Thus, LCs make multifaceted contributions to cutaneous carcinogenesis, including via the handling and metabolism of chemical mutagens. Such findings suggest a cooperative carcinogenesis role for myeloid-derived cells resident within cancer susceptible epithelial tissues principally by influencing early events in malignant transformation.

Epithelioid fibrous papule - a new variant.

Fibrous papules (FPs) are common benign lesions occurring most frequently on the nose. Multiple variants have been described, including classic, hypercellular, clear cell, pigmented, pleomorphic, inflammatory and granular FPs. We describe a group of FPs with characteristics that do not easily fit into any of the above categories, with diffuse sheets of distinctive epithelioid cells, causing potential diagnostic confusion. Immunoperoxidase stains show that the cells of this 'epithelioid fibrous papule' are reactive for procollagen, and are negative for NKI/C3, unlike previously described clear cell variants.

Histopathologic comparison of nephrogenic fibrosing dermopathy and scleromyxedema.

BACKGROUND: Nephrogenic fibrosing dermopathy (NFD) clinically presents as indurated plaques and papules in patients with renal dysfunction. The differential diagnosis generally includes scleromyxedema (SMX), an idiopathic systemic disorder with cutaneous manifestations, in which patients also develop indurated papules and plaques. The two entities can be extremely difficult to distinguish microscopically. Histopathologic differences with immunophenotypic comparison, to our knowledge, have not been thoroughly studied. We compared these two entities with an emphasis on immunohistochemistry. DESIGN: Nine biopsies diagnosed as NFD and seven biopsies diagnosed as SMX were retrospectively collected from the University of Pennsylvania Medical Center's surgical pathology and dermatopathology archives. Immunohistochemical staining for CD34, factor XIIIa, CD31, smooth muscle actin, CD68, and procollagen-I, as well as colloidal iron, were performed on each biopsy. Amount of expression for each of these markers, as well as degree of inflammation, for each biopsy was evaluated using a grading system of 0--3. RESULTS: Overall, NFD and SMX showed similar expression for all markers except procollagen-I, which showed increased expression in SMX. DISCUSSION: Although some immunophenotypic differences were found, our study did not demonstrate microscopic characteristics that can be easily used diagnostically to distinguish NFD from SMX. Clinical pathologic correlation is paramount in distinguishing these two entities. Kucher C, Xu X, Pasha T, Elenitsas R. Histopathologic comparison of nephrogenic fibrosing dermopathy and scleromyxedema.

Expression of Melan-A and Ki-67 in desmoplastic melanoma and desmoplastic nevi.

BACKGROUND: Desmoplastic melanoma (DMM) is an uncommon melanoma variant with a distinct morphology, including a prominent spindle cell component with fibrosis, as well as a distinct immunohistochemical profile. Histologically, the spindle cell component of DMM can be confused with sclerotic/desmoplastic nevi, nonpigmented blue nevi, scar, and neural tumors. The histological distinction between sclerotic/desmoplastic/blue nevi and DMM using standard light microscopic techniques can be exceedingly subtle. Therefore, we investigated whether immunohistochemical staining for Melan-A and Ki-67 expression can be used to discriminate these lesions, distinguishing between epithelioid and spindle cell compartments of the lesions. DESIGN: Fifty cases of DMM and 13 cases of sclerotic/desmoplastic/blue nevi were identified. Standard immunohistochemical techniques were used with antibodies towards HMB-45, Melan-A (A103), and Ki-67; 43 of 50 DMM cases were available for staining with Melan-A, 42 of 50 for HMB-45, and 31 of 50 cases were stained with Ki-67. All 13 nevi were stained for Melan-A and 8 for Ki-67. Immunoreactivity to Ki-67 antibody was scored as 0 to 5%, 6 to 10%, 11 to 30%, or greater than 30% positive tumor cells. RESULTS: Only 3 of 43 and 3 of 42 of spindle cell compartments of DMMs were positive for Melan-A and HMB-45, respectively. Focal staining of epithelioid cells in the junctional component or superficial dermis was observed in 33% (14/43). In contrast, 100% of the 13 nevi were strongly positive for Melan-A (P < 0.001). Seventeen melanomas (55%) were 0 to 5% positive for Ki-67, five (16%) fell into the 6 to 10% category, three (10%) were between 11 and 30%, and six (19%) were at least focally greater than 30% positive. All 8 nevi (100%) had less than 5% positive cells for Ki-67 (P = 0.02), with only 2 cases having more than 2% positive cells. CONCLUSION: The sclerotic/desmoplastic and hypopigmented blue nevi were uniformly positive for Melan-A, while the vast majority of DMM were negative in their spindle cell compartments. Melan-A is very useful in distinguishing between DMM and sclerotic nevi. Ki-67 appears to be an inconsistent marker for DMM. However, a high labeling index (over 5%) may be used as a clue in diagnosing DMM.