Myxoid atypical fibroxanthoma: a previously undescribed variant.

BACKGROUND: Atypical fibroxanthomas (AFX) are dermal-based cutaneous tumors typically found in sun-damaged skin of the elderly. Histologic variants include spindle cell, clear cell, osteoid, osteoclastic, chondroid, pigmented, and granular cell. To date, myxoid change in AFX, has not been described. METHODS: Four cases were retrieved from the consultation and surgical pathology files of Knoxville Dermatopathology Laboratory, Knoxville, Tennessee during a 4-year period. The clinical and histologic findings were reviewed and Alcian blue/periodic acid-Schiff (PAS) stain and panel of immunohistochemical stains was obtained. RESULTS: All 4 lesions occurred as solitary lesions in elderly males on the head and neck (2 cases) and upper extremity (2 cases). Histologically all tumors demonstrated a well-circumscribed, cellular lesion centered in the dermis and composed of a mix of atypical pleomorphic and spindle cells in a prominent myxomatous background. A junctional component was absent and the tumors did not arise from the epidermis or adnexal structures. Subcutaneous involvement was absent in all cases. Tumor cells were negative for melanocytic and epithelial markers. Positive staining was noted with CD10 (3/4 cases) and vimentin (4/4 cases). CONCLUSION: Myxoid change in AFX is rare and previously undescribed in the English literature. Myxoid change may be a prominent finding in benign and malignant cutaneous tumors and awareness of this variant of AFX will avoid misdiagnosis.

Primary invasive melanoma and basal cell carcinoma (collision tumor) with blue nevus-like cutaneous metastases.

The simultaneous presence of two disparate neoplasms occurring in the same specimen has been well documented, albeit uncommonly. The juxtaposition of malignant melanoma and basal cell carcinoma (BCC) has been rarely reported in case reports, with most cases describing melanoma in situ and BCC. We present two cases of invasive melanoma (Clark level IV, no microscopic satellites present) intimately associated with BCC, and in areas distinction of the two lesions was difficult. Immunohistochemical studies delineated the two cell populations. In addition, one patient presented with multiple cutaneous metastases, all simulating blue nevi. The metastases occurred in the same anatomical region as the primary tumor, and histologically consisted of pigmented dendritic melanocytes and melanophages in the superficial and mid-dermis and arranged in a blue nevus-like lesion. Histologic clues suggesting the possibility of a metastatic melanoma included a sparse lymphocytic infiltrate, the presence of an epithelioid component and atypia of the dendritic melanocytes. However, without appropriate clinical history, the lesions could be overlooked as ordinary blue nevus. Collision tumors containing invasive melanoma and BCC are rare and this is the first report of a collision tumor with blue nevus-like metastasis. Awareness of this phenomenon and pattern of metastasis, together with the clinical findings will aid in the correct classification of these lesions.

Herpesvirus infection of seborrheic keratoses.

We present three examples of patients with seborrheic keratoses complicated by necrotizing herpesvirus infection. Two patients had localized cutaneous herpetic infections, and the third patient had a generalized cutaneous herpesvirus infection. Two of the lesions were thought to be squamous cell carcinoma. The third was clinically identified as inflamed seborrheic keratosis. Herpesvirus infection was not clinically suspected in two of the patients. The histologic changes were similar in all cases. Epidermal proliferation was accompanied by hyperkeratosis and pseudo horn cyst formation. Extensive keratinocyte necrosis was present along with balloon degeneration of keratinocytes, herpetic viral inclusions, and multinucleated giant cells. Viral lesions of molluscum contagiosum and human papillomavirus have been observed in benign skin proliferations. Nevertheless, we were unable to find descriptions of herpesvirus involvement in seborrheic keratosis in a Medline search. Necrotic seborrheic keratoses should be carefully examined for the possibility of herpesvirus infection, a condition that may be improved by prompt medical intervention as demonstrated in one of our cases.

Microphthalmia transcription factor expression in cutaneous benign, malignant melanocytic, and nonmelanocytic tumors.

The protein encoded by the microphthalmia (mi) gene is a transcription factor essential for the development and survival of melanocytes. Using a monoclonal antibody generated against human Mi transcription factor protein (Mitf) the authors previously demonstrated that Mitf expression is conserved in primary and metastatic malignant melanomas, and appears to be a highly sensitive and specific melanocytic marker. Mitf expression in various cutaneous nevi and cutaneous nonmelanocytic tumors has not been documented systematically. The authors evaluated Mitf immunostaining in 62 benign nevi, 58 primary cutaneous melanomas, and 53 nonmelanocytic tumors. Mitf immunostaining was conserved in all benign nevi, with Spitz nevi and neurotized nevi demonstrating decreased staining intensity. With the exception of desmoplastic melanomas, all primary cutaneous melanomas were immunopositive regardless of the cell type. Only one of 14 desmoplastic melanomas was Mitf positive. None of the nonmelanocytic tumors was immunopositive, including those lesions that may resemble melanoma histologically (spindle cell carcinomas, atypical fibroxanthomas, and leiomyosarcomas). The results demonstrate that Mitf antibody expression is conserved in the majority of benign and malignant melanocytic lesions, and that it may be helpful in the diagnosis of primary melanocytic skin lesions. Its use in desmoplastic melanomas is limited and is reflective of other melanocyte-associated antigens. Mitf discriminates between spindle cell nonmelanocytic tumors and melanomas with a spindle cell morphology, and is useful in a panel with other appropriate antibodies.

Possible role of cellular immunity: a case of cellulitis.

On the basis of the observation that there was a "skip" area in an otherwise diffuse drug eruption where cellulitis had previously occurred, it is theorized that both delayed hypersensitivity type of dermatologic drug reaction and cellulitis share pathogenic mechanisms.

Giant-sized condyloma of the breast with focal acantholytic changes.

BACKGROUND: A healthy 26-year-old pregnant woman presented with a 6.0-cm exophytic mass in her left inframammary fold. The lesion was surgically excised. METHODS: Histopathologic sections of the skin lesion were reviewed in hematoxylin and eosin-stained slides. Additional sections were studied by an in situ hybridization method for human papillomavirus DNA (HPV) types 6 and 11. RESULTS: The histopathologic examination demonstrated a benign exophytic, verrucous and papillary epidermal proliferation with features of condyloma acuminatum. Reactivity to HPV DNA types 6 and 11 was demonstrated by in situ hybridization method. The epidermis adjacent to, and focally within, the neoplasm showed multiple areas of suprabasilar and intraepidermal acantholysis without dyskeratosis. CONCLUSIONS: Condylomas related to HPV 6 and 11 may be found in extragenital locations including conjunctiva, oral and nasal mucosa. To our knowledge, however, the extragenital condylomas described in the literature have not included the giant-sized variant. We describe an example of a benign, giant-sized condyloma acuminatum of the breast with nearby acantholytic alterations similar to Hailey-Hailey disease.

Thin melanomas.

Thin melanoma refers to that grouping of melanomas that statistically have a good prognosis and survival rate. A small but significant percentage of these lesions metastasize and cause mortality. Histologically, these lesions comprise a diverse grouping of tumors of any intraepidermal growth pattern; in the radial or vertical growth phase; or in anatomic level I, II, III, or IV. Additional histologic findings may also be variably present, such as regression, tumor infiltrating lymphocytes, and mitoses. Molecular studies suggest that thin melanomas may have different properties to thicker and metastatic melanomas. The factors governing the ability of thin melanomas to metastasize and cause mortality are not known. Certain histologic and molecular parameters, some of which have been alluded to previously, may provide clues to understanding the parameters governing the aggressive nature of some of these lesions. Further research is required to enhance our understanding of thin melanomas.

Biopsy specimen findings in patients with previous lower extremity cellulitis after saphenous venectomy for coronary artery bypass graft surgery.

BACKGROUND: No previous study has examined the immune and inflammatory mechanisms involved in the pathogenesis of lower extremity cellulitis after saphenous venectomy for coronary artery bypass graft surgery. OBJECTIVE: Our purpose was to determine the histopathologic, immunologic, and inflammatory findings in skin biopsy specimens from saphenous venectomy limbs of patients with previous bouts of cellulitis. METHODS: Biopsy specimens were obtained from five patients with previous episodes of cellulitis. Specimens of the contralateral lower extremity of each patient were obtained for controlled comparisons. RESULTS: Histopathologic findings did not provide evidence that could account for the tendency for cellulitis to develop. Moreover, the distribution of CD1a, HLA-DR, intercellular adhesion molecule-1, and lymphocyte function-associated antigen type 1 were similar in specimens from the postvenectomy and contralateral legs. No tumor necrosis factor-alpha expression was found in specimens from the lower extremities. CONCLUSION: The mechanisms responsible for the production of this disorder do not involve the mediators studied.

Cutaneous leiomyomas lack estrogen and progesterone receptor immunoreactivity.

Gonadotropin-releasing hormone analog therapy is useful in treating uterine and some extrauterine smooth muscle tumors. These smooth muscle tumors have been demonstrated to have estrogen receptor and progesterone receptor immunoreactivity. The estrogen receptor and progesterone receptor immunoreactivity of smooth muscle tumors of the skin has not been reported. We evaluated 15 examples of cutaneous leiomyomas for estrogen receptor and progesterone receptor with ER-1D5 antibody and PGR-1A6 antibody. None of the 15 cutaneous leiomyomas demonstrated positive staining by this method. The tumorigenesis of cutaneous leiomyomas does not appear to be related to estrogen or progesterone receptor-mediated effects.

Anticytokeratin antibody 34 beta E12 staining in prostate carcinoma.

Anticytokeratin antibody 34 beta E12 is advocated as an immunohistochemical stain for discriminating benign and malignant lesions of the prostate. Positive staining with 34 beta E12 is said to identify benign lesions, whereas negative staining is said to help substantiate a diagnosis of carcinoma. It is further claimed that 34 beta E12 does not stain prostate carcinoma. The studies leading to these conclusions used hematoxylin-eosin-stained sections of primary prostate lesions as controls. Although the cytokeratin content of a few cell lines of metastatic prostate carcinoma has been investigated, the 34 beta E12 immunohistochemical staining of metastatic prostate carcinoma has not been evaluated. If 34 beta E12 positivity is present only in benign prostate cells, then metastatic prostate carcinoma cells should be uniformly negative with this stain. In 14 cases of moderate and high-grade prostate cancer with metastases to lymph nodes, we found 34 beta E12 positivity in 6 (43%) of 14 metastases and in 7 (54%) of 13 primary tumors. Our findings of 34 beta E12 staining in primary and metastatic moderately and poorly differentiated prostate carcinoma differ from those reported in the literature for well-differentiated prostate carcinoma. We urge caution in the use and interpretation of 34 beta E12 staining for the diagnosis of primary and metastatic prostate carcinoma.

Mucinous differentiation in adnexal sweat gland tumors.

We report an eccrine acrospiroma, on the cheek of a 29-year-old female, in which the presence of abundant mucinous (goblet cell) metaplasia closely mimicked a primary mucoepidermoid carcinoma. To determine the frequency of mucinous differentiation in benign adnexal sweat gland tumors, we evaluated sixty-five cases in hematoxylin and eosin stained sections for the presence of goblet cells and sixty of these for mucicarmine positivity. Goblet cell metaplasia was seen in 3 of 12 acrospiromas, 1 of 8 mixed tumors, and in 1 of 9 cases of syringocystadenoma papilliferum. All goblet cells were positive for mucicarmine, except in one case of acrospiroma, where goblet cells were not detected on the section stained with mucicarmine. In addition, intracellular mucin, inclusive of goblet cells, was seen in 5 of 12 acrospiromas, 1 of 11 poromas, 5 of 8 mixed tumors, 3 of 13 spiradenomas, 1 of 5 cylindromas, 3 of 9 cases of syringocystadenoma papilliferum and 1 of 3 nipple adenomas. The majority of the tumors had both extracellular mucicarmine positivity (40 of 60) and luminal mucicarmine positivity (39 of 60). We conclude that mucinous differentiation in sweat gland tumors, as defined by the presence of goblet cells and/or intracellular mucicarmine positivity, is common and does not indicate aggressive behavior. Mucinous differentiation in benign sweat gland tumors should not be confused with more aggressive mucoepidermoid carcinomas of salivary gland origin or adenosquamous carcinoma.

Anophthalmic socket pain.

We examined and treated four patients with anophthalmic socket pain. Conditions responsible for this problem in this series included scleritis after evisceration, amputation neuroma, pain from a skull-base meningioma, and chemical dependency with drug-seeking behavior. The pain associated with the scleritis after evisceration responded to removal of the scleral remnant. The pain associated with the amputation neuroma responded to removal of the orbital implant and its pseudocapsule in which the amputation neuroma was embedded. The pain associated with the meningioma was intractable. The pain associated with the chemical dependency remained a persistent problem. A careful history and physical examination are critical in the evaluation of anophthalmic socket pain. Computed tomography or magnetic resonance imaging may be helpful in some cases.

Intravenous glomus tumor of the forearm.

An intravenous glomus tumor occurring in a forearm vein is reported. The patient had a painful subcutaneous mass which was completely excised. This mass was a neoplasm which expanded the lumen of a vein and extended throughout its wall into the surrounding subcutaneous fat. The neoplasm consisted of sheets of rounded cells with a capillary stroma. The neoplastic cells were closely apposed to the capillary vessels and were positive for vimentin, smooth muscle actin and muscle specific actin. The cells were negative for desmin, factor VIII-related antigen, epithelial membrane antigen, cytokeratins, S-100 protein and chromogranin. This is the 2nd reported case of intravenous glomus tumor of the forearm. This unusual presentation may be due to intravascular extension by a cutaneous glomus tumor. The potential for intravascular growth by glomus tumor should be recognized by surgeons, dermatologists and pathologists.

Inflammatory abdominal aortic aneurysm and the associated T-cell reaction: a case study.

The immune response associated with an inflammatory abdominal aortic aneurysm was studied by determining the phenotypes of lymphocytes in the peripheral blood, the aortic aneurysm wall, and the perianeurysmal tissue. Increased numbers of activated T cells were found in all three areas. After aneurysm repair, peripheral blood analysis demonstrated normalization of the T-cell subsets. These data suggest that inflammatory abdominal aortic aneurysm is associated with a measurable immune response in peripheral blood with elevation of the same subset of inflammatory cells (CD4) as detected in abdominal aortic aneurysm tissue, and the immune response regresses after aneurysm repair.

Estrogen receptors in skin appendage tumors and extramammary Paget's disease.

Determination of estrogen receptors (ER) in breast carcinoma is valuable in the management of patients. However, little is known about the presence of these receptors in other tumors. Normal skin appendages and their neoplasms, including extramammary Paget's disease (EPD), might be expected to express ER since the breast is histogenetically related to sweat glands. In this study, 41 cases of skin appendage tumors (SAT) and 11 cases of EPD were stained using the ER-ICA monoclonal kit (Abbott, Chicago, IL) with a modified technique for paraffin-embedded sections. Controls included 10 biopsies of primary breast carcinoma and 4 cases of metastatic breast carcinoma to skin, all positive for ER. None of the samples of SAT or EPD showed staining for ER. Normal skin appendages were also negative. Normal vaginal epithelium in one case of EPD showed positive nuclear staining for ER. ER determination using immunohistochemical technique in paraffin-embedded sections may be useful in the differential diagnosis between malignant SAT and metastatic breast carcinoma in the skin. The absence of ER in normal skin appendages suggests that its apparition is a feature of specialized differentiation of breast epithelium.

Histopathological changes in leiomyomata treated with leuprolide acetate.

Several studies have shown a decrease in uterine and/or leiomyoma volume when treated with leuprolide acetate (LA), a widely used gonadotropin-releasing hormone agonist. The mechanism by which these changes occur is unknown. In this study, the histopathological slides of 31 women of reproductive age who underwent hysterectomy or myomectomy were blindly reviewed by a pathologist. Seventeen women underwent myomectomy. Among those, 10 were treated with LA. The tumors in all of these patients were reduced in size after therapy. Histopathologically, the LA treatment correlated with a significant reduction in cellularity. No significant change in fibrosis, edema, or mitotic activity was seen.

Application of immunohistochemistry in the differential diagnosis of skin tumors.

As with neoplasms in any tissue, skin tumors may be categorized as epithelial or mesenchymal, benign or malignant, and primary or metastatic. Immunoperoxidase stains are useful in elucidating the nature of the tumor cells, especially in poorly differentiated tumors. It is important to consider that tumors may exhibit staining patterns different from the typical or reported results. This may be because of intrinsic features of the neoplasm such as the aberrant expression of antigens (markers). Furthermore, the staining of the tumor may be affected by tissue preservation and fixation as well as by the selection of antibodies used for staining. For this reason, the pathologist should be vigilant in comparing the results of unknown tumors with standard controls, with results in the literature, and with his or her own experience. Unusual neoplasms may require additional tissue for analysis, study by other ancillary methods such as electron microscopy, or consultation by more experienced laboratories. These guidelines should be helpful in providing accurate diagnosis of skin tumors.