Lymphoscintigraphy in melanoma: initial evaluation of a low protein dose monoclonal antibody cocktail.

A low protein dose (73 +/- 10 micrograms total) 131I-labeled monoclonal antibody cocktail made of equal microgram quantities of 225.28S (IgG2a) and 763.24T (IgG1) murine monoclonal antibodies, which bind additively to a high molecular weight antigen of melanoma, was evaluated as a lymphoscintigraphic agent in 17 patients with intermediate to thick (mean Breslow depth, 3.39 +/- 0.64 mm) melanomas or clinical Stage II disease scheduled for nodal dissection. Eleven of the patients were clinically Stage I while 6 were clinically Stage II. 131I antibody cocktail, 258 +/- 10 microCi, was administered s.c. at the site of the primary melanoma or its scar following surgical removal. In eight patients, 63 +/- 8 microCi of 125I nonspecific normal sheep IgG was coadministered s.c. Gamma camera imaging was conducted beginning immediately after and continuing for several days following injection. Surgical resection, weighing, and gamma counting of the draining lymph nodes were undertaken in all patients. On gamma scans, early nodal uptake of antibody was most pronounced and of longest duration in the tumor pathologically positive patients (5 of 7 had visible nodal uptake, 4 of 7 visually stable or rising with time), with the t 1/2 of nodal clearance by gamma scan significantly (P less than 0.05) longer than in the negative patients in whom 4 of 10 showed some, although generally transient (0 of 10 stable or rising), nodal uptake. Scans were not easily interpretable when the injection site was very near the draining nodal group, in part due to the detection of scatter activity from the injection site. In several instances the scan was correct and the clinical examination was incorrect as regards nodal disease. Quantitative analysis of the surgically excised draining nodes showed significantly (P less than 0.001) more 131I anti-melanoma antibody uptake in the 21 tumor-involved nodes [0.01217% injected dose (ID)/node median] than in the 512 tumor-negative nodes (0.00051% ID/node median). Median percentage ID/g of anti-melanoma antibody in tumor-involved nodes was significantly greater (P less than 0.01) than in tumor-negative nodes (0.01984 versus 0.003215% ID/g). 125I-labeled nonspecific antibody did not accumulate significantly more in the tumor-involved nodes on a per node or per g basis in the 283 of 533 nodes studied using the dual-label approach (0.0036 versus 0.00092% ID/g). These data demonstrate that by external imaging and by tissue counting that a radiolabeled anti-melanoma monoclonal antibody cocktail can specifically accumulate to melanoma-involved lymph nodes following s.c. administration.(ABSTRACT TRUNCATED AT 400 WORDS)

Cutaneous lymphadenoma.

Thirteen cases of a unique cutaneous tumor are presented. The lesions presented as single, nondescript, skin-color nodules. Eleven were located on the head and two were on the legs. The male/female ratio was 8:5. The age at diagnosis ranged between 21 and 55 years (mean: 39). The duration of the lesions was from several months to more than 20 years. All tumors were excised and did not recur. The tumors typically presented as well-circumscribed nodules with scant or no epidermal connections. (One example, however, had a plate-like configuration amply connected with the basal layers of the epidermis.) The proliferation consisted of multiple, rounded lobules of basaloid cells with some degree of peripheral palisading, immersed in a dense, fibrous stroma. There was an intense infiltrate of small lymphocytes within the lobules, with some spillage into the stroma. No clear adnexal differentiation was noted except for rare isolated cells showing apparent sebaceous differentiation within the tumor lobules. Areas of central keratinization were also present. Numerous cells with ample amphophilic cytoplasm, large vesicular nuclei, and prominent nucleoli were also seen. Immunohistochemistry confirmed the presence of keratin within tumor cells. Common leukocytic antigen highlighted the intense intralobular lymphocytic component. Vimentin not only highlighted the stromal fibroblastic component, but also stained scattered intralobular cells. Epithelial membrane antigen was positive within some of the large intraepithelial cells. S-100 protein was extensively positive within dendritic intralobular and stromal cells. Lymphocytic markers demonstrated a polyclonal B and T population. This unique tumor appears to represent a form of adnexal neoplasm with basaloid features, possibly immature pilosebaceous differentiation.

Cutaneous malignant melanotic neurocristic tumors arising in neurocristic hamartomas. A melanocytic tumor morphologically and biologically distinct from common melanoma.

Cutaneous neurocristic hamartomas (CNH) are pigmented lesions of neural crest origin that involve the skin and superficial soft tissue. They consist of a complex proliferation of nevomelanocytes, schwann cells, and pigmented dendritic and spindled cells. Malignancies can arise within the lesions, but few studies have dealt with this issue. We studied seven cases of CNH in which malignancy supervened. They included four congenital and three acquired lesions that involved the head and neck (five cases) or back (two cases) in patients aged from 11 to 67 (mean, 32) years. Malignant tumors developed 15 to 67 (mean, 32) years after identification of the pigmented lesion in the congenital CNH and after 1 to 6 (mean 3.5) years in the acquired CNH. The malignant tumors had a deep intradermal or subcutaneous origin and lacked a junctional component. Most were circumscribed, multinodular, melanin-containing tumors composed of bland, small, rounded to spindled cells, focally displaying a trabecular or nested growth pattern. Nuclear palisading and perivascular pseudorosettes were present in several tumors. In two examples, the neoplasm consisted predominantly of large pleomorphic epithelioid cells. Tumors contained immunoreactive S-100 protein (all of seven cases), a melanoma-associated antigen (HMB-45)( five of six cases, neuron-specific enolase (five of seven cases) and vimentin (six of six cases). The four patients with congenital lesions tended to have multiple recurrences and died of disease after 2 to 20 (mean, 9) years, three with metastases, one with direct invasion of the posterior fossa. The three patients with acquired lesions are alive after 1 to 5 years two with persistent disease. In contrast to common melanomas, these tumors have a propensity to recur as bulky nodules and to metastasize after many years or decades. Because these tumors exhibit melanocytic differentiation and arise in hamartomatous lesions composed of neural crest derivatives, we have designated them cutaneous malignant melanotic neurocristic tumors.

Sclerosing sweat duct (syringomatous) carcinoma.

This report describes 20 sclerosing adnexal carcinomas of the skin that recapitulate the sweat duct and share certain microscopic features with benign syringoma. Clinically, the neoplasms were slow-growing, indurated nodules or plaques. Sixteen were located on the face, including five on the upper lip. Three were situated in the axilla, and one involved the buttock. Twelve of the tumors (group 1) were composed primarily of cords and nests of whorled squamous cells with clear cell change and variable keratinization. Lumens consistent with ductal differentiation were few and isolated in some of these lesions, but others had more numerous and complex ducts. The remaining eight neoplasms (group 2) contained large numbers of small, uniform ducts, and exhibited little keratinization. Each neoplasm in the series infiltrated subcutaneous tissue or deeper tissues and was accompanied by sclerotic, fibrous stroma. Sixteen of the lesions (80%) exhibited perineural growth. One tumor involved an underlying lymph node, probably by direct extension. Cytologic atypicality was mild or lacking, and mitotic figures were sparse. Seven of 15 tumors (47%) with follow-up recurred, in some instances many years after primary excision. Tumor-free margins in the initial excision specimen appeared to be a favorable prognostic factor. The most aggressive lesion in the series showed increased cytologic atypicality in recurrences.

Site-dependent phenotypic heterogeneity in peripheral T-cell lymphoma.

Peripheral T-cell lymphomas constitute a heterogeneous population of postthymic T-cell malignancies. Characteristically, they present a varied phenotypic expression, which can be helpful in establishing the diagnosis. A case of a peripheral T-cell lymphoma in a 76-year-old man is described. The malignant cells in the skin and bone marrow were of the T4 (helper/inducer) phenotype, yet they did not express pan-T-cell antigens, such as T11, or functional E rosettes. In a biopsy specimen from a lymph node, however, the malignant cells had a helper/inducer phenotype and also expressed the pan-T-cell antigens T11 and Leu-5. Additionally, the malignant cells from the lymph node formed E rosettes. This study demonstrates the phenotypic heterogeneity of malignant T cells, which appears to be site-dependent.

Periocular granuloma annulare, nodular type. Occurrence in late middle age.

We describe the two oldest individuals with nodular granuloma annulare (pseudorheumatoid nodules) in the ophthalmologic literature and propose a unified classification scheme that recognizes pseudorheumatoid nodules to be granuloma annulare, nodular type. All lesions in both cases revealed so-called necrobiotic granulomas, characterized by an acellular central area containing mucin (hyaluronic acid) surrounded by palisading histiocytes (macrophages), diagnostic of granuloma annulare. These features are identical to those reported in the ophthalmologic and older general pathology literature as pseudorheumatoid nodules and the contemporary general and dermatologic pathology literature as granuloma annulare. We believe the diagnosis of nodular granuloma annulare should be employed for necrobiotic lesions displaying distinctive clinicopathologic features to unite the ophthalmologic, general, and dermatologic pathology literature. Granuloma annulare, nodular type, must also be considered in the differential diagnosis of ocular and periocular lesions at any age.

Differentiating neoplasms of hair germ.

Differentiating neoplasms of hair germ are benign epithelial-mesenchymal tumours of skin in which hair follicle development may be partly or completely recapitulated. The epithelial component is equivalent to the hair germ. The mesenchymal component is equivalent to the dermal papilla. Epithelial-mesenchymal interaction results in the morphogenesis of hair follicles. In neoplasms showing stromal induction, there is centrifugal organizations: hair bulbs are found at the periphery of tumour lobules and hairs are projected centrally to lie within small keratinizing cysts. Neoplasms of hair germ without advanced morpho-differentiation are termed ;trichoblastomas', and those neoplasms in which hair follicle development is advanced are called ;trichogenic trichoblastomas'.

Anaerobic bacteria in routine urine culture.

One hundred and fifty-eight anaerobic organisms from 147 patients were isolated from 15,250 consecutive clean mid-stream or catheter urine specimens. The pathogenicity of the anaerobic genera commonly isolated from urine is reviewed and discussed. Failure to establish anaerobic isolates as pathogens and a paucity of reported cases proving anaerobic bacteria as significant causes of urinary tract infection permitted discontinuation of anaerobic culture as part of the routine screening procedure for investigation of urinary tract infections.

Telogen effluvium. New concepts and review.

BACKGROUND: Telogen effluvium is the result of a perturbation of the hair cycle that is manifest by increased loss of normal club hairs. Although diverse causes for telogen effluvium have been proposed, this article suggests several diverse mechanisms for the first time. OBSERVATIONS: Five different functional types of telogen effluvia are proposed based on changes in different phases of the follicular cycle. These are immediate anagen release, delayed anagen release, short anagen syndrome, immediate telogen release, and delayed telogen release. Diverse causes are confirmed and drug-related telogen effluvia are reviewed. CONCLUSIONS: The five diverse mechanisms proposed for telogen effluvia are generally confirmed and supported by clinical findings.

Transverse microscopic anatomy of the human scalp. A basis for a morphometric approach to disorders of the hair follicle.

Transverse sections of cylindrical scalp biopsy specimens can provide excellent samples for histologic, quantitative morphometric analyses of the follicles and hair. This study describes and illustrates the morphologic details of the normal transverse anatomy of follicular structures, including the various phases of the normal hair cycle.

Psammomatous melanotic schwannoma. A new cutaneous marker for Carney's complex.

BACKGROUND: Noncutaneous psammomatous melanotic schwannoma has recently been reported as an unusual component of Carney's complex (myxomas, spotty pigmentation, and endocrinopathy). The most common locations for this lesion include peripheral nerve roots and the gastrointestinal tract. OBSERVATIONS: A cutaneous psammomatous melanotic schwannoma is reported in a patient with known Carney's complex. This neoplasm was pseudoencapsulated, with epithelioid to spindle-shaped cells and no nuclear atypia. Immunostaining was positive for S100 protein and vimentin, as well for HMB-45 antibody. Electron microscopy showed melanosomes in cytoplasmic processes of cells that were ensheathed by layers of reduplicated basal lamina. CONCLUSIONS: Location in the superficial soft tissues is extremely unusual for psammomatous melanotic schwannomas. Recognition of this new cutaneous marker as a part of this complex may aid in identification of individuals at risk for cardiac myxomas. It is also important that this lesion is not mistaken for melanoma, given the strong HMB-45 positivity.

Bowen's and non-Bowen's squamous intraepidermal neoplasia of the skin. Relationship to internal malignancy.

The relationship of Bowen's disease to internal malignancy is controversial. We have studied 72 cases of Bowen's disease and compared them with 58 cases of non-Bowen's squamous intraepidermal neoplasia (SIN). Clinical data were obtained in all cases in an attempt to identify carcinogens and to detect the occurrence of other cutaneous or internal malignancies. Internal malignancy was not found more commonly in patients with Bowen's disease than in those with other forms of SIN. However, 5.7% of all patients win SIN were found to have a concurrent internal malignancy. Other cutaneous malignancies were also more frequent in these groups and may relate to sun exposure. Evidence for arsenic ingestion was not found in most patients. We believe that SIN either as Bowen's or non-Bowen's type may serve as an important marker for the presence of internal malignancy.

Primary granulomatous dermatitis caused by Rhodochrous. Evidence for a pathogenic role in humans.

Bacteria belonging to the Rhodochrous complex are of uncertain taxonomic status. Currently excluded from the genus Mycobacterium, these organisms are more closely allied to Nocardia. Organisms of the Rhodochrous complex have only rarely been implicated as human pathogens. An 81-year-old man had a plaquelike cutaneous granuloma from which Rhodochrous was both cultured and demonstrated in tissue section. A pathogenic role for Rhodochrous causing a primary cutaneous infection is suggested. Specific antimicrobial treatment with doxycycline hydrochloride was successful and there has been no recurrence of the infection after three years.

Familial focal alopecia. A new disorder of hair growth clinically resembling pseudopelade.

A 14-year-old girl was evaluated for patchy hair loss present from early childhood. Her mother was found to have a similar condition. When studied in transverse section, biopsy specimens from both women showed marked anagen-telogen transformation that circumstantially appears to be irreversible. Preservation of telogen epithelium with absence of inflammation and scarring readily separate focal familial alopecia from the pseudopelade state and from localized alopecia areata. To our knowledge, this is the first description of a new familial disorder causing focal alopecia.

Purpura fulminans. A cutaneous manifestation of severe protein C deficiency.

Protein C, when activated, is a vitamin K-dependent serine protease that has anticoagulant and profibrinolytic activities. An increased risk of thrombotic disease is associated with deficiency of this enzyme. A neonate developing purpura fulminans with internal thrombotic complications and congenital absence of protein C is described. Family studies showed partial protein C deficiency in the subject's symptom-free parents and two of three siblings. Clinically and histopathologically similar lesions are also seen in two acquired conditions in which there is a thrombotic tendency: coumarin necrosis and purpura fulminans of childhood, both of which are probably the result of transient protein C deficiency. We conclude that purpura fulminans can represent a cutaneous marker of acquired or congenital protein C deficiency.

Fibroblastic rheumatism.

BACKGROUND: Fibroblastic rheumatism was first described in the French literature in 1980. Since that time, 11 other patients with this disorder have been identified in the literature, mostly from France. This is a unique syndrome characterized by the sudden onset of symmetric polyarthritis and cutaneous nodules ranging from 5 to 20 mm in diameter, with predilection for the upper and lower extremities. While the cutaneous findings resolve spontaneously after several months, permanent joint sequelae are common. OBSERVATIONS: We present the first two patients with fibroblastic rheumatism reported in the United States. The clinical features and histologic findings were identical to those of patients described in the European literature. CONCLUSIONS: Fibroblastic rheumatism is a relatively rare syndrome characterized by the association of multiple cutaneous nodules with polyarthritis. The clustering of cases in France may, in part, be attributable to increased recognition by clinicians owing to prevalence of reports in the European literature. Perhaps, as clinicians in the United States become familiar with this disorder, further cases will be diagnosed, and the pathogenesis of the disorder will be elucidated.

Epithelioid sarcoma. Enzymatic histochemical and electron microscopic evidence of histiocytic differentiation.

A 63-year-old man had epithelioid sarcoma. Light microscopy showed the tumor to resemble granuloma annulare. Enzymatic histocytochemical and ultrastructural studies demonstrated the tumor's histiocytic features. Literature review of epithelioid sarcoma and granuloma annulare showed them to have a similar anatomic distribution.

Nylon brush macular amyloidosis.

Long-term use of a nylon brush for back scratching by a 53-year-old white woman was associated with the development of typical macular amyloidosis. EKH4 monoclonal antikeratin antibody, which recognizes 50-kd neutral and acidic keratin species, labeled this amyloid. Confirmation of amyloid substance in the lesion included positive staining with Dylon and thioflavin T; immunohistochemical reactions with monoclonal and polyclonal antibodies against elastic fiber microfibrils (NKH1 and anti-P component), immunoglobulins (IgG, IgM, and IgA), and complement (C3); and electron microscopic identification of 6- to 10-nm straight filaments. Type IV collagen staining demonstrated a breakage and/or thickening of the dermoepidermal basement membrane above the amyloid deposition in the papillary dermis. Electron microscopic findings confirmed this phenomenon.

Cutaneous myxomas. A major component of the complex of myxomas, spotty pigmentation, and endocrine overactivity.

Cutaneous myxoma(s) occurred in 22 (54%) of 41 patients with the complex of myxomas, spotty pigmentation, and endocrine overactivity. Of the 16 patients who had cardiac myxoma(s), the cutaneous tumor(s) was (were) detected in 13 (81%) of them prior to diagnosis of the cardiac neoplasm. Thus, the cutaneous tumor may herald a potentially fatal cardiac neoplasm (and other important conditions as well). Clinical features of the lesion were as follows: early appearance (mean age, 18 years); multicentricity (71% of patients); small size (usually less than 1 cm in diameter); widespread distribution but with predilection for certain sites (eyelids, ears, nipples); and tendency for recurrence. Pathologic features included the following: location in dermis, subcutis, or both; sharp circumscription (sometimes encapsulation); hypocellularity; abundant myxoid stroma; prominent capillaries; lobulation (larger lesions); and occasional presence of an epithelial component.

Primary adenoid cystic carcinoma of skin.

Two primary adenoid cystic carcinomas of skin were studied histologically and histochemically. Histologically, they closely resemble adenoid cystic carcinoma found in other tissues but in the skin must be distinguished from aggressive basal cell carcinomas. The natural history of these tumors and of those collected from the literature suggest a long indolent and progressive course. Local excision with meticulous histologic control of the surgical margins appears to be an appropriate therapeutic strategy. Thus far lymph node metastases have not been observed.