Advanced basal cell cancer: concise review of molecular characteristics and novel targeted and immune therapeutics.

Metastatic basal cell carcinoma is an ultra-rare manifestation of a common disease, appearing in 0.0028%-0.5% of basal cell carcinomas. Initial therapeutic efforts focused on cytotoxic chemotherapy administration. However, it is now known that the Hedgehog signaling pathway is crucial for basal cell proliferation and Hedgehog pathway mutations may lead to tumorigenesis; thus, small-molecule inhibitors of alterations in the components of this pathway, including smoothened (SMO) and GLI, have been the focus of recent therapeutic developments. Indeed, the European Medicines Agency and the Food and Drug Administration have approved the SMO inhibitors, vismodegib and sonidegib, with additional GLI inhibitors currently in clinical trials. Molecular profiling of these tumors has revealed other potential targets for therapy, including high tumor mutational burden and PD-L1 amplification, which predict response to immune checkpoint blockade (PD-1 and PD-L1 inhibitors). An illustrative patient with a giant, advanced, unresectable basal cell carcinoma who obtained an ongoing complete remission after treatment with a combination of an immune checkpoint inhibitor (due to the tumor's high mutational burden) and the Hedgehog inhibitor vismodegib is described. A fuller understanding of the genomic portfolio of these patients can assist in developing novel, rational therapeutic approaches that should continue to improve responses and outcomes.

From members to teams to committee-a robust approach to gestural and multimodal recognition.

When building a complex pattern recognizer with high-dimensional input features, a number of selection uncertainties arise. Traditional approaches to resolving these uncertainties typically rely either on the researcher's intuition or performance evaluation on validation data, both of which result in poor generalization and robustness on test data. This paper describes a novel recognition technique called members to teams to committee (MTC), which is designed to reduce modeling uncertainty. In particular, the MTC posterior estimator is based on a coordinated set of divide-and-conquer estimators that derive from a three-tiered architectural structure corresponding to individual members, teams, and the overall committee. Basically, the MTC recognition decision is determined by the whole empirical posterior distribution, rather than a single estimate. This paper describes the application of the MTC technique to handwritten gesture recognition and multimodal system integration and presents a comprehensive analysis of the characteristics and advantages of the MTC approach.

Metastatic tumors to the nail unit: subungual metastases.

BACKGROUND: Cutaneous metastases are variable in location and morphology. Metastatic tumor can present as a subungual lesion in either an oncology patient or a previously cancer-free individual. However, the diagnosis of a subungual metastasis is often not initially considered since the symptoms and appearance of the subungual tumor frequently mimic those of other conditions. OBJECTIVE: To describe the clinical characteristics, radiographic changes, and pathologic findings of the subungual metastases in two women with metastatic carcinoma and to discuss the features of metastatic tumor lesions to the subungual area and distal digits previously reported in oncology patients. METHODS: The clinical presentation, radiologic studies, and pathologic examination of metastatic subungual tumor lesions were described in two oncology patients: a woman with breast cancer and a woman with renal cell carcinoma. The published reports of cancer patients with subungual metastases were reviewed and the following variables were evaluated: the primary origin of the cancer, the histology of the primary tumor, the temporal relationship between the onset of symptoms or the appearance of subungual metastasis and the diagnosis of the visceral malignancy, the symptoms and the morphology of the subungual metastases, the clinical differential diagnosis of subungual metastases, the relationship between the site of origin of the primary tumor and the incidence of metastases either to the fingers and the thumbs or to the toes, the distribution of subungual metastases, the incidence of radiologically confirmable bony involvement of the distal phalanx by metastatic tumor in the digit containing the subungual metastasis, and the prognosis of patients in whom the diagnosis of a subungual metastasis has been confirmed. RESULTS: Subungual metastases most frequently occur in patients with primary tumors of the lung (41%), genitourinary tract organs (17%, of which the kidney represents 11%), and breast (9%). The histology of the primary tumors that was most common included renal cell carcinoma and squamous cell carcinoma. The appearance of the subungual tumor was the first sign of a previously unsuspected primary malignancy in 44% of the patients with subungual metastases. Subungual metastases were frequently painful and most often presented as either an erythematous enlargement or swelling of the distal digit or a red to violacious nodule that distorted either the nail plate or the soft tissue of the distal digit, or both. The lesion was often initially mistaken as an acute infection. The lesion involved one or more digits of the hands in 92% of patients with subungual metastases; symmetrical subungual metastases and metastatic tumor restricted only to the great toes were less commonly observed. In patients with subungual metastases that involved the digits of their hands, the most frequent sites of primary tumor origin were the lung (35%) and the genitourinary tract organs (25%). Radiologic evidence of bony involvement of the respective distal digit was either initially present or subsequently developed in 92% of patients with subungual metastases. Patients with subungual metastases have a poor prognosis; their survival following the diagnosis of the subungual tumor is usually only a few months. CONCLUSION: The clinical differential diagnosis of a new periungual or subungual lesion (with or without an associated nail plate dystrophy) should include tumor metastasis to the nail unit not only in oncology patients, but also in previously cancer-free individuals.

Sebaceous hyperplasia: a clue to the diagnosis of dermatofibroma.

We describe a man with an indurated lesion on his upper back that showed a dermatofibroma with overlying sebaceous hyperplasia. Characteristic dermal features of a dermatofibroma may be sparse or absent in a lesional specimen that has been submitted subsequent to a superficial shave biopsy. Hyperplasia of sebaceous glands in a nonfacial lesion is a histologic feature that should prompt the search for a dermatofibroma in the underlying dermis.

Subacute cutaneous lupus erythematosus: report of a patient who subsequently developed a meningioma and whose skin lesions were treated with isotretinoin.

Cancer has been reported in patients with systemic lupus erythematosus (SLE). A possible association of the development of hematologic malignancies in patients with SLE has been suggested. In some patients, subacute cutaneous lupus erythematosus, a distinct subset of lupus erythematosus, has appeared, resolved, or both as a solid tumor-related paraneoplastic syndrome. A woman in whom a meningioma was diagnosed 44 years following the onset of subacute cutaneous lupus erythematosus is described; her skin lesions improved after starting isotretinoin therapy. The relationship between lupus erythematosus and neoplasia is summarized and the management of subacute cutaneous lupus erythematosus with retinoids is reviewed.

Recurrent sclerotic fibroma of the skin.

The pathologic findings of a sclerotic fibroma of the skin may resemble those of other benign cutaneous lesions. In this report, the sequential pathologic changes of a recurrent sclerotic fibroma of the skin during a period of 7 years are documented. As the lesion became older, there was not only a decrease in cellularity, but also a progressive organization of the collagen bundles toward a "plywood-like" appearance.

Cutaneous lesions of metastatic visceral malignancy mimicking pyogenic granuloma.

Cutaneous metastases may be the first sign of a previously undiagnosed visceral malignancy or the initial presentation of a recurrent neoplasm. Rarely, skin metastases can resemble a pyogenic granuloma. Three oncology patients who developed new pyogenic granuloma-like cutaneous lesions are described. Histopathologic examination showed metastatic visceral malignancy in the skin. The characteristics of the previously reported cancer patients with metastatic tumor to the skin that mimicked a pyogenic granuloma are reviewed. A biopsy of a skin lesion that clinically appears to represent a pyogenic granuloma should be performed for microscopic examination in patients with a previous visceral malignancy or in cancer-free individuals whose lesions do not resolve after conservative treatment.

Ectopic hidradenoma papilliferum: a case report and review of the literature.

Hidradenoma papilliferum is a benign, cystic, papillary tumor that occurs almost exclusively in women on the skin of the anogenital region. Nonanogenital (ectopic) hidradenoma papilliferum are rare. We describe a 72-year-old white man with an enlarging nodule in the region of the right triceps muscle; microscopic examination showed a hidradenoma papilliferum. The median age of patients with ectopic hidradenoma papilliferum is between 1 to 2 decades older than the average age range of lesion onset in patients with anogenital hidradenoma papilliferum. In contrast to anogenital hidradenoma papilliferum, nearly one half of the patients with ectopic hidradenoma papilliferum are men. Ectopic hidradenoma papilliferum occurs most frequently (60%) in the head and neck region. Eighty-five percent of cases are 1.5 cm in the greatest diameter or smaller. The race, clinical features, pathologic features, treatment, and prognosis for hidradenoma papilliferum occurring in anogenital and ectopic locations are similar.

Ichthyosiform sarcoidosis.

Ichthyosiform sarcoidosis is a rare specific cutaneous manifestation of sarcoidosis; it clinically and microscopically appears as acquired ichthyosis. We report a 68-year-old black man with a 10-year history of chronic obstructive pulmonary disease who presented with a 2-month history of acquired ichthyosis. His skin biopsy specimen showed both noncaseating granulomas in the dermis, consistent with sarcoidosis, and ichthyosis vulgaris. Ichthyosiform sarcoidosis is an uncommon presentation of cutaneous sarcoidosis that has been previously described in 19 nonwhite patients whose lesions were located on the legs. The skin lesions appeared either concurrently with or preceded the diagnosis of systemic sarcoidosis in 76% of patients; 95% of the patients eventually developed systemic involvement of their sarcoidosis. The onset of acquired ichthyosis should prompt evaluation for an associated malignancy, connective tissue disease, endocrine abnormality, nutritional deficiency, drug reaction, or sarcoidosis. A skin biopsy specimen consistent with acquired ichthyosis may point to the presence of cutaneous sarcoidosis.

Annular elastolytic giant cell granuloma.

A 49-year-old woman had large annular lesions with raised erythematous borders and atrophic, hypopigmented central regions on her neck, trunk, and proximal upper extremities. Examination of a biopsy specimen demonstrated a granulomatous infiltrate in the upper dermis that surrounded areas lacking elastic fibers; elastic fibers were present within the multinucleated giant cells. The clinical presentation and pathologic findings were consistent with a diagnosis of annular elastolytic giant cell granuloma (AEGCG). The clinical description and pathologic differential diagnosis of AEGCG are reviewed.

Nevus with fat: clinical characteristics of 100 nevi containing mature adipose cells.

BACKGROUND: The presence of mature adipose cells among the dermal melanocytes of nevi (nevi with fat) has previously been reported. However, its clinical features are not well characterized. OBJECTIVE: Our goal was to develop a better clinical understanding and insight into the histogenesis of nevi with fat by characterizing the patients' age, sex, height, weight, and location of lesion. METHODS: This was a prospective study of 100 nevi with fat from 89 patients over an 18-month period. RESULTS: Nevi with fat occur 4 times more commonly in women than men. They were diagnosed most often in patients between the ages of 40 to 49 years. The most frequent location is the head and neck. Most nevi with fat are intradermal. CONCLUSION: The appearance of fat within nevi is probably a multifactorial process. Age, weight, and sun exposure may be factors associated with the occurrence of nevi with fat.

Central focal interface opacity after laser in situ keratomileusis.

BACKGROUND: The acute onset of a focal central interface opacity with visual loss following LASIK has not been described in the peer reviewed literature. Non-peer reviewed reports of various inflammatory lesions have been recorded. METHODS: We describe three cases in which an acute focal stromal interface opacification was identified within 1 week of laser in situ keratomileusis (LASIK). Each case was performed by a different surgeon on a different day, but using the same method, materials, and the Summit Apex Plus excimer laser. Immediately after surgery, all eyes were normal with good unaided vision. The appearance of the central stromal opacity was associated with acute visual deterioration. Preoperative and postoperative cycloplegic refractions, videokeratography, and postoperative slit-lamp biomicroscopy were performed. Each case was treated with intensive topical corticosteroids. RESULTS: Each case demonstrated a central circular opacity in the interface between corneal flap and stromal bed, with associated variable stromal thinning. Resolution of the pathological process followed 2 to 4 weeks of treatment with topical corticosteroids and subsequent improvement in slit-lamp biomicroscopy, corneal topography, and vision. Etiology was uncertain. CONCLUSION: Central interface opacification is a rare but visually important inflammatory complication of LASIK.

Accelerated cutaneous nodulosis during methotrexate therapy in a patient with rheumatoid arthritis.

Rheumatoid nodulosis is characterized by multiple small subcutaneous granulomatous nodules typically located on the elbows in approximately 20% of patients with rheumatoid arthritis. Accelerated rheumatoid nodulosis, especially involving the hands and feet, has recently been reported in patients receiving methotrexate therapy for rheumatoid arthritis. We describe a woman with seropositive, erosive rheumatoid arthritis who, on two occasions, developed nonperiarticular subcutaneous nodules and new heart murmurs during methotrexate therapy, while her arthritis remained under good control. The nodules resolved after methotrexate was discontinued and recurred after methotrexate was reintroduced. They again resolved after methotrexate was stopped and colchicine was added. Her DNA oligotyping was positive for HLA-DRB1*0401, a genetic risk factor associated with accelerated rheumatoid nodulosis. Cutaneous biopsy specimens revealed palisading granulomas and giant cells consistent with rheumatoid nodulosis.

Trichilemmal horn: case presentation and literature review.

A trichilemmal horn is a histologically unique, uncommonly reported lesion, characterized by a plate-like nodule that extends from the epithelium into the dermis and has a prominent basement membrane. At the periphery of the nodule, there is palisading of basal cells. Trichilemmal keratinization is present in the overlying horn and is composed of orthokeratosis with focal parakeratosis. We describe a 22-year-old white women with a trichilemmal horn on her left elbow and review the literature. With the addition of our patient, trichilemmal horns have been described in 28 patients. They have been observed more often in women (15) than in men (11). The patients ranged in age from 16 to 78 years; more than 60% were 50 years of age or older. Trichilemmal horns were most common on the extremities (12 cases) and the head (11 cases). The diagnosis of a trichilemmal horn should be considered when a cutaneous horn shows trichilemmal keratinization in the absence of dermal inflammation.

Syringomatous changes of eccrine sweat ducts associated with prurigo nodularis.

Alteration of the eccrine sweat ducts has been observed in association with an expanding list of conditions. To our knowledge, this phenomenon has not been described in association with prurigo nodularis. We report on a 68-year-old man with a fibrotic nodule on his chin that had been present for 8 months. Microscopic examination showed marked hyperkeratosis overlying the epithelium. There was also hypergranulosis, marked acanthosis, and irregular elongation of the rete ridges. These findings were consistent with prurigo nodularis. In addition, within the reticular dermis, there was marked fibrosis and a proliferation of eccrine sweat ducts. The ducts were enlarged and varied from cystic to rarely solid structures. Rare ducts formed a tadpole-shaped tail, reminiscent of syringoma. The duct lining demonstrated a multilayered epithelium that was three to eight cells thick, yielding a solid component to some of the cysts. Although some of these features were similar to those of a syringoma, the typical small gland proliferation and bilayered lining was not evident. This case (a) demonstrates the association of syringomatous changes of eccrine sweat ducts with yet another condition, prurigo nodularis, and (b) emphasizes the importance of differentiating this benign reactive process from the malignant neoplasms microcystic adnexal carcinoma and squamous cell carcinoma.

Iatrogenic necrolytic migratory erythema: a case report and review of nonglucagonoma-associated necrolytic migratory erythema.

Necrolytic migratory erythema is characterized by waves of irregular erythema in which a central bulla develops, and subsequently erodes and becomes crusted. It usually occurs in patients with an alpha-islet cell tumor of the pancreas. However, necrolytic migratory erythema has also been observed in patients without an associated glucagonoma. We describe a woman with iatrogenic necrolytic migratory erythema. She received intravenous glucagon for hypoglycemia associated with an insulin-like growth factor II-secreting hemangiopericytoma. After chemotherapy, she developed necrolytic migratory erythema. The characteristics of the previously reported patients with nonglucagonoma-associated necrolytic migratory erythema are reviewed. In patients with nonglucagonoma-associated necrolytic migratory erythema, the dermatosis-related conditions most commonly observed were celiac disease or malabsorption, cirrhosis, malignancy, and pancreatitis; less common conditions included hepatitis, inflammatory bowel disease, heroin abuse, and odontogenic abscess. Although the pathogenesis of necrolytic migratory erythema remains unknown, hyperglucagonemia appears to have had a causative role in the development of this dermatosis in our patient. Patients who develop necrolytic migratory erythema should be evaluated for the presence of a glucagonoma; if a glucagonoma is ruled out, evaluation for other conditions known to occur with necrolytic migratory erythema, such as liver disease, malabsorptive disorders, and nonislet-cell tumors is warranted.