A Subungual Nevoid Melanoma of the Right Hallux from a 65-Year-Old Man: A Case Report.

Nevoid melanoma (NeM) is a rare variant of malignant melanoma characterized by slight cellular atypia, polymorphism, and incomplete maturation. It most frequently occurs on the trunk and arms but rarely on the foot. Here, we report a subungual NeM of the right hallux. A 65-year-old man presented with severe pain of 6 months' duration to his right great toe following self-treatment for an ingrown nail. He was evaluated and treated with debridement of the toenail at an urgent medical center 3 months prior. However, this had not relieved his pain. The patient also noticed discoloration of his distal great toe over the past 3 months. Removal of part of the ingrown nail revealed a pigmented mass extending distally from the matrix. Surgical excision of the mass was performed because of the concern for malignancy. The diagnosis of NeM was based on histologic analysis along with enhanced diagnostic modalities. The patient was further treated with surgical amputation of the great toe and anti-programmed cell death-1 therapy. The patient had no relapse at 1-year follow-up. Nevoid melanoma is a rare variant of malignant melanoma on the toes, which needs to be differentiated from a nevus with atypia, with a variety of modalities including cellular and molecular profiling. The optimal treatment is amputation.

Clinicopathologic Characterization of Kaposi Sarcoma on the Foot and Ankle: Analysis of 11 Patients Seen in Our Clinics.

BACKGROUND: Kaposi sarcoma (KS) has multiple clinical variants, and most frequently presents on the lower extremities. Anti-human immunodeficiency virus (HIV) therapy has significantly reduced the incidence of KS. However, KS is still prevalent in both HIV-infected and HIV-uninfected patients. This case series analysis aims to reveal the clinical presentations, differential diagnosis, and treatment options of KS on the foot and ankle. METHODS: Eleven cases of KS involving the foot and ankle were retrieved from our patient database, and their clinicopathologic features were analyzed. RESULTS: All patients were men, aged 29 to 85 years. Two types of KS were found: classic and acquired immunodeficiency syndrome-associated epidemic. The average ages of classic and epidemic KS were 65.7 and 41.8 years, respectively. Clinically, three patients manifested multiple erythematous or deep violaceous, or blue-violaceous macules on either the dorsal or plantar surfaces of both feet. Eight patients showed exophytic, pyogenic granuloma-like nodules on the plantar surface, heels, and toes. Histologically, all KSs had uniform intervening fascicles of elongated spindle cells with slit-like vascular spaces filled with red blood cells and immunoreactivity with human herpesvirus-8. The patients were treated according to HIV infection status. Human immunodeficiency virus-infected patients were treated with anti-HIV therapy after primary surgical excision or biopsy. Human immunodeficiency virus-negative patients were treated with either surgical excision, Mohs surgery, or a combination of surgical excision and local radiotherapy according to individual patient clinical presentation. CONCLUSIONS: Kaposi sarcoma is still prevalent in both HIV-infected and HIV-uninfected patients with a variety of clinical presentations. Biopsy, with histologic evaluation, in combination with immunohistochemistry is essential for the differential diagnosis. The patient should be treated according their clinical manifestation, staging, comorbidity, and immune function.

Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg Type on the Dorsal Foot in a Senior Woman: A Case Report.

Primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT) is a rare variant of the cutaneous B-cell lymphomas, with rapid growth and poor prognosis. Here, we report a case of PCDLBCL-LT on the foot in a senior woman. An 81-year-old woman presented with a rapidly growing mass on her left foot, and discoloration in both lower legs over the past 2 months was analyzed. Physical examination revealed hyperpigmented macules and papules on both lower extremities and a 3.0 × 2.0 × 0.5-cm, gray-dark nodule on the dorsal surface of the left foot. Histologic observation of the punch biopsy specimen revealed a sheet of atypical large centroblast/immunoblast-like lymphocytes; diffusely and evenly distributed in the dermis; with the immunophenotypes of CD45-positive, CD20-positive, Melan A-negative, Sox10-negative, S-100-negative, and CK20-negative; and a very high Ki-67 proliferative index (>90%). Further punch biopsy specimens of papules in the patient's lower extremities and bone marrow did not reveal atypical lymphoid tissues. Positron emission tomography/computed tomography did not show any metastatic lesions in distant organs and lymph nodes. The lesion was diagnosed as PCDLBCL-LT stage T1N0M0. The patient was treated with four cycles of combined therapy of rituximab and cyclophosphamide, hydroxydaunorubicin, vincristine (Oncovin), and prednisolone and the tumor was further treated with local radiotherapy. The tumor size was significantly shrunken. Primary cutaneous diffuse large B-cell lymphoma, leg type is a rare entity on the foot, characterized by a confluent sheet of diffuse large centroblast- and or immunoblast-like B cells with B-cell immunophenotyping. The combined therapy of rituximab and cyclophosphamide, hydroxydaunorubicin, vincristine (Oncovin), and prednisolone is the first-line treatment regimen, with increased survival.

Mycosis Fungoides Palmaris et Plantaris on the Plantar Aspect of the Foot: A Case Report.

BACKGROUND Mycosis fungoides palmaris et plantaris (MFPP) is a rare variant of the cutaneous T cell lymphoma mycosis fungoides (MF). Here we report the case of a middle-aged man with MF on the sole of his left foot. CASE REPORT A 54-year-old man had a diffuse, hard lesion in the middle of the arch on the sole of his left foot for 3 years. Physical examination revealed a 3-cm scaly, keratotic patch with slight erythema on the left plantar central arch. Histopathological evaluation of a punch biopsy specimen revealed infiltration of atypical lymphocytes in the upper dermis. Immunostaining of the atypical lymphocytes showed strong expression of CD3, CD4, and CD5; reduced expression of CD7 and CD8; and no expression of CD20. Periodic acid-Schiff staining was negative for fungi. The patient's lesion was diagnosed as MFPP and he was treated with topical psoralen plus ultraviolet A (PUVA) photochemotherapy. At 5-year follow-up, his condition was in complete remission. CONCLUSIONS MFPP is a rare clinical variant of MF restricted to the palmoplantar area, and is histologically characterized by upper dermal infiltration of atypical lymphocytes with preserved CD3, CD4, and CD5 expression but decreased CD7 and CD8 expression. PUVA photochemotherapy is a treatment option associated with excellent prognosis.

PAS stain based histological classification and severity grading of toenail onychomycosis.

Onychomycosis is a common world-wide health issue. Accurate detection is essential for treatment. Multiple studies have shown that PAS-stain based histological visualization of fungal elements is superior to either direct microscopy with 20% potassium hydroxide, or fungal culture. However, PAS stain based histological classification and severity grading of onychomycosis are lacking in the literature. Here we reported a fungal detection rate of 47.87% based on an analysis of 13,805 toenails processed for H&E and PAS stains over a three year period. Based on the analysis of fungal density, distribution and infiltrating depth level in 858 PAS-positive toenails, we created a novel PAS stain based histological classification system to classify onychomycosis as occult onychomycosis (OO), focal or diffuse subungual onychomycosis (FSO or DSO), focal or diffuse plate onychomycosis (FPO or DPO), focal or diffuse subungual and plate onychomycosis (FSPO or DSPO) and superficial onychomycosis (SO). The severities of OO, FSO and FPO were graded as mild, DSO and DPO as moderate, FSPO and DSPO as severe infections, which revealed that more than 75% PAS positive toenails were severe infections. Evaluation of 97 paired toenails biopsied pre- and post-treatment from 47 patients demonstrated that the severity of infection was significantly reduced from severe to mild and moderate levels. These data indicate that the current histological classification evaluates not only the severity of the fungal infection but also the response to treatment. We further propose a guideline for treatment of onychomycosis based on the histological classification and severity.

Soft-Tissue Chondroma in the Right Hallux: A Case Report.

Soft-tissue chondroma is a rare, benign tumor. It is predominantly found in the hands and feet, but rarely in the toes. In this article, we report a digital soft-tissue chondroma that presented as a painful nodule of 5 years' duration in a 67-year-old man. Physical examination revealed a round, solid, movable nodule measuring 7 mm in diameter. Radiographs showed faint linear calcifications in the nodule under the right hallux proximal phalanx neck. The mass was completely excised, and pathologic observation revealed a mass composed of mature chondrocytes in a cartilaginous matrix, consistent with a chondroma. Even though this is a benign tumor, it needs to be differentiated from other tumors, including schwannoma, leiomyoma, chondrosarcoma, and others. Surgical excision is the preferred treatment.

Acral Lentiginous Melanoma of Foot and Ankle: A Clinicopathological Study of 7 Cases.

BACKGROUND/AIM: Acral lentiginous melanoma (ALM) is a rare entity on the foot. This study aimed to reveal its clinical presentations, histopathology and treatment options. MATERIALS AND METHODS: Seven cases of ALM involving foot were treated in our Institute in a 3-year period. RESULTS: The patients' age ranged from 38 to 84 years, with a mean of 65. The ratios of males to females and white to non-white were 4:3 and 5:2, respectively. Clinically, ALM presented as asymmetric, irregular shaped, black-brown, variegatedly discolored, papular, verrucoid, ulcerated or nodular lesions with or without pain. All ALMs were treated with either wide local excision (WLE) or toe amputation. Histologically, ALM was characterized by multiple single and nested atypical melanocytes growing along the dermal-epidermal junction, and extending into dermal layer in nodular growth pattern. CONCLUSION: ALM is a rare, asymmetric, irregularly bordered, variegatedly pigmented lesion. WLE or toe amputation is the standard treatment option.

Schwannoma of Foot and Ankle: Seven Case Reports and Literature Review.

BACKGROUND: Schwannoma is most often grown on the trunk, upper and lower extremities, and head and neck, but rarely on the foot. This study aimed to reveal clinical presentations, histopathology and treatment options for schwannoma of the foot. MATERIALS AND METHODS: Seven schwannomas out of 174 soft-tissue tumors on the foot and ankle were retrieved from our Institute in a 3-year period, and 42 schwannomas on the foot and ankle in the literature in a 30-year period were reviewed. RESULTS: The incidence of schwannoma of foot was found to be 4.0%. The patient age ranged from 8 to 84 years, with a mean of 47.4 years. More than 80% of tumors were located on the ankle, heel and plantar aspect. Overall, 77.6% of patients complained about a painful mass. Magnetic resonance imaging revealed a well-circumscribed, round or ovoid mass with iso-intensity signal compared with surrounding neuromuscular tissues on T1-weighted images and hyper-intensity signal on T2. Forty-eight out of 49 patients were treated with surgical excision or enucleation without recurrence in follow-up from 2 months to 4 years. Histologically, schwannoma was composed of hypercellular Antoni A zone with palisaded spindle cells with strong immunostaining for S-100 and hypocellular Antoni B zone with vascularization in myxoid stroma. CONCLUSION: Schwannoma of the foot and ankle is a rare, painful, indurated tumor. Magnetic resonance imaging reveals the location, size, texture and relationships with surrounding neuromuscular structures. Surgical excision is the primary treatment option with excellent outcome.

Dermatofibrosarcoma Protuberans on Adult Toes: A Case Report and Review of the Literature.

BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) is an uncommon, low-grade, dermal soft-tissue neoplasm with high recurrence, but low metastatic potential. It mainly occurs on the trunk, proximal extremity, head and neck, but rarely on the toes. Herein we report a case of DFSP on the right hallux. CASE REPORT: A 39-year-old male presented with a mass in the right great toe of 3.5 years. After surgical excision, histopathological evaluation of the mass showed elongated monomorphic spindle cells arranged in a storiform pattern. The tumor cells infiltrated into adjacent adipose tissue in a honeycomb formation. Immunostaining for CD34 showed diffuse and strong cytoplasmic expression in neoplastic cells, whereas that for alpha smooth muscle actin, factor XIIIa, S-100 and melan-A were negative. The tumor was diagnosed as DFSP. We further reviewed the literature of DFSP on the toes with the aim to reveal, for the first time as far as we are aware, its clinical presentations, histopathology, differential diagnosis and treatment options. CONCLUSION: DFSP on adult toes is a rare neoplasm characterized by monomorphic spindle cells arranged in storiform pattern, and can be treated with partial or total toe amputation, or wide local excision after primary excision, with excellent prognosis.

Digitized microscopy in the diagnosis of bladder cancer: analysis of >3000 cases during a 7-month period.

BACKGROUND: Fluorescent in situ hybridization (FISH) analysis of urine samples has proven to be a valuable adjunctive test to urine cytology for both diagnosis and monitoring recurrence of urothelial carcinoma. Automated FISH analysis has the potential to improve laboratory efficiency and to reduce interobserver and intraobserver variability, resulting in more accurate, reproducible, assay performance. METHODS: A total of 3200 slides containing urine specimens, hybridized with the UroVysion Bladder Cancer Kit (Abbott Molecular, Des Plaines, Illinois), a 4-probe set for chromosomes 3, 7, 17, and 9p21, was evaluated at Acupath Laboratories. The slides were analyzed over a 7-month period, using the Ikoniscope - oncoFISH bladder Test System (Ikonisys, New Haven, Connecticut). RESULTS: Analysis included the incorporation of a "flagging" system developed by Acupath Laboratories to identify cases, based on specific criteria, likely to benefit from further manual review. By using US Food and Drug Administration (FDA)-cleared scoring criteria, 96.3% of the slides could be reported directly from the automated scan, requiring no manual review of the slide. For the remaining 3.7% of the samples (all of which were very hypocellular), a manual review of each slide subsequently allowed diagnoses to be successfully reported. The average scan time was 31.7 minutes, and the average slide scan review time was 8.3 minutes. CONCLUSIONS: This study demonstrated the value of an automated approach to the analysis of FISH slides, affording the benefit of high-throughput while providing the user with the necessary images and tools to quickly and accurately report a case.

DC-LAMP stains pulmonary adenocarcinoma with bronchiolar Clara cell differentiation.

DC-LAMP is a molecule expressed in mature dendritic cells, but its mRNA is also found in the lung. This study compares the immunostaining spectrum of PE-10, an antisurfactant protein monoclonal antibody; thyroid transcription factor-1 (TTF-1); and DC-LAMP in normal and neoplastic lung in an attempt to characterize the cell type(s) that express DC-LAMP. Electron microscopy was used to define cell types. DC-LAMP marks pulmonary adenocarcinomas that show Clara cell characteristics by electron microscopy. In contrast, PE-10 labels tumors that have Clara cell and type II pneumocyte differentiation. DC-LAMP staining was lost in solid type adenocarcinomas but persisted in well-differentiated areas. CC-10, an antibody that marks Clara cells, was also positive in tumors that labeled for DC-LAMP. There was no prognostic difference in tumors that reacted with DC-LAMP. DC-LAMP and CC-10 reactivity was also observed in endometrial adenocarcinomas but not in other tumor types.

Histologic features are important prognostic indicators in early stages lung adenocarcinomas.

This study attempts to evaluate the clinicopathologic features of mixed subtype adenocarcinomas and the prognostic implications of histopathology classifications. Surgical specimens from 141 patients with clinical stage I or II lung adenocarcinoma during the period 1992-2004 were included. These cases were classified into four groups defined by the extent of the bronchioloalveolar carcinoma component: group I: pure bronchioloalveolar carcinoma; group II: mixed subtype with predominant bronchioloalveolar carcinoma component and < or = 5 mm invasive component; group III: mixed subtype with bronchioloalveolar carcinoma component and > 5 mm invasive component; group IV: invasive carcinoma with no bronchioloalveolar carcinoma component. Descriptive statistics were used to examine the groups with respect to age, tumor size, lymph node metastasis, and Ki-67 and p53 expression levels. Death rate for the groups was obtained by patient's charts and from the National Death Index database. The population was similar in age, tumor size and lymph node metastasis. Immunohistochemical results showed that the mean Ki-67 labeling and the amount of p53 overexpression had the same trend of increasing mean values or positive results from groups I to IV. The reported proportion of deaths ranged from 0% for groups I and II, 20% in patients with predominant invasive component with bronchioloalveolar carcinoma (group III), and 18% in patients with invasive carcinomas and no bronchioloalveolar carcinoma component (group IV). The difference between the proportion of patients with reported deaths in the time period of this study in the combined greater than 5 mm+pure invasive groups (groups III, IV), and the < 5 mm + noninvasive groups (groups I, II) is statistically significant. These results suggest that histological features may be useful in defining categories of lung adenocarcinomas with differing survival and prognostic features. These results are helpful in defining a subcategory of 'minimally invasive adenocarcinoma', which has features similar to bronchioloalveolar carcinoma.

Fine-needle aspiration cytology of epithelioid angiosarcoma: a diagnostic dilemma.

A 28-year-old woman with a 2-yr history of unilateral chronic leg swelling, initially thought to be secondary to deep vein thrombosis, later thought to be due to congenital venous malformation, eventually developed a pelvic mass, which was biopsied by fine-needle aspiration. On the basis of cytologic features on smears, high-grade sarcoma was reported. The patient underwent surgery to resect the pelvic mass, which showed anastomosing vascular channels arising from external iliac vein in histology. However, the tumor cells unexpectedly showed strong and diffuse immunohistochemical expression of cytokeratin and epithelial membrane antigen. The case was sent for expert consultation, and the expert's opinion was epithelioid angiosarcoma. The expert's diagnosis was confirmed 2 yr later by local recurrence. The clinical presentation, cytology, histology, and immunohistochemistry of the current case and 15 other cases of epithelioid angiosarcoma found in the cytology literature are summarized. This case illustrates that morphology with clinicopathologic correlation tends to be a better guide than available special techniques.