Myelodysplasia Cutis.

CONTEXT.­: Myelodysplasia cutis is an emerging concept in cutaneous neoplasia. Many of these cases were previously included under the umbrella of histiocytoid Sweet syndrome. However, with the advent of next-generation sequencing, cutaneous involvement by myelodysplastic syndrome is being increasingly recognized. OBJECTIVE.­: To review histiocytoid Sweet syndrome and myelodysplasia cutis and discuss our current understanding of these entities. Additionally, to discuss how next-generation sequencing can be applied in the evaluation of cutaneous infiltrates of immature histiocytoid cells. DATA SOURCES.­: The English-language literature from 2005 to 2023 on the topic of histiocytoid Sweet syndrome and myelodysplasia cutis was reviewed. CONCLUSIONS.­: Biopsy specimens showing infiltrates of histiocytoid, immature myeloid cells may represent cutaneous involvement by myelodysplastic syndrome. Close clinical correlation is recommended in these cases. Recent studies suggest that next-generation sequencing is useful in separating myelodysplasia cutis from true histiocytoid Sweet syndrome. This distinction has important implications for patients.

The Antibiotic Trimethoprim Displays Strong Mutagenic Synergy with 2-Aminopurine.

We show that trimethoprim (TMP), an antibiotic in current use, displays a strong synergistic effect on mutagenesis in Escherichia coli when paired with the base analog 2-aminopurine (2AP), resulting in a 35-fold increase in mutation frequencies in the rpoB-Rifr system. Combination therapies are often employed both as antibiotic treatments and in cancer chemotherapy. However, mutagenic effects of these combinations are rarely examined. An analysis of the mutational spectra of TMP, 2AP, and their combination indicates that together they trigger a response via an alteration in deoxynucleoside triphosphate (dNTP) ratios that neither compound alone can trigger. A similar, although less strong, response is seen with the frameshift mutagen ICR191 and 2AP. These results underscore the need for testing the effects on mutagenesis of combinations of antibiotics and chemotherapeutics.

Angioimmunoblastic T-cell lymphoma mimicking diffuse large B-cell lymphoma.

Angioimmunoblastic T-cell lymphoma (AITL) is an aggressive form of peripheral T-cell lymphoma that is characterized by lymphadenopathy, night sweats, fever, weight loss, and autoimmune phenomena. Cutaneous manifestations are present in up to 50% of cases, but few cases are reported in the dermatologic literature. We present a case of AITL that manifested in the skin. The patient was diagnosed with diffuse large B-cell non-Hodgkin lymphoma 3 months prior based on results from a lymph node biopsy. Reexamination and immunohistochemical staining of the previously biopsied lymph node specimen revealed the same clonal population of T cells positive for CD3, CD4, CD10, and programmed cell death protein 1 (PD-1) that was present in the skin and confirmed a diagnosis of AITL. Angioimmunoblastic T-cell lymphoma is frequently misdiagnosed due to its nonspecific clinical and histologic findings; it is not uncommon for AITL to be mistaken for other types of lymphoma. Dermatologists and dermatopathologists can play an important role in the recognition of this difficult-to-diagnose malignancy.

Cryptococcal cellulitis: A rare entity histologically mimicking a neutrophilic dermatosis.

Cutaneous Cryptococcus infection presents classically with granulomatous and gelatinous reactive patterns. Cases mimicking neutrophilic dermatoses have not been described. Conversely, neutrophilic dermatoses with degrading cells mimicking cryptococcal organisms have been reported. We report a case of cryptococcal cellulitis in an immunocompromised male with a robust neutrophilic infiltrate raising histologic consideration for a neutrophilic dermatosis.

Primary cutaneous Epstein-Barr virus-positive diffuse large B-cell lymphoma: a rare and aggressive cutaneous lymphoma.

Cutaneous B-cell lymphomas represent a group of lymphomas derived from B lymphocytes in various stages of differentiation. The skin can be the site of primary or secondary involvement of any of the B-cell lymphomas. The classification of primary cutaneous B-cell lymphomas has evolved as the use of immunohistochemical and molecular genetic techniques have become more widespread. Primary cutaneous Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma (DLBCL) is a rare and aggressive cutaneous neoplasm with a more aggressive clinical course and poorer prognosis than most of the primary cutaneous B-cell lymphoma subtypes. Further research is needed to establish optimal treatment regimens for this aggressive cutaneous lymphoma. Although rare, EBV-positive DLBCL is an important entity to consider when evaluating a patient with a suspected primary cutaneous lymphoma.

Disseminated botryomycosis: a rare presentation.

Botryomycosis is a rare chronic bacterial infection of the skin or viscera that resembles a deep fungal infection. Botryomycosis has two distinct patterns of infection, visceral and cutaneous, the latter being the most common. Cutaneous botryomycosis typically appears as a solitary plaque with superficial pustules. Histologically, bacterial colonies are arranged in a distinctive "bunch of grapes" pattern with surrounding eosinophilia, known as the Splendore-Hoeppli phenomenon. Here we report a case of an 83-year-old female with disseminated botryomycosis.

A Case of a Cellular Neurothekeoma Presenting with Headaches and Review of the Literature.

A 12-year-old female presented with a 1-year history of a slow-growing lesion on the frontal scalp. The patient reported intermittent headaches increasing in frequency localized under the lesion. Physical exam revealed a firm, fixed, 5-mm orange-pink papule on the right frontal scalp. Excisional biopsy was performed using a 6-mm punch biopsy, after which the patient reported a cessation of headaches. Histopathology showed a diffuse proliferation of spindled and epithelioid cells within the superficial and deep reticular dermis demonstrating a nested as well as fascicular growth pattern. There was also focal myxoid dermal change. Immunohistochemical staining showed the tumor to be strongly positive for NK1C3 and negative for S-100. A diagnosis of cellular neurothekeoma was made. Cellular neurothekeomas are slow-growing, asymptomatic nodules that most frequently appear on the head and neck of young adults. Cellular neurothekeomas rarely present with symptoms beyond mild tenderness upon palpation. Our case represents a unique presentation of a neurothekeoma of the scalp with complaint of headaches, previously unpublished in the literature.

Cutaneous lupus erythematosus in a patient undergoing intravitreal bevacizumab injections: case report and review of the literature.

INTRODUCTION: Bevacizumab is a recombinant humanized antibody against vascular endothelial growth factor (VEGF). It is approved by the Food and Drug Administration (FDA) for metastatic colorectal cancer, advanced non-small cell lung cancer, metastatic renal cell cancer and glioblastoma. Bevacizumab has also been used off label in ophthalmology for age-related macular degeneration, diabetic retinopathy, retinal vein occlusions, retinopathy of prematurity, and other chorioretinal vascular disorders. Numerous case reports have described various cutaneous reactions in response to bevacizumab therapy including acneiform eruptions and exfoliative dermatitis. CASE PRESENTATION: We report a case of a 63 year-old Caucasian female who presented with subacute cutaneous lupus erythematosus six weeks after initiating two intravitreal injections of bevacizumab for central serous choroidopathy. CONCLUSION: We report the first documented case of a cutaneous lupus erythematosus eruption following bevacizumab administration as a monotherapy.

Expression of cyclooxygenase-2 and peroxisome proliferator-activated receptor gamma during malignant melanoma progression.

BACKGROUND: Cancer chemoprevention using nonsteroidal anti-inflammatory drugs is frequently attributed to cyclooxygenase-2 (COX-2) inhibition, although recent studies suggest that peroxisome proliferator-activated receptor gamma (PPARgamma) may also be involved. While surgical excision remains the treatment mainstay for localized malignant melanoma, certain high-risk patients may benefit from adjunctive chemotherapy. In this study, we compared COX-2 and PPARgamma immunohistological staining in benign nevi, primary melanomas and metastatic melanomas to help predict the effectiveness of compounds targeting these markers. METHODS: COX-2 and PPARgamma immunohistological staining was performed and reviewed in 99 melanocytic lesions, including 38 benign nevi, 32 primary melanomas and 29 metastatic melanomas. RESULTS: There was a significant increase in both COX-2 and PPARgamma immunostaining in melanomas compared with benign nevi. Metastatic melanomas were more likely to have a higher number of PPARgamma-immunopositive cells. They were also more likely to express COX-2 than primary melanomas. Neither COX-2 nor PPARgamma expression was associated with a specific pathologic subtype. CONCLUSIONS: COX-2 and PPARgamma may help modulate the progression of melanocytic precursor lesions to disseminated malignant melanoma. As such, they may serve as candidate substrates for targeted cancer therapies and may be particularly useful as adjuncts to surgery.

Cyclin D1 expression in melanocytic lesions of the skin.

BACKGROUND: Progression through the cell cycle is controlled by cyclins, cyclin-dependent kinases, and cyclin-dependent kinase inhibitory proteins. The role of cyclin D1 in the development and progression of melanomas is controversial. The goal of this study is to evaluate the role of cyclin D1 in benign and malignant melanocytic lesions of the skin. METHODS: A total of 126 pigmented lesions of the skin including compound nevi (21), intradermal nevi (18), melanoma in situ (28), primary invasive melanomas (30), and metastatic melanoma (29) were evaluated for cyclin D1 expression. The following tiered system was used for scoring: 0% nuclear staining (score 0), 1% to 19% nuclear staining (score 1), 20% to 49% nuclear staining (score 2), and 50% or greater nuclear staining (score 3). RESULTS: Average scores were significantly higher for primary melanomas compared with nevi and for in situ melanomas compared with primary invasive melanomas. The average score for metastatic melanomas was not significantly different compared with primary invasive melanomas. Scores for primary invasive melanomas did not correlate with depth of invasion or presence of metastases. Compound nevi exhibited a slightly higher level of cyclin D1 expression compared with intradermal nevi. CONCLUSION: Although primary melanomas show a higher level of cyclin D1 expression compared with nevi, cyclin D1 appears to have little role in development of a metastatic phenotype. It is not clear why lesions localized near the dermal-epidermal junction express higher levels of cyclin D1. Further studies are indicated to ascertain the biologic role and practical utility of cyclin D1 in melanocytic lesions of the skin.

Lymphangioma-like Kaposi sarcoma.

BACKGROUND: Lymphangioma-like Kaposi's sarcoma (LLKS) is a rare morphologic expression of Kaposi's sarcoma (KS) that occurs in virtually all of the well-recognized clinical subtypes of the disease and has the potential to mimic other pathologic processes. In this study, we present the clinical and pathological features of four patients with LLKS. METHODS: Four cases of LLKS were retrieved from the dermatopathology files of our institution. All four tumours were tested immunohistochemically with anti-human herpesvirus-8 (HHV-8) latent nuclear antigen-1 (LNA-1) and anti-CD34 antibodies. RESULTS: Clinically, each patient presented with violaceous patches, papules or plaques; one patient presented with bullous lesions. All of the LLKS biopsy specimens revealed areas with characteristic light microscopic features of KS. Lymphangioma-like foci consisted of ectatic, irregularly shaped vascular spaces lined by mildly atypical endothelial cells. All tumour cells, including those associated with LLKS foci, showed a strong and diffuse reactivity for anti-HHV-8 LNA-1 and anti-CD34. KS progressed slowly in two patients with adequate follow-up. CONCLUSIONS: As LLKS can mimic other disease processes, the correct diagnosis relies heavily on the recognition of salient clinical and histological features of conventional KS, including a strong immunohistochemical expression of HHV-8-associated LNA-1 in lesional cells.

Signet-ring cell change versus signet-ring cell carcinoma: a comparative analysis.

Signet-ring cell change (SCC) is a nonneoplastic condition that morphologically simulates signet-ring cell carcinoma (SRCA). The few case reports on SCC have focused on morphologic characteristics in distinguishing benign from malignant. In biopsy specimens, however, SCC can be easily confused with SRCA, which often demonstrates innocuous cytologic features. The object of this study is twofold: 1) to report 14 additional cases of SCC, comparing their morphologic and phenotypic features with that of SRCA; and 2) to evaluate the incidence of SCC in pseudomembranous colitis. Paraffin sections of biopsy or resection specimens containing focal or extensive SCC and 5 cases of colonic SRCA were stained with hematoxylin and eosin, periodic-acid Schiff stain with and without diastase digestion, and by standard ABC immunoperoxidase procedure using antibodies to E-cadherin, p53, and Ki-67. Both cells in SCC and SRCA were strongly positive for neutral mucins. Cells in SCC were strongly positive for E-cadherin and negative for p53 and Ki-67. In contrast, cells in SRCA were strongly positive for p53, exhibited high proliferation, and demonstrated absent or weak positivity for E-cadherin. Although SCC is not well recognized in pseudomembranous colitis, the incidence is fairly high: 14 of 50 (28%) cases showed variable numbers of signet-ring cells. Extensive SCC, although rare, can occur in different clinical conditions and can be easily mistaken for SRCA. When in doubt, routine immunohistochemical stains such as p53, Ki-67, and E-cadherin can help to differentiate SCC from SRCA.