Dermatopathologic features of cutaneous squamous cell carcinoma and actinic keratosis: Consensus criteria and proposed reporting guidelines.

BACKGROUND: There is considerable variation in the literature regarding the dermatopathologic diagnostic features of and reporting guidelines for actinic keratosis (AK) and cutaneous squamous cell carcinoma (cSCC). OBJECTIVE: To develop consensus recommendations regarding diagnostic criteria, nomenclature, and reporting of AK and cSCC. METHODS: Literature review and cross-sectional multiround Delphi process including an international group of expert dermatopathologists followed by a consensus meeting. RESULTS: Consensus was achieved regarding the key dermatopathologic features necessary for diagnosing cSCC, AK, and associated variants; grading of degree of cellular differentiation in cSCC; utility of immunohistochemistry for diagnosis of cSCC; and pathologic features that should be reported for cSCC and AK. LIMITATIONS: Consensus was not achieved on all questions considered. CONCLUSION: Despite the lack of clarity in the literature, there is consensus among expert dermatopathologists regarding diagnostic criteria and appropriate reporting of AK and cSCC. Widespread implementation of these consensus recommendations may improve communication between dermatopathologists and clinicians, facilitating appropriate treatment of AK and cSCC.

Cutaneous atypical fibroxanthoma with osteoclast-like giant cell: A rare phenomenon.

Atypical fibroxanthoma (AFX) with osteoclast-like giant cells is a rare entity. We present the case of an elderly woman who presented with a pink-purple dome-shaped nodule with central hyperkeratotic crust. Biopsy revealed a cellular, dermal-based tumor comprised of spindle, oval, and osteoclast-like giant cells with pleomorphism. The immunohistochemistry profile supported a diagnosis of AFX with osteoclast-like giant cells. We performed a literature review through PubMed and Google Scholar for AFX with osteoclast-like giant cell formation and found 16 previously reported cases. We aim to provide a review and discuss features of these cases. We also discuss the pathogenesis of these osteoclast-like cells as well as potential pitfalls in diagnosis.

A Second Case of Localized Cutaneous Amyloid Elastosis: Expanding the Discussion of Associations With a Unique Histopathologic Entity.

ABSTRACT: Amyloid elastosis is an exceedingly rare form of amyloidosis characterized by amyloid material deposited on dermal elastic fibers. Most reported cases have been associated with systemic amyloid light-chain amyloidosis. A single previously reported case of amyloid elastosis showed evidence that the amyloid material was derived from light-chain proteins and was associated with a monoclonal plasma cell infiltrate but failed to demonstrate systemic involvement. As a result, the case was felt to represent localized cutaneous amyloid elastosis. We present a case of localized cutaneous amyloid elastosis that is not associated with a definitive monotypic plasma cell population or with systemic amyloidosis. We also review the clinical and histopathologic features of reported cases of amyloid elastosis and discuss possible etiologic considerations. Because amyloid elastosis can be either localized to the skin or associated with systemic involvement, additional workup to exclude an underlying plasma cell dyscrasia or hematologic malignancy is warranted.

Efficacy, rate of tumor response, and safety of a short course (12-24 weeks) of oral vismodegib in various histologic subtypes (infiltrative, nodular, and superficial) of high-risk or locally advanced basal cell carcinoma, in an open-label, prospective case series clinical trial.

BACKGROUND: Vismodegib demonstrated 60% response rates in the ERIVANCE trial. Basal cell carcinoma has various histopathologies. Their effect on response is unclear. OBJECTIVE: The purpose of this study was to determine whether basal cell carcinoma histopathology affected vismodegib response. METHODS: This phase 2b, single-center, prospective case series study compared the efficacy of vismodegib in infiltrative, nodular, and superficial basal cell carcinomas treated for 12 or 24 weeks in 27 patients. Patients had 1 target lesion and up to 3 nontarget lesions. RESULTS: Twenty-seven patients were enrolled, with 65 tumors (27 target lesions/38 nontarget lesions). At 24 weeks, most basal cell carcinomas achieved histologic clearance, with positive biopsy results in 10.5% of target lesions, 30.4% of nontarget lesions, and 21.4% overall. No statistical differences were observed between histopathologic subtypes. One hundred percent of patients experienced an adverse event, 94% grade 1 or 2. The most common adverse events were dysgeusia/loss of taste (86%), muscle spasms (82%), and alopecia (71%). Clinically progressive disease during treatment was low (1.5%). Two patients had recurrence within 1 year of treatment. LIMITATIONS: Limitations included sample size of basal cell carcinoma histopathologic subtypes, sampling punch biopsies, and short follow-up. CONCLUSIONS: Basal cell histopathologic subtype did not significantly affect response to vismodegib. Each subtype was observed to completely respond at 12 weeks of therapy, 24 weeks, or both.

Cutaneous intestinal metaplasia: An unusual cause of peristomal complication with malignant potential.

Peristomal ulcer with cutaneous intestinal metaplasia, defined by scattered colonic crypts within variably intact epidermis, is an exceedingly rare pathologic diagnosis, which possesses the potential to progress to primary adenocarcinoma. Herein, we report the third case of cutaneous intestinal metaplasia in a peristomal ulcer and emphasize the importance of diagnosis and surveillance when managing this rare entity.

Appropriate use criteria in dermatopathology: Initial recommendations from the American Society of Dermatopathology.

BACKGROUND: Appropriate use criteria (AUC) provide physicians guidance in test selection, and can affect health care delivery, reimbursement policy, and physician decision-making. OBJECTIVES: The American Society of Dermatopathology, with input from the American Academy of Dermatology and the College of American Pathologists, sought to develop AUC in dermatopathology. METHODS: The RAND/UCLA appropriateness methodology, which combines evidence-based medicine, clinical experience, and expert judgment, was used to develop AUC in dermatopathology. RESULTS: With the number of ratings predetermined at 3, AUC were developed for 211 clinical scenarios involving 12 ancillary studies. Consensus was reached for 188 (89%) clinical scenarios, with 93 (44%) considered "usually appropriate" and 52 (25%) "rarely appropriate" and 43 (20%) having "uncertain appropriateness." LIMITATIONS: The methodology requires a focus on appropriateness without comparison between tests and irrespective of cost. CONCLUSIONS: The ultimate decision to order specific tests rests with the physician and is one where the expected benefit exceeds the negative consequences. This publication outlines the recommendations of appropriateness-the AUC for 12 tests used in dermatopathology. Importantly, these recommendations may change considering new evidence. Results deemed "uncertain appropriateness" and where consensus was not reached may benefit from further research.

Muir-Torre syndrome appropriate use criteria: Effect of patient age on appropriate use scores.

BACKGROUND: Muir-Torre syndrome (MTS) is a rare inherited syndrome, with an increased risk of sebaceous and visceral malignancy. Prior reports suggest screening for mismatch repair (MMR) deficiency may be warranted in patients <50 years and when sebaceous neoplasms are located on a non-head and neck location. Previously, appropriate use criteria (AUC) were developed for clinical scenarios in patients >60 years concerning the use of MMR protein immunohistochemistry (MMRP-IHC). This analysis explores the appropriateness of testing in patients ≤60 years. METHODS: Panel raters from the AUC Task Force rated the use of MMRP-IHC testing for MTS for previously rated scenarios with the only difference being age. RESULTS: Results verify the previously developed AUC for the use of MMRP-IHC in neoplasms associated with MTS in patients >60 years. Results also show that in patients ≤60 years with a single sebaceous tumor on a non-head and neck site, MMRP-IHC testing should be considered. Testing can also be considered with a 2-antibody panel on periocular sebaceous carcinoma in younger patients. CONCLUSIONS: Our findings align with known evidence supporting the need to incorporate clinical parameters in identifying patients at risk for MTS, with age being a factor when considering MMRP-IHC testing.

Pigmented basal cell carcinoma: increased melanin or increased melanocytes?

BACKGROUND: Studies on the precise cause of increased melanization in pigmented basal cell carcinomas (BCC) are limited. We aimed to determine whether the cause of melanization is from increased number of melanocytes or increased melanin pigment, and if there is a difference in the number of melanocytes on different sun-exposed locations. METHODS: A retrospective review of 45 skin biopsies from January 2011 to February 2011 was performed; 30 were diagnosed as pigmented BCC and 15 as non-pigmented BCC. Immunohistochemistry for MART-1 (melanoma-associated antigen recognized by T-cell 1)/Melan-A (clone M2-7610 + M2-9E3; Leica Microsystems Inc. Buffalo Grove, IL, USA) from Biocare Medical (Concord, CA, USA) was performed on all biopsies. Associations between histopathologic features, number of melanocytes, location, and specific diagnoses were analyzed by Mann-Whitney U test. RESULTS: The mean melanocyte count per high powered field in pigmented BCCs from sun-exposed skin was 101.9 and from intermittently sun-exposed skin was 122.5, as compared to the controls (nodular non-pigmented BCC) of 27.4 (p = 0.002) and 34.9 (p = 0.002), respectively. CONCLUSIONS: Pigmented BCCs have a higher mean melanocyte count as compared to non-pigmented BCCs irrespective of location. Therefore, the pigment is not only due to increased melanin, but also due to increased melanocytes.

Diagnostic utility of SOX11 immunohistochemistry in differentiating cutaneous spread of mantle cell lymphoma from primary cutaneous B-cell lymphomas.

BACKGROUND: Mantle cell lymphoma (MCL) is associated with the worst prognosis among low-grade B-cell lymphomas. While cutaneous involvement by nodal or systemic MCL is uncommon, its differentiation from primary cutaneous B-cell lymphoma (CBCL) or cutaneous involvement by other extra-cutaneous BCL is challenging as neither histomorphology nor immunophenotype can be absolutely specific. We analyzed the diagnostic utility of SOX11 immunohistochemistry in differentiating secondary cutaneous MCL from other low-grade CBCL. METHODS: Immunohistochemical staining with anti-SOX11 antibody was performed on 8 cases of secondary cutaneous MCL, 16 secondary cutaneous CLL, 20 primary cutaneous MZL, 12 cutaneous FCL (6 primary, 6 secondary), 7 primary cutaneous DLBCL, leg type, 5 systemic DLBCL and 3 B-ALL. SOX11 and cyclin D1 staining were compared in secondary cutaneous MCL. RESULTS: Nuclear SOX11 staining was seen in seven of eight cases (88%) of secondary cutaneous MCL, including a case with minimal cyclin D1 expression. All other CBCL lacked detectable nuclear SOX11 expression. The sensitivity and specificity for SOX11 in MCL were 87.5 and 100%, respectively. Both the sensitivity and specificity for combined SOX11 and cyclin D1 immunohistochemistry were 100%. CONCLUSION: SOX11 immunohistochemistry could be a useful adjunct in distinguishing secondary cutaneous MCL from other CBCL.

Cutaneous mantle cell lymphoma: a clinicopathologic review of 10 cases.

Cutaneous mantle cell lymphoma (MCL) is exceedingly rare, almost always occurring as a dissemination of systemic MCL. To date, only 32 cases have been described. We report a series of 10 cases of MCL in the skin, and provide a comprehensive clinicopathologic review with clinical follow-up. Our cases occurred in older individuals (mean age = 70) and were more frequently in men (90%). Half of them presented in the head and neck region as a mass/nodule, and the remainder in the trunk and extremities as nodules. All patients have stage IV disease. In two of the 10 cases (20%) the cutaneous lesions preceded the diagnosis of disseminated disease. In two of the seven cases with available clinical follow-up information (33%) the skin was immediately involved after the diagnosis of MCL, and in three of the seven the skin was the first site of recurrence (mean interval = 57 months). The mean time to recurrence of the disease was 45.4 months and the overall survival was 66.3 months. Histologically six out of 10 cases (60%) had either pleomorphic or blastoid morphology (four out of 10 and two out of 10, respectively). The mean number of mitoses per 10 high-power fields was 18.44. While nine out of 10 cases expressed cyclin-D1, one case was not positive for cyclin-D1 but did label with SOX-11. Limited cytogenetic data showed trisomy 14 in one case, in addition to the t(11;14) translocation.

A Yellow Papular Eruption on the Arms, Legs, and Neck: A Rare Masquerader.

A 54-year-old Caucasian woman with a medical history of mitral valve prolapse presented with a 5-year history asymptomatic papules. There was no family history of similar lesions. Physical examination revealed >100, 2- to 4-mm, firm, yellow, dermal papules located on the neck, antecubital and popliteal fossae, flexor surface of both forearms, and inner aspect of the thighs (Figure 1). There was no skin laxity. A 4-mm punch biopsy was obtained from the left thigh for histologic examination. Findings showed a focal increase in the concentration of elastic fibers highlighted by Verhoeff Van Gieson stain (Figure 2). There was no fragmentation, calcification, or phagocytosis of elastic fibers. There was also no evidence of actinic elastosis. A section stained with hematoxylin and eosin appeared relatively unremarkable. These findings were consistent with late-onset focal dermal elastosis.

Clinical Practice Guidelines for Cutaneous Lymphomas.

Primary cutaneous lymphomas are non-Hodgkin lymphomas, which are broadly divided into cutaneous T-cell lymphomas and cutaneous B-cell lymphomas. These classifications include numerous distinct entities, all with varying clinical presentations and disease courses. Herein, we will review the cutaneous T-cell lymphomas, including Mycosis Fungoides, Sézary syndrome, CD30+ lymphoproliferative disorders, as well as other less common entities. Cutaneous B-cell lymphomas will also be discussed, including primary cutaneous marginal zoned lymphoma, cutaneous follicle-center lymphoma, diffuse large B-cell lymphoma, leg type, as well as other less common entities. Accurate and early diagnosis is key, as the treatment and prognosis varies significantly between conditions.

Prominent follicular mucinosis with diffuse scalp alopecia resembling alopecia areata.

A 56-year-old Caucasian female presented with a 2-month history of alopecia. On examination, she had diffuse hair loss of her scalp with some discrete patches of nonscarring alopecia. Histopathology revealed an inflammatory nonscarring alopecia with prominent follicular mucinosis and findings suggestive of alopecia areata. The patient's alopecia completely resolved with oral prednisone. The histopathologic findings and clinical presentation are most consistent with a diagnosis of alopecia areata with follicular mucinosis, although the differential diagnosis is broad. As follicular mucinosis may be associated with both benign and malignant conditions, it is important to be cautious regarding the clinical diagnosis when this reaction pattern is observed histopathologically.

Cutaneous myeloid sarcoma: natural history and biology of an uncommon manifestation of acute myeloid leukemia.

We conducted a retrospective study of patients with cutaneous myeloid sarcoma, from 2 tertiary care institutions. Eighty-three patients presented, with a mean age of 52 years. Diagnosis of myeloid sarcoma in the skin was difficult due to the low frequency of myeloperoxidase and/or CD34+ cases (56% and 19% of tested cases, respectively). Seventy-one of the 83 patients (86%) had ≥ 1 bone marrow biopsy. Twenty-eight (39%) had acute myeloid leukemia with monocytic differentiation. Twenty-three had other de novo acute myeloid leukemia subtypes. Thirteen patients had other myeloid neoplasms, of which 4 ultimately progressed to an acute myeloid leukemia. Seven had no bone marrow malignancy. Ninety-eight percent of the patients received chemotherapy, and approximately 89% died of causes related to their disease. Cutaneous myeloid sarcoma in most cases represents an aggressive manifestation of acute myeloid leukemia. Diagnosis can be challenging due to lack of myeloblast-associated antigen expression in many cases, and difficulty in distinguishing monocyte-lineage blasts from neoplastic and non-neoplastic mature monocytes.

New-onset vitiligo during long-term, stable infliximab treatment of pityriasis rubra pilaris.

Incidents of new-onset vitiligo attributed to infliximab therapy for rheumatoid arthritis and ulcerative colitis have been reported. Reported cases share a common theme in that symptoms manifested in close proximity to the initiation or significant dose increase of the medication. This case describes the presentation of infliximab-induced vitiligo in a patient using it for long-term treatment of stable pityriasis rubra pilaris. The patient was initiated and titrated to a stable dose of infliximab totaling 27 months' duration. He was able to achieve near-complete resolution of symptoms before developing depigmented patches consistent with vitiligo. Infliximab was discontinued. Tacrolimus 0.1% ointment and narrow-band ultraviolet B light successfully repigmented the patches. The association of discontinuing infliximab and resolution of vitiligo suggests infliximab had a role in this case. Though the mechanism of involvement is undetermined, infliximab may have induced an autoimmune process by paradoxically activating lymphocytes. Alternatively, infliximab antibodies may have led to the process by disrupting the normal balance of cytokines.