Diagnostic utility of the 23-gene expression profile test for an atypical intradermal melanocytic proliferation.

Ancillary tests such as immunohistochemistry (IHC) and gene expression profile (GEP) testing may be needed to arrive at a definitive diagnosis for some atypical melanocytic neoplasms. A 34-year-old male with a family history of melanoma presented with a large, heterogeneous melanocytic lesion on the cheek. Histopathological review of two biopsies revealed an atypical intradermal melanocytic proliferation with spitzoid features without ulceration or regression. Scattered mitotic figures were identified. In addition to performing SOX10 IHC, PRAME and HMB45 staining highlighted weak, patchy positivity that was stronger in superficial, pleomorphic melanocytes (Ki-67, 5-7% mitotic rate). Based on these concerning but ambiguous IHC results and lingering concern for melanoma reiterated by other consulting dermatopathologists, the 23-GEP was requested for both specimens, which both returned a malignant result. The inconclusive histopathological features of malignancy were resolved by 23-GEP testing, facilitating a final diagnosis of malignant melanoma (pT3a, 2.5 mm Breslow depth, Clark's level IV).

A retrospective study for association between post-transfusion hemoglobin S level and pre-transfusion hemoglobin S level at the next scheduled transfusion.

BACKGROUND: Patients with sickle cell disease (SCD) frequently undergo prophylactic red blood cell (RBC) exchange transfusion and simple transfusion (RCE/T) to prevent complications of disease, such as stroke. These treatment procedures are performed with a target hemoglobin S (HbS) of ≤30%, or a goal of maintaining an HbS level of <30% immediately prior to the next transfusion. However, there is a lack of evidence-based instructions for how to perform RCE/T in a way that will result in an HbS value <30% between treatments. PRINCIPAL OBJECTIVE: To determine whether targets for post-treatment HbS (post-HbS) or post-treatment HCT (post-HCT) can help to maintain an HbS <30% or <40% between treatments. MATERIALS AND METHODS: We performed a retrospective study of patients with SCD treated with RCE/T at Montefiore Medical Center from June 2014 to June 2016. The analysis included patients of all ages, and data including 3 documented parameters for each RCE/T event: post-HbS, post-HCT, and follow-up HbS (F/u-HbS), which is the pre-treatment HbS prior to the next RCE/T. Generalized linear mixed model was used for estimating the association between post-HbS or post-HCT levels and F/u-HbS <30%. RESULTS: Based on our results, targeting post-HbS ≤10% was associated with higher odds of having events of F/u-HbS <30% between monthly treatments. Targeting post-HbS ≤15% was associated with higher odds of events of F/u-HbS < 40%. As compared to post-HCT ≤30%, a post-HCT >30%-36% did not contribute to more F/u-HbS <30% or HbS <40% events. CONCLUSIONS: For patients with SCD undergoing regular RCE/T for stroke prevention, a post-HbS ≤10% can be used as a goal to help maintain an HbS <30% for 1 month, and a post-HbS ≤15% allowed patients to maintain HbS <40%.

A Physician's Guide to the Use of Gene Expression Profile Ancillary Diagnostic Testing for Cutaneous Melanocytic Neoplasms.

Objectives: Some melanocytic neoplasms suspicious for melanoma require additional workup to arrive at a final diagnosis. Within the last eight years, gene expression profiling (GEP) has become an important ancillary tool to aid in the diagnosis of melanocytic neoplasms with uncertain malignant potential. As the usage of two commercially available tests (23-GEP and 35-GEP) evolves, it is important to answer key questions about optimal utilization and their impact on patient care. Methods: Recent and relevant articles answering the following questions were included in the review. First, how do dermatopathologists synthesize the available literature, the latest guidelines, and their clinical experience to determine which cases would be most likely to benefit from GEP testing? Second, how best can a dermatologist convey to their dermatopathologist that the use of GEP in the diagnostic process could provide a more clearly defined result and thereby help empower the dermatologist to provide higher-quality patient care when making specific patient management decisions for otherwise pathologically ambiguous lesions? Results: When interpreted in the context of the clinical, pathologic, and laboratory information, GEP results can facilitate the rendering of timely, accurate, and definitive diagnoses for melanocytic lesions with otherwise uncertain malignant potential to inform personalized treatment and management plans. Limitations: This was a narrative review focused on clinical use of GEP compared to other ancillary diagnostic tests performed postbiopsy. Conclusion: Open communication between dermatopathologists and dermatologists, especially regarding GEP testing, can be a vital component to achieve appropriate clinicopathologic correlation for otherwise ambiguous melanocytic lesions.

Superficial solitary fibrous tumor masquerading as a dermoid cyst: a case report.

Background: Solitary fibrous tumors (SFTs) are relatively rare spindle cell neoplasms uncommonly seen in dermatology practice. Initially discovered as a pleural tumor, SFTs have also been found in extra-pleural sites including the skin and soft tissues. When arising within the dermis or subcutis they are termed superficial SFTs, where they often present as solitary, unilateral, slow growing superficial masses. Histologically, they are composed of spindle cells arranged in a "patternless" pattern with hemangiopericytoma-like vessels dispersed throughout. Historically, CD34, CD99 and Bcl-2 immunohistochemical (IHC) stains were used to differentiate SFTs from other spindle cell neoplasms, however these markers are not entirely specific. Recent discovery of a disease defining NGFI-A binding protein 2 (NAB2)-signal transducer and activator of transcription 6 (STAT6) fusion gene has led to the use of STAT6 IHC staining to help verify the diagnosis of SFTs, particularly in unexpected sites. Case Description: We report a case of a 23-year-old woman with a slowly growing lateral supra-orbital mass, clinically concerning for a dermoid cyst, which was subsequently discovered to be a SFT on pathologic examination, with the diagnosis being verified by STAT6 immunostaining. Conclusions: SFTs are rarely encountered in dermatologic practice, however, must be kept on the differential of subcutaneous nodules, including those occurring in young adults. Due to the rarity of these tumors in clinical practice, a proposed algorithm for the approach to management of SFTs is included, guided by a validated, histology-driven, metastatic risk assessment tool, to help guide other clinicians confronted by these tumors.

A Case of Indeterminate Cutaneous Dendritic Cell Tumors in the Setting of Chronic Myelomonocytic Leukemia.

ABSTRACT: Chronic myelomonocytic leukemia (CMML) is a rare hematopoietic stem cell neoplasm. Indeterminate dendritic cell neoplasm (IDCN) is an extraordinarily rare histiocytosis that may manifest secondarily to CMML. A 75-year-old man with a 2-year history of CMML presented for multiple cutaneous lesions on his head and neck. Biopsy results yielded a dense diffuse infiltrate of large pleomorphic cells, which were positive for CD1a, S100, and CD56 with weak positivity for CD43 and CD68. Given his history of CMML, the patient was diagnosed with IDCN. This may indicate a progression of his CMML or transformation to acute leukemia; therefore, a systemic workup was recommended. IDCN may manifest secondary to a wide number of hematopoietic malignancies, with CMML being a rare occurrence. Recorded responses to phototherapy are reassuring, whereas systemic therapy may be appropriate for widespread cases. Remaining vigilant for cutaneous changes in patients with CMML will help prevent misdiagnosis and encourage prompt initiation of appropriate treatment.

Collision of Basal Cell Carcinoma and Sebaceous Carcinoma Extirpated With Mohs Micrographic Surgery.

Collision tumors are neoplasms composed of two or more distinct cellular lineages coexisting at the same anatomic site. Incomplete biopsy, partial pathological slide examination or failure to include this diagnosis into the clinical differential may complicate and delay appropriate therapy. Although collision tumors are well documented, basal cell carcinoma (BCC) occurring with sebaceous carcinoma (SC) has only been reported in a single case report. The aim of the authors is to present a case of collision BCC and SC to highlight a rare clinicopathological case. We also present this case to advise caution to detect mimickers of BCC that warrant greater clinical workup and use this case to emphasize the importance of Mohs micrographic surgery for the treatment of SC.

Primary cutaneous perivascular epithelioid cell tumors: two cases and a review of the literature.

Report _Case Presentation _Photo Vignette _Letter Authors declare that the contents of this article are their own original unpublished findings. Title: Primary cutaneous perivascular epithelioid cell tumors: two cases and a review of the literature Authors: Jennifer Wong1 DO, Jason Mammino2 DO, Jennifer Seyffert3 DO, Kristen Schmits4 MD, Etan Marks4 MD, Daniel Rivlin3 MD Affiliations: 1Department of Dermatology, LECOM- Larkin Community Hospital, Miami, Florida, USA, 2Department of Dermatology, KCUMB - Advanced Dermatology and Cosmetic Surgery, Orlando, Florida, USA, 3Department of Dermatology, LECOM- Skin and Cancer Associates, Miami Beach, Florida, USA, 4Department of Dermatopathology Advanced Dermatology and Cosmetic Surgery Pathology Laboratory, Delray Beach, Florida, USA Corresponding Author: Jennifer Seyffert DO, 4308 Alton Road, Suite 510, Miami Beach, FL 33140, Tel: 305-674-8865, Fax: 305-674-1459, Email: jseyf12@gmail.com Abstract: Perivascular epithelioid cell tumors, also known as PEComas, are mesenchymal neoplasms which uncommonly originate within the skin, with only 23 cases documented within the literature. These rare neoplasms classically display epithelioid cells composed of granular or clear cytoplasm arranged in sheets, nests, or cords. Their immunoreactivity for melanocytic and smooth muscle markers makes these tumors distinct and unique.[1] We herein present two cases of primary cutaneous PEComas that clinically mimic other common cutaneous neoplasms and illustrate the necessity for clinical-pathologic correlation. A literature review is also presented to compare the different clinical and histological presentations of cutaneous PEComas.

How to Succeed in Fellowship Acquisition: A Survey of Pathology Residents.

Medical school curricula limit students' exposure to pathology practice while pathology subspecialty training programs require residents to apply for fellowships as early as the end of their first year of training. Thus, limited exposure to pathology practice creates significant confusion and anxiety, often making the fellowship application process premature. Additionally, early focus on subspecialty training in order to acquire a fellowship adds to the initial lack of emphasis on general pathology training. We prepared a voluntary online survey with questions developed through focus groups and advice from an expert in survey design to determine which fellowships are desired and how successful residents are in their pursuit of these fellowships. The survey was distributed through the Pathology Residency Program Directors' (PRODS) listserv. Answers were solicited from pathology trainees throughout the entire training cycle. There were 141 (4.6% response rate) total respondents with each postgraduate year represented. One hundred twenty-two (95%) of 129 residents plan on completing 1 or 2 fellowships after residency training. Encouragingly, 94 (75%) of 126 pathology residents attained their desired specialty fellowship. However, 32 (32%) of 99 residents who acquired at least one fellowship chose a general surgical pathology fellowship. Furthermore, 33 (24%) respondents had already decided to pursue a specific specialty while still in medical school. An additional 32 (23%) came to their decision during postgraduate year 1. Therefore, although most residents are successful in attaining their desired fellowship, further research is needed to understand the effect of early commitment to a subspecialty and its impact on pathology education.

Two cases of phenotypic switch of primary cutaneous T cell lymphoma after treatment with an aggressive course and review of the literature.

A "phenotypic switch" (PS) is a well-known phenomenon that occurs in hematopoietic neoplasms, often after treatment. However, in cutaneous T cell lymphoma (CTCL), this event has rarely been reported, and thus, very little is known about its relevance to disease prognosis. We report two cases of patients that were diagnosed with a CD4+ mycosis fungoides with positive T cell receptor gene rearrangement studies. Both patients originally responded to treatment, but subsequently, their CTCL came back with a different phenotype of a CD4- CTCL. Gene rearrangement studies were performed on the second occurrence in order to prove that this was the same lymphoma. Both patients died from their CTCL. Additionally, we collected seven cases of primary CTCL from the literature with tissue samples from before and after treatment with molecular studies confirming these neoplasms contained the same T cell clone, providing evidence of a true PS. This too revealed a poor prognosis in the majority of these cases. CTCL should be worked up to determine whether a PS has occurred after therapy since it could confuse management of patients and appears to portend a poor prognosis.

Refractory macrophage activation syndrome in the setting of adult-onset Still disease with hemophagocytic lymphohistiocytosis detected on skin biopsy treated with canakinumab and tacrolimus.

A 19-year-old Caucasian female with adult-onset Still disease (AOSD) presented for evaluation of an acute clinical decompensation and atypical annular papules and plaques with purpura on the lower extremities. A punch biopsy demonstrated histiocytes with engulfed degenerated erythrocytes and lymphocytes, consistent with hemophagocytic lymphohistiocytosis (HLH). HLH, clinically referred to as macrophage activation syndrome, is a rare complication of AOSD and is life-threatening. Relevant clinical, laboratory, and histologic features of this diagnosis are reviewed.

Specific TCR gene rearrangements in mycosis fungoides: does advanced clinical stage show a preference?

AIMS: The relationship between the presence of specific T-cell receptor (TCR) gene rearrangements and clinical stage in mycosis fungoides (MF) has not been studied. We analysed a cohort of patients with a diagnosis of MF to determine the different types of specific TCR gene rearrangements present and their relationship to disease stage. METHODS: A retrospective chart review was used to select patients with a diagnosis of MF who had a skin biopsy and a positive TCR gene rearrangement study in either blood or tissue and at least 2 years of clinical follow-up. RESULTS: 43 patients were identified and divided into two groups. The first group consisted of 23 patients with early stage disease (IA-IIA) that was either stable or went into partial or complete remission with minimal intervention. None of these patients advanced to late stage disease. The second group consisted of 20 patients who had either late stage disease at diagnosis or progressed to late stage disease at some point in time. In the first group, only 4/23 (17%) patients had a single TCR gene rearrangement in the VÉ£1-8 region. In contrast, the second group had 13/20 (65%) patients with a single TCR gene rearrangement in the VÉ£1-8 region (p=0.002). CONCLUSION: The presence of a single TCR gene rearrangement in the VÉ£1-8 region could possibly be related to a more advanced stage of MF. However, more comprehensive studies, such as next generation sequencing, with a larger cohort is necessary for a more definitive conclusion.

Livedoid Vasculopathy Presenting in a Patient With Sickle Cell Disease.

We report a case in which a 43-year-old African American male with medical history of sickle cell disease (SCD) presented with a nonhealing ulcer. Biopsy revealed features of livedoid vasculopathy. Previously, livedoid vasculopathy had only been described in a patient with sickle cell trait, but never in a patient with SCD. Livedoid vasculopathy most commonly affects the distal lower extremities and is characterized by irregular, punched-out, painful ulcers that heal with stellate white scars of atrophie blanche. Histologically, it reveals segmental hyalinizing vessels, focal thrombosis, and endothelial proliferation. The etiology is currently unclear, but it has been shown to be related to procoagulant states and a diagnosis of livedoid vasculopathy should prompt a thorough hypercoagulable workup, including testing for SCD in high-risk patients.

Duodenal-Type Follicular Lymphoma: A Clinicopathologic Review.

Duodenal-type follicular lymphoma (D-FL) is a newly recognized entity in the 2016 World Health Organization classification update. It has an immunophenotype similar to that of other FLs and usually carries the typical t(14;18)(q32;q21) translocation. However, unlike other FLs, D-FL is almost always diagnosed at a low stage and stays localized to the small intestine, most commonly the second portion of the duodenum, whereas the vast majority of other FLs are diagnosed at an advanced stage. Additionally, D-FL gene expression and pathogenesis appear to be more closely related to extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue than to other types of FL. Therefore, many oncologists have opted to treat this variant of FL in a "watch and wait" manner because of its excellent prognosis and the rarity of D-FL to progress even when no treatments are attempted.

Impact of Prothrombin Complex Concentrate on Blood Use, Cost, and Outcomes in Heart Transplantation.

BACKGROUND: Left ventricular assist device (LVAD) recipients undergoing heart transplantation have increased bleeding risk. We compared conventional warfarin reversal with fresh frozen plasma vs 4-factor prothrombin complex concentrate (PCC) and the effect on transfusion requirements, blood bank costs, and clinical outcomes. METHODS: A retrospective review identified 60 consecutive LVAD recipients undergoing heart transplantation divided into two groups: 30 (no PCC) received fresh frozen plasma and 30 (PCC) received PCC. Patient characteristics, intraoperative and postoperative transfusion requirements, short-term clinical outcomes, and blood bank costs were compared. PCC association with transfusion requirements was assessed by multivariate linear regression. RESULTS: Patients who received PCC were younger (50 ± 11 vs 57 ± 13 years, p = 0.02), fewer had ischemic cardiomyopathy (23% vs 60%, p = 0.01), had more than one prior sternotomy (7% vs 30%, p = 0.04), and had higher preoperative hemoglobin (11.8 ± 1.8 vs 10.4 ± 1.8 g/dL, p = 0.01). The PCC group had a significantly shorter bypass time (185 vs 217 minutes, p = 0.01), received less fresh frozen plasma (2 vs 5 units, p = 0.03), cryoprecipitate (0 vs 2 units, p = 0.05), and total blood products (9 vs 13.5 units, p = 0.03) intraoperatively, and was less likely to require delayed sternal closure (3% vs 23%, p = 0.05). On multivariate linear regression, PCC was significantly associated with decreased intraoperative transfusion (ß = -6.09, p = 0.02). There was no difference in thromboembolic events or in-hospital death. Total blood bank costs were $4,949 for PCC and $3,677 for no PCC (p = 0.01). CONCLUSIONS: Although more costly, PCC reduced transfusion requirements and delayed sternal closure in heart transplant recipients bridged with LVAD, justifying its use over traditional warfarin reversal.

Did I Miss It? Discovering Hidden Coexisting Hematological Neoplasms: A Single Institutional Review of 100 Collision Tumors.

A collision tumor is defined as two histologically distinct tumor types identified at the same anatomic site. Hematolymphoid proliferative disorders (HLPDs), which coincide with non-hematological neoplasms, can mimic an immune response and can easily be overlooked as an immune reaction to a solid organ neoplasm, especially when low grade. In order to avoid a delay in the diagnosis of a HLPD during the workup for a non-hematological neoplasm, we identified a cohort of 100 cases with a HLPD diagnosis during the initial workup and treatment of a non-hematological neoplasm, or vice versa. Among the 100 collision tumors, the most common non-hematological neoplasms associated with a HLPD were from the colon (17%), breast (15%), and prostate (12%). The most commonly identified HLPDs were chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL; 18%), diffuse large B-cell lymphoma (17%), follicular lymphoma (14%), marginal zone lymphoma (10%), acute myeloid leukemia (8%), and classical Hodgkin lymphoma (5%). Interestingly, in this cohort 5% of the low-grade HLPDs, all of them CLL/SLL, were missed at initial sign-out and subsequently required an addendum report. The other 95% of cases were reviewed or signed out by a hematopathologist before the report was finalized for the non-hematological neoplasm. In summary, high-grade hematological malignancies are less likely to be missed; however, low-grade coexisting HLPDs can be overlooked as a reactive immune response to a solid organ neoplasm. Therefore, it is important to keep in mind the existence of collision low-grade HLPDs before assuming the lymphoid infiltrates as an immunological response.

CD117 (KIT) is a useful marker in the diagnosis of plasmablastic plasma cell myeloma.

AIMS: Plasmablastic plasma cell myeloma (PPCM) is a rare morphological presentation of multiple myeloma, and can resemble plasmablastic lymphoma (PBL), a human immunodeficiency virus (HIV)-related lymphoid neoplasm, morphologically and immunophenotypically. The aim of this study was to retrospectively search for factors that could help to differentiate these two entities. METHODS AND RESULTS: We used clinical looking glass, a data mining tool, to identify patients with a diagnosis of either PPCM or PBL with a CD117 test performed. We identified 27 cases from 16 patients in our institution with a diagnosis of either PPCM or PBL. There were 14 cases of PBL from eight patients and 13 cases of PPCM from eight patients. We found that six of eight patients with PPCM were positive for CD117, whereas no patients with PBL (0/8) showed positivity (P = 0.007 for patients). All (8/8) PPCM patients had a paraproteinaemia, whereas only two of eight PBL patients had a paraproteinaemia (P = 0.007). Lytic bone lesions were more indicative of a PPCM, with six of eight patients showing these lesions, and only one of eight PBL patients showing these lesions (P = 0.0406). HIV status was more likely to be positive in PBL patients, with six of seven patients showing positivity, and only one of five PPCM patients showing positivity (P = 0.072). Epstein-Barr virus-encoded RNA in-situ hybridization did not differentiate these two entities, with seven of eight PBL patients showing positivity, and two of five PPCM patients showing positivity (P = 0.2168). CONCLUSIONS: This study reveals that CD117 can be a useful marker to help differentiate PPCM from PBL and give the patient an appropriate prognosis and options for treatment.