Trichostasis Spinulosa of the Heel: Unique Presentation with Characteristic Morphology

Trichostasis Spinulosa is a peculiar lesion of the hair follicle that typically presents on the face. We present a case of a 59 years old Middle Eastern male who presented with a dark lesion on his heel. Examination revealed a 1.7 cm well-circumscribed black necrotic plaque with surrounding overhanging border with a differential diagnosis of melanoma. Histologically, the lesion was formed by inflamed clusters of numerous small hair shafts, consistent with Trichostasis Spinulosa of the heel. We report this case because of its unusual location and unique presentation

Mantle Cell Lymphoma Presenting as Diarrhea in a Liver Transplant Recipient

We present a 63-year-old man with a medical history of hepatocellular carcinoma who underwent orthotopic liver transplant 10 years prior on long-term immunosuppressive therapy. The patient presented to the clinic with diarrhea, and the workup revealed mantle cell lymphoma. Mantle cell lymphoma is an extremely rare finding in transplanted livers. It is essential to include mantle cell lymphoma, along with a broad differential, during the workup of diarrhea in post-transplant patients

Correlation of PD-L1 expression, clinicopathologic and molecular characteristics in an array of solid tumors: A large-scale real world study

Background: Programmed death ligand-1 (PD-L1) is a predictive marker of anti-programmed death protein 1 (PD- 1)/PD-L1 therapies for solid tumors. Limited literature exists correlating PD-L1 expression, clinicopathological & molecular profiles. We aimed to 1) correlate PD-L1 immunohistochemistry (IHC) results with these profile across multiple solid tumors & 2) assess clinical outcomes (overall survival (OS) & disease-free survival (DFS)) of PD-L1 status with / without anti-PD-L1 immunotherapy (IT). Design: All cases tested for PD-L1 IHC over 2 years (Aug 2019-Sep 2020) were retrieved for this study. Clinicopathological variables recorded included age, race, tumor type, type of PD-L1 clone, PD-L1 status (Tumor Proportion Score (TPS): negative:50%), Combined Positive Score (CPS): negative10), clinical stage, anti-PD-L1 IT. Microsatellite instability (MSI) status using IHC & Ploymerase chain reaction (PCR) assays was recorded. High PD-L1 was defined as PD-L1 expression of TPS \u3e50%/CPS\u3e10. Outcome studies included OS and DFS after generating Kaplan-Meier curves & compared using log rank test. Univariate analysis using Cox regression models were also used. Results: There were 205 cases tested for PD-L1 by IHC. Cohort included non-small cell lung cancers (127), head & neck carcinomas (37), gastric or gastroesophageal carcinoma (20), kidney or urothelial carcinoma (16), cervical carcinomas (5). Median age was 70 years (range 28-90). Most were high stage cancers [stage 1: 5/205, stage 2: 5/205, stage 3: 30/205, stage 4 165/205]. PD-L1 IHC clones included: 22C3 (152/205), 28-8 (21/205) & both (32/205). High PD-L1 expression was observed in 52/205 (25.3%), out of which [37/127 (29.1%) were adenocarcinoma, 13/54 (24%) were squamous cell carcinoma, 2/24 (4.1%) others]. Anti PD-L1 IT was given in 65/205 (31.7%) patients. Anti PD-L1 IT was significantly associated with longer median survival OS (p=0.015) & DFS (p=0.004) (Figure 1). PD-L1 status was significantly associated with OS (p=0. 034) but not DFS (p=0. 076) (Figure 1). High PD-L1 had shorter median survival and higher hazards of death in OS (HR=5.4, CI-1.3-23.1) irrespective of IT. Association between three groups of PD-L1 status when compared with IT was statistically significant (p=0.048, Figure 2). PD-L1 & MSI testing was available in 29 patients & did not show any statistical correlation in this small cohort. No significant difference in survival for those received IT (4/29) vs no IT (25/29) & tested for both PD-L1 & MSI (OS: p= 0.277, DFS: p= 0.107). Conclusions: This study supports the rational approach for PD-L1 therapy. High PD-L1 expression is more commonly seen in adenocarcinoma. Expression of high PD-L1 is associated with worse OS but not DFS. PD-L1 IT is significantly associated with longer median survival, OS & DFS. Larger, prospective studies are needed to support our findings

Salivary gland hyalinizing clear cell carcinoma with cutaneous metastasis: a rare and deceptive tumor

Clear cell carcinoma (CCC) is an uncommon malignant tumor of minor salivary glands. It characteristically has a low-grade morphology and a favorable outcome by most reports. An EWSR1-ATF1 fusion can be detected in the majority of cases. We present a rare case of CCC which had an aggressive course with the development of cutaneous metastases. Practicing dermatopathologists should be aware of this tumor given its low-grade appearance and histologic resemblance to other primary cutaneous adnexal and metastatic neoplasms

Gene Fusion Characterization of Rare Aggressive Prostate Cancer Variants ‐ Adenosquamous Carcinoma, Pleomorphic Giant Cell Carcinoma, and Sarcomatoid Carcinoma: An Analysis of 19 Cases

Aims We evaluated the molecular underpinnings of rare aggressive prostate cancer variants adenosquamous, pleomorphic giant cell, and sarcomatoid carcinomas. Methods and Results We retrieved 19 tumors with one or more variant(s) and performed ERG immunohistochemistry, a next‐generation sequencing assay targeting recurrent gene fusions, and fluorescence in situ hybridization (FISH) for ERG and BRAF. Divergent differentiation included: sarcomatoid (n=10), adenosquamous (n=7), and pleomorphic giant cell carcinoma (n=7). Five patients had more than one variant. Four had variants only in metastases. ERG rearrangement was detected in 9 (47%, 7 via sequencing, showing TMPRSS2‐ERG and one GRHL2‐ERG fusion, and 2 via FISH, showing rearrangement via deletion). Of these, ERG immunohistochemistry was positive in the adenocarcinoma for 8/9 (89%) but only 5/9 (56%, typically decreased) in the variant. One patient had false‐positive ERG immunohistochemistry in the sarcomatoid component despite negative FISH. Two (11%) harbored BRAF fusions (FAM131A‐BRAF and SND1‐BRAF). Conclusions ERG gene fusions are present in these rare prostate cancer variants with a close frequency to conventional prostate cancer (9/19, 47%). ERG immunohistochemistry usually detects rearrangement in the adenocarcinoma but is less sensitive for the variant histology with weak to negative staining. Adenosquamous and sarcomatoid variants particularly can occur together. Molecular assessment may be an additional tool in select cases to confirm prostatic origin of unusual tumors. The presence of 2 BRAF gene rearrangements suggests that this gene fusion may be enriched in this setting, as RAF kinase fusions have been previously reported in 1‐2% of prostate cancers

Methimazole induced cutaneous leukocytoclastic vasculitis (LCV) in Anca negative patient

A 64 y.o. Caucasian female with past medical history of hypertension, diabetes, asthma, and Graves\u27 disease with progressive dyspnea secondary to exudative large pleural effusion with a differential diagnosis of neoplastic, collagen vascular or drug induced lung disease. The patient was admitted with uncontrolled hypertension and Graves\u27 disease and started on metopro-lol, lisinopril and methimazole. One week later she developed small red macules on her forearms, hands, and ankles (Figures 1 and 2). ANA was positive but ANCA was negative. Left forearm punch biopsy showed prominent superficial perivascular neutrophilic leukocytoclasia and purpura with abundant eosinophils (Figures 3 and 4) and accompanying positive DIF findings (IgG and C3: 3+ interrupted granular staining in superficial dermal vessel walls. IgM, IgA and Fibrinogen: negative) favoring a drug associated ANCA-negative LCV. The macular rash improved after discontinuing me-thimazole. In conclusion, the association between DIF positive LCV and Methimazole with a negative ANCA is rare and should be considered in the clinical differential of drug induced palpable purpura indicating skin biopsy and DIF confirmation

Delayed Hemolytic/Serologic Transfusion Reactions (DSHTR): Correlation of Laboratory Findings with the Clinical Manifestations of Hemolysis

Background: DSHTR incidence is reported as 1 in 2,500 transfusions, presenting days to months after the transfusion. The published data addressing the correlation between the strength of the antibodies detected after a DSHTR has taken place and the corresponding clinical symptoms as measured by laboratory parameters that assess the presence of hemolysis is limited. Aims: The aim of this study is to evaluate the correlation between the results of the DAT, automated and manual antibody reactivity strength with the corresponding clinical parameters of Hemoglobin, Lactate Dehydrogenase (LDH), Bilirubin, and Haptoglobin. Methods: A DSHTR is defined as discovering a new antibody within 28 days of a transfusion. For all positive antibody screens, a work-up is initiated consisting of identification panels, DATs, antigen typing of the red cells transfused, and eluates at the discretion of the Transfusion Medicine Physician. Additional laboratory testing for hemolysis is requested when indicated. A retrospective review was conducted of patients who were identified as having a DSHTR. Levels of Hemoglobin, LDH, and Bilirubin were recorded within the 28-day period. The clinical parameters were compared against the reaction strength of the antibody reactions. The automated strength was measured by Solid phase. The manual testing consisted of a 15-min incubation using LISS and adding Monospecific IgG. The DAT was performed manually by adding Poly-specific IgG and then testing with Monospecific IgG and C3d. Results: 44 DSHTR cases/54 antibodies present Rh: 17/44 (39%) Non-Rh: 21/44 (47%) Combination: 6/44 (14%)-Rh Group: 6/17 (35%): automated strength of 3+ or 4+ 11/17 (65%): automated strength of 1+ or 2+-Non-Rh Group: 7/21 (33%): automated strength of 3+ or 4+ 14/21 (66%): automated strength of 1+ or 2+-DAT: RH Group: 10/17 (63%): negative result with clinical hemolysis 5/17 (30%): positive result with clinical hemolysis-Non-Rh Group: 13/21 (62%): negative result with clinical hemolysis 5/21 (24%): positive result with clinical hemolysis-Combination Group: 4/7 (57%): negative result with clinical hemolysis evident 3/7 (43%): positive result with clinical hemolysis evident The RH Group and non-Rh group had 11 and 10 cases performed manually, and results were 2+ or weaker further indicating the manual strength did not correlate with the clinical hemolysis. Likewise, in 31/44 (70%) the DAT was negative, and did not show any correlation with clinical hemolysis. However, when LDH and Bilirubin were measured, the two parameters increased as the automated strength of the antibodies increased. Summary/Conclusions: Most of the DSHTR investigation was not associated with overt accelerated red cell destruction. A strong correlation was observed only between the automated immunohematology testing results and other laboratory markers of hemolysis. In our experience, the direct antiglobulin test and manual strength showed no correlation

The Role of Therapeutic Plasma Exchange for the Treatment of Allograft Rejection in Solid Organ Transplant: A Single Center Experience

Background: Transplanted organ failure due to antibody mediated rejection in ABO-compatible organs is a serious complication with a bad prognosis. The goal treatment in these cases encompasses the following strategies: adjustment of the immunosuppressive medications, IVIG infusion, antibody removal by therapeutic plasma exchange, and/or the use of target-specific monoclonal antibody medications to lymphocytes, plasma cells, and/or complement. The 2016 American Society for Apheresis has assigned a category I to the use of therapeutic plasma exchange for the treatment of ABO-compatible antibody mediated rejection in kidney, but a category III to all other ABO compatible organs: Liver, Lung, and Heart. At our institution, a standardized approach for the use of therapeutic plasma exchange as a supportive intervention for ABO-compatible immune mediated rejection, regardless of the organ type, has been in place since 2011. Aims: A retrospective review was performed to evaluate our patient outcomes using therapeutic plasma exchange for the treatment of antibody mediated allograft rejection in ABO-compatible solid organ transplantation. Methods: Patients used for the retrospective review were selected from an existing therapeutic apheresis list. The therapeutic plasma exchange protocol consists of: adjustment of the immunosuppressive medications, IVIG infusion, antibody removal by therapeutic plasma exchange, and/or the use of target-specific monoclonal antibody medications to lymphocytes, plasma cells, and/or complement. It is performed as follows: One plasma volume exchange is performed on days 1,2,3, 5, 7, 9 along with one or more of the above strategies followed by an IVIG infusion. Cases with allograft rejection in which plasmapheresis was not used were excluded. Results: We evaluated the effectiveness of therapeutic plasma exchange in 37 patients who experienced allograft rejection in solid organ transplant between 2013-2016. Eight transplanted patients (heart, lung) had more than one set for separate rejection episodes and all liver transplant recipients received photo-pheresis after the therapeutic plasma exchange. • Total number of patients: 36 o Heart: 11 o Lung: 22 o Liver: 3 • Rejection Types: o Antibody-Mediated: 6 o Cellular/Antibody-Mediated: 28 o Uncertain: 2 All patients had IVIG as an adjunct, and only six patients received Rituximab, Eculi-zumab or Bortezomib. All procedures were tolerated well. There were two adverse events reported in association with the therapeutic plasma exchange: 1 transient febrile episode and 1 citrate toxicity, without sequelae. Patient Survival: • Heart: 63.6% o Alive: 7 o Deceased due to organ rejection: 2-18% o Deceased due to disease not related to rejection: 2-18% • Lung: 50% o Alive: 11 o Deceased due to organ rejection: 5-23% o Deceased due to disease not related to rejection: 6-27% • Liver: 100% o Alive: 3 21/36 patients (59%) are alive, 7/36 patients (19%) are deceased due to organ rejection, and 8/36 patients (22%) are deceased due to disease not related to rejection. Summary/Conclusions: The use of therapeutic plasma exchange for the treatment of antibody mediated rejection in solid organ transplant is safe and effective when used along with other treatment modalities. Further studies will help determine whether it can be reproduced in larger cohorts and whether it is more effective in certain organs

Trichostasis Spinulosa of the Heel: Unique Presentation with Characteristic Morphology

Trichostasis Spinulosa is a peculiar lesion of the hair follicle that typically presents on the face. We present a case of a 59 years old Middle Eastern male who presented with a dark lesion on his heel. Examination revealed a 1.7 cm well-circumscribed black necrotic plaque with surrounding overhanging border with a differential diagnosis of melanoma. Histologically, the lesion was formed by inflamed clusters of numerous small hair shafts, consistent with Trichostasis Spinulosa of the heel. We report this case because of its unusual location and unique presentation

Primary Pleural Extranodal Marginal Zone Lymphoma Presenting as Bilateral Chylothorax

Here we describe a case of pleural extranodal marginal zone lymphoma presenting as bilateral chylothorax which has not been reported in the literature prior to this. Primary pleural lymphomas are a rare entity most commonly associated with chronic infections, autoimmune conditions or long-standing pyothorax which were not seen in this case. Chylous pleural effusions in this patient were successfully managed with chemotherapy for the underlying lymphoma