PRAME Immunohistochemical Expression and TERT Promoter Mutational Analysis as Ancillary Diagnostic Tools for Differentiating Proliferative Nodules From Melanoma Arising in Congenital Nevi.

ABSTRACT: Proliferative nodules (PNs) are benign melanocytic proliferations that typically develop within congenital melanocytic nevi. These tumors have overlapping histological features with melanoma. Ancillary immunohistochemistry and genomic sequencing are often used in diagnostically challenging cases. To assess the utility of preferentially expressed antigen in melanoma (PRAME) immunoreactivity and telomerase reverse transcriptase (TERT) promoter mutation analysis in distinguishing PNs from melanoma arising in congenital nevi cases. Twenty-one PNs and 2 melanomas arising in congenital nevi were immunohistochemically stained with PRAME. Cases with adequate tissue were also assessed for TERT promoter mutations through sequencing studies. The positivity rates in the PN cases were compared with those of the melanomas. Two of 21 PN cases were diffusely positive for PRAME (≥75% of the tumor cells positive). Two of 2 melanomas arising in congenital nevus cases were also diffusely PRAME positive. The difference was statistically significant using a Fisher exact test. None of the tumors harbored TERT promoter mutations. PRAME immunohistochemical marker may have diagnostic value in distinguishing diagnostically challenging PNs from melanoma, but diffuse expression is not specific for melanoma.

TERT Promoter Mutational Analysis as an Ancillary Diagnostic Tool for Diagnostically Challenging Melanocytic Neoplasms.

ABSTRACT: Telomerase reverse transcriptase promoter mutations (TPMs) have been shown to be common in melanoma and uncommon in benign nevi. To assess the use of TPMs as an ancillary diagnostic tool, we report the concordance of the TPM status with the final diagnosis in clinical cases with distinct differential diagnostic scenarios: dysplastic nevus versus melanoma, atypical Spitz nevus versus melanoma, atypical deep penetrating nevus (DPN) versus melanoma, and atypical blue nevus versus malignant blue nevus. In a control cohort, we found a positive TPM in 51/70 (73%) of the total melanomas with the highest frequency in vertical growth phase melanoma cases. Conversely, only 2/35 (6%) dysplastic nevi in our control cases were TPM-positive and b were severely atypical dysplastic nevi. Our clinical cohort of 257 cases had a positive TPM in 24% of cases diagnosed as melanoma and in 1% of cases with a benign diagnosis. The overall concordance of the TPM status with the final diagnosis was 86%. The TPM status had the greatest concordance (95%) with the final diagnosis in the atypical DPN versus melanoma group, with the rest of the groups ranging between 50% and 88%. Overall, our results suggest that TPMs are most useful in the differential diagnosis of atypical DPN versus melanoma. It also has some value in the differential diagnosis of atypical Spitz tumor versus melanoma and dysplastic nevus versus melanoma, whereas in our cohort, it did not contribute meaningfully to differentiating malignant blue nevus and atypical blue nevus.

Treatment of traumatic hypertrophic scars and keloids: a systematic review of randomized control trials.

Exaggerated healing and remodeling after skin injury may cause hypertrophic and keloidal scars, which are associated with functional and quality of life impairment. There is limited guidance available regarding the relative effectiveness of therapies for hypertrophic scars and keloids. In this review, we aim to compare the effectiveness of treatments for hypertrophic scars and keloids. MEDLINE, Embase, Scopus, and the Cochrane Collaboration database were searched from inception to March 2019 for randomized control trials of treatments for hypertrophic and keloid scars that included 20 or more patients. Outcomes evaluated included the standardized mean reduction in scarring and adverse events. The type of scar and the demographic features were analyzed for their effect on clinical outcome. Based on 25 included clinical trials, intralesional injection (64.1% [95% CI 60.8-67.5%]) may be more effective than physical (29.9% [95% CI 28.9-30.9%]) or topical treatments (34% [95% CI 31.8-36.8%]). Combination of 5-fluorouracil and triamcinolone (9:1 dilution) appeared superior among intralesional treatments for keloids. Ablative laser and pulsed-dye laser were the most useful laser treatments. Regression modeling showed laser treatment response was linked to Fitzpatrick skin type (p = 0.002). Adverse events were uncommon for all treatments and mostly transient. Intralesional treatments for keloid and hypertrophic scars may be the most reliable treatment option to improve pathologic scars, while laser treatment may have specific benefits for Fitzpatrick skin types I-III over types IV-VI. Management of pathological scars is an area of critical need, where appropriate treatment can have a significant impact on quality of life.

Highlighting the Diversity of Desmoplastic Small Round Cell Tumor: A Case Series.

Desmoplastic small round cell tumor (DSRCT) is a rare malignant tumor that occurs mainly in the retroperitoneum of children and young adults. In its prototypical form, DSCRT displays characteristic morphology with nested primitive small round cells in a desmoplastic stroma and a distinctive immunophenotype with polyphenotypic differentiation. However, DSCRT can also exhibit a broader clinical, histologic and immunohistochemical spectrum and, therefore, cause diagnostic difficulties. Given that DSCRT is an aggressive and nearly universally fatal disease, making the correct diagnosis is critically important. Herein, we report three patients with DSRCT and unusual clinical, morphologic or immunohistochemical characteristics, in order to highlight its remarkable diversity and increase awareness of this unusual, distinctive neoplasm.

Interdisciplinary Quality Improvement Led by the Molecular Pathology Laboratory Expedites Diagnosis of Acute Promyelocytic Leukemia.

OBJECTIVES: Acute promyelocytic leukemia (APL) requires emergent treatment while definitive laboratory results are pending. Following the death of a patient whose diagnosis was delayed, we sought to improve our institution's workflow by using the EPIDEM (Exploration, Promotion, Implementation, Documentation, Evaluation, Modification) quality improvement model. METHODS: APL is confirmed by identifying translocation t(15;17)(q24;q21) PML-RARA by using either molecular or cytogenetic methods on peripheral blood or bone marrow specimens. We used the EPIDEM model to decrease the turnaround time (TAT) of molecular diagnosis by improving communication and developing reflex testing. We additionally compared 32 APL cases against a control group of 18 suspected APL cases. RESULTS: Our review of 687 multiplex polymerase chain reaction orders and 33 PML-RARA orders (January 2012 to April 2021) showed an initial TAT decrease from 4.48 days to 2.71 days (P < .0001), which further decreased to 0.64 days (P < .0001) after implementation of the PML-RARA qualitative assay. Compared with patients suspected of having APL, patients with confirmed APL had higher dimerized plasmin fragment D (P = .0145), lower fibrinogen (P ≤ .0001), and lower WBC (P ≤ .0001). CONCLUSIONS: By using the EPIDEM model, with its emphasis on local context, culture, and resources, improved communication and workflow changes enabled us to reduce the time needed to diagnose APL to 0.64 days and identify potential locally derived screening cutoffs.

Benign and Intermediate-grade Melanocytic Tumors With BRAF Mutations and Spitzoid Morphology: A Subset of Melanocytic Neoplasms Distinct From Melanoma.

The current classification of Spitz neoplasms in the World Health Organization (WHO), Fourth Edition defines Spitz neoplasms as melanocytic proliferations with characteristic Spitz morphology and a Spitz-associated genomic fusion or HRAS mutation. In contrast, melanocytic neoplasms with BRAF mutations are considered typical of common acquired nevi, dysplastic nevi, and melanomas from intermittent sun-damaged skin. However, increased utilization of ancillary testing methods such as BRAFV600E immunohistochemistry and sequencing studies have made apparent a subgroup of benign-grade and intermediate-grade melanocytic neoplasms with Spitzoid morphology that harbor BRAFV600E mutations. We refer to these cases as BRAF mutated and morphologically Spitzoid (BAMS) nevi and tumors. Two experienced dermatopathologists reviewed a series of 36 BAMS nevi/tumors. Cases in which a diagnosis of melanoma was favored were excluded. The histomorphologic, clinical, and molecular findings were assessed by immunohistochemistry, fluorescence in situ hybridization, and next-generation sequencing using validated gene panels. Characteristics of BAMS nevi/tumors were compared with a control set of Spitz tumors with previously reported fusion proteins. BAMS nevi/tumors had a decreased proportion of Kamino bodies (P=0.03) and a higher proportion of cytoplasmic pigmentation (P<0.00001). There were no differences in other morphologic features such as the silhouette, epidermal hyperplasia, pagetosis, and cytologic atypia compared with fusion-induced Spitz tumors. In 6/17 cases where next-generation sequencing studies were available, recurrent mutations in the KMT gene family were seen. This was higher than the proportion of such mutations seen in fusion Spitz tumors and lower than the frequency in cutaneous melanoma.

Histiocytic sarcoma arising from a lymph node: a diagnostic conundrum.

Histiocytic Sarcoma (HS) is extremely rare, with only a few hundred cases reported in the literature. The majority of patients present with symptoms due to unifocal or multifocal extra-nodal disease. Less than 20% of these cases show solitary involvement of a lymph node. We report a case of a solitary HS in a 53-year-old woman presenting with a 2.7-cm right groin mass arising from an inguinal lymph node. The initial cytologic examination of the tissue showed a high-grade spindle-shaped morphology with high-grade mitotic activity. A high-grade sarcoma was initially considered considering the absence of normal lymphoid aggregate and the presence of high-grade cytologic features in the cells. To evaluate the tumor in its entirety, the mass was surgically excised. A histological examination of the tumor showed focal rimming of the lymphoid tissue at the periphery and a centrally located stellate necrotic focus. The tumor cells had an epithelioid to spindle cell morphology along with large uniform nuclei and prominent nucleoli. A high mitotic index was present. Immunohistochemistry (IHC) stains showed strong positivity for CD68, CD163, and Vimentin, and were weakly positive for SMA and CD45. Based on the histologic and clinical examination, a diagnosis of HS was made. Multiple malignancies can mimic HS histopathology and the rarity of this tumor makes the diagnosis more challenging. No fine-needle aspiration (FNA) criteria for its diagnosis have been recognized. Herein, we report a rare case of an isolated HS involving a lymph node which resembled high-grade sarcoma on the FNA biopsy to raise awareness among our surgical pathologist colleagues.

Pigmented Epithelioid Melanocytoma: Morphology and Molecular Drivers.

Pigmented epithelioid melanocytoma (PEM) was originally described based on keen morphologic analysis identifying a group of melanocytic tumors sharing heavily pigmented epithelioid melanocytes. It is defined as heavily pigmented epithelioid, spindled, and dendritic melanocytes with characteristic vesicular nuclei, prominent nucleoli, and melanophages. PEM often involves regional lymph nodes. Recent advances in molecular analysis have allowed for subclassification of PEM into more specific subsets of melanocytic tumors. The most common subsets include PRKCA fusions, which result in pure PEMs with sheets of monomorphic epithelioid melanocytes, and PEMs with combined pattern and mutations in both PRKAR1A and BRAF.

Burkitt-Like Lymphoma with 11q Aberration: A Case Report and Review of a Rare Entity.

Burkitt-like lymphoma with 11q aberration is a rare diagnostic entity commonly occurring in children and young adults with a nodal presentation. This entity shares many similar morphologic and immunophenotypic features with conventional Burkitt lymphoma and other aggressive B-cell lymphomas, making its recognition challenging. However, the presence of its characteristic 11q gain/loss pattern is helpful in the diagnosis. We report a case of Burkitt-like lymphoma presenting as a right neck mass in a 17-year-old female patient that demonstrated no improvement with antibiotic therapy. The neoplasm displayed a diffuse proliferation of intermediate-sized atypical lymphoid cells with prominent nucleoli in a background of apoptotic debris, morphologically raising concern for conventional Burkitt lymphoma. Subsequent immunohistochemical and cytogenetic studies established the most likely diagnosis of Burkitt-like lymphoma with 11q aberration. Though rare, Burkitt-like lymphoma exhibits significant morphologic overlap with other high-grade B-cell lymphomas, making it an important entity to consider on the differential diagnosis of these lesions.

Subcutaneous desmoplastic small round-cell tumor: An unusual primary location expanding the differential of superficial round-cell tumors.

Desmoplastic small round-cell tumor (DSRCT) is a rare, aggressive malignant tumor, which in the great majority of cases arises at abdominal-pelvic sites. Nevertheless, rare cases of primary extra-abdominal tumors have been reported. In challenging cases, its molecular hallmark, the EWSR1-WT1 reciprocal translocation, can be exploited diagnostically by various molecular techniques. Herein, we report an extremely rare case of primary subcutaneous DSRCT in an effort to raise awareness among our dermatopathology colleagues by expanding the differential of superficial round-cell tumors.