Individualized Surgery: Gamma-Probe-Guided Lymphadenectomy in Patients with Clinically Enlarged Lymph Node Metastases from Melanomas

BACKGROUND: The value of a preoperative lymphoscintigraphy in melanoma patients with clinically evident regional lymph node metastases has not been studied. Therapeutic lymph node dissection (TLND) is regarded as the clinical standard, but the appropriate extent of TLND is controversial in all lymphatic basins. PATIENTS AND METHODS: Of the 115 consecutive patients with surgery on palpable lymph node metastases, 34 received a pre-operative lymphoscintigraphy. Lymphatic drainage to a second nodal basin outside the clinically involved basin was found in 15 cases. In 13 patients, the ectopic tumor-draining lymph nodes were excised as in a sentinel node biopsy. The lymph nodes from the TLND specimens were postoperatively separated and classified as either radioactive or non-radioactive. RESULTS: A total of 493 lymph nodes were examined pathologically. The largest macrometastasis maintained the ability to take up radiotracer in 77% of cases. Radioactively labeled lymph nodes carried a higher risk of being involved with metastasis. The proportions of tumor involvement for radioactive and non-radioactive lymph nodes were 44.5 and 16.9%, respectively (P=0.00002). Of the 13 ectopic nodal basins surgically explored, six harbored clinically occult metastases. CONCLUSION: In patients undergoing TLND for palpable metastases, tumor-draining lymph nodes in a second, ectopic nodal basin should be excised, because they could be affected by occult metastasis. With respect to radioactive lymph nodes situated within the nodal basin of the macrometastasis but beyond the borders of a less-radical lymphadenectomy, further studies are needed

Correction. "The 5th edition of The World Health Organization Classification of Haematolymphoid Tumours: Lymphoid Neoplasms" Leukemia. 2022 Jul;36(7):1720-1748

We herein present an overview of the upcoming 5th edition of the World Health Organization Classification of Haematolymphoid Tumours focussing on lymphoid neoplasms. Myeloid and histiocytic neoplasms will be presented in a separate accompanying article. Besides listing the entities of the classification, we highlight and explain changes from the revised 4th edition. These include reorganization of entities by a hierarchical system as is adopted throughout the 5th edition of the WHO classification of tumours of all organ systems, modification of nomenclature for some entities, revision of diagnostic criteria or subtypes, deletion of certain entities, and introduction of new entities, as well as inclusion of tumour-like lesions, mesenchymal lesions specific to lymph node and spleen, and germline predisposition syndromes associated with the lymphoid neoplasms

Pathologic Diagnosis of Cutaneous Lymphomas.

Primary cutaneous lymphomas comprise a prognostically heterogeneous group of lymphocytic skin neoplasms, which display a broad spectrum of clinical, histologic, immunophenotypic, and genetic features. The histopathological examination plays an essential role and is often the starting point in the diagnostic workup of cutaneous lymphomas. In most cases, the histopathological and the phenotypic analysis alone are limited to provide a list of differential diagnoses. As a consequence of overlapping clinical, histologic, phenotypic, and genetic features among several entities of cutaneous lymphomas, the clinicopathological correlation is of utmost importance to achieve the final diagnosis

Cutaneous lymphomas: an update. Part 2: B-cell lymphomas and related conditions

Primary cutaneous B-cell lymphomas (PCBCL) are the second most common form of primary cutaneous lymphomas and account for approximately 25%-30% of all primary cutaneous lymphomas. Both forms of low-grade malignant PCBCL, primary cutaneous follicle center lymphoma (PCFCL) and primary cutaneous marginal zone lymphoma of mucosa-associated lymphoid tissue-type (MALT lymphoma) (PCMZL) represent the vast majority of PCBCL and show an indolent slowly progressive course and an excellent prognosis despite a high recurrence rate. Genetic analysis indicates that PCMZL differ from other forms of extranodal MALT lymphomas. The more common class-switched and the non-class-switched form of PCMZL can be distinguished as two distinctive subsets that differ in the cellular composition, IgM expression, and biological behavior with extracutaneous involvement found in the non-class-switched form. Recently, unusual clinical and histological forms of PCMZL and PCFCL manifesting with miliary or agminated lesions have been described that are diagnostically challenging. In contrast to PCMZL and PCFCL, primary cutaneous diffuse large B-cell lymphoma, leg type, and other rare forms of large B-cell lymphomas such as intravascular large B-cell lymphoma have an unfavorable prognosis. There is an emerging group of Epstein-Barr virus (EBV)-driven B-cell lymphoproliferations including posttransplant lymphoproliferative disorders and mucocutaneous ulcer occurring in immunocompromised patients and EBV-associated diffuse large B-cell lymphoma of the elderly arising in the setting of senescence-linked immunodeficiency. This review reports on recent findings expanding the spectrum of clinicopathological features, differential diagnostic aspects, and the pathogenesis of PCBCL and discusses the group of EBV-associated B-cell lymphoproliferations involving the skin

Stage‐related PD‐L1 expression in Kaposi sarcoma tumor microenvironment

Background The immune checkpoint molecule PD‐L1 represents an important target in oncological immune therapy. The aim of our study was to evaluate PD‐L1 expression and the composition of the tumor microenvironment (TME) in Kaposi sarcoma. Methods Immunohistochemical stains were performed for PD‐L1, CD3, CD33, CD68, and CD168 in 24 Kaposi sarcoma samples. In PD‐L1‐positive cases, the double stains for PD‐L1, CD31, podoplanin, and HHV8 were added. Results PD‐L1 was observed in 71% of the samples and was predominantly located in the TME. PD‐L1 expression was significantly higher in nodular stage than in patch/plaque stage. The TME consisted of CD68+/CD163+ macrophages, CD33+ myloid‐derived suppressor cells and monocytes and CD3+ T‐cells. The TME showed a peritumoral distribution in nodular stage, in contrast to a diffuse distribution in patch/plaque stage. In 12 samples (50%), no plasma cells were found. Conclusion In nodular stage of KS, the TME is pushed back in the periphery of the tumor nodules. The PD‐L1‐positive TME between the tumor cells might protect them from the immune attack. An anti‐PD‐L1 treatment might be promising in KS patients

Galectin-3 expression in primary cutaneous CD30-positive lymphoproliferative disorders and transformed mycosis fungoides

BACKGROUND: In nodal anaplastic large cell lymphoma, strong expression of galectin-3 (Gal-3) has been found, but only very few cases of primary cutaneous lymphoma have so far been examined. OBJECTIVES: To investigate 11 primary cutaneous anaplastic large cell lymphomas (PCALCL), 47 lymphomatoid papuloses (LYP) and 14 cases of transformed mycosis fungoides with CD30 expression (MF-T) for Gal-3 expression. METHODS: A Gal-3 score was applied using a photo-based morphometric evaluation program. Double staining for CD30 and Gal-3 was performed. Furthermore, we recorded the cellular and extracellular sublocalization of the signal. RESULTS: The Gal-3 expression in CD30+ tumor cells was significantly lower in MF-T in contrast to CD30+ lymphoproliferative disorders (CD30 LPD; p < 0.001), but we found no differences between PCALCL and LYP (p = 0.42). In PCALCL Gal-3 was more often localized in the cytoplasm in contrast to LYP, in which an equal distribution in the cytoplasm and the nucleus was more common (p = 0.9). CONCLUSIONS: The lower Gal-3 expression in MF-T in comparison to CD30 LPD might be an additional criterion to differentiate both entities. The different sublocalization of the Gal-3 signal might reflect a different biological function and behavior

Detection of Merkel cell polyomavirus and human papillomaviruses in merkel cell carcinoma combined with squamous cell carcinoma in immunocompetent European patients

BACKGROUND: About 10% of patients with Merkel cell carcinoma (MCC) suffer from an associated squamous cell carcinoma (SCC). In European patients, Merkel cell polyomavirus (MCPyV) is detectable in 60%-88% of the MCC tumors. In combined lesions, MCPyV was not detectable so far. METHODS: We investigated 2 combined tumors of MCC and SCC for the presence of MCPyV and human papillomavirus (HPV) by polymerase chain reaction and immunohistochemistry. RESULTS: In both lesions, MCPyV DNA was found, and in 1 case, HPV DNA was also detected. This is the first report of a coinfection with HPV and MCPyV in combined MCC-SCC tumors. CONCLUSIONS: The results underline the hypothesis of co-cancerogenesis of 2 oncogenic viruses in nonmelanoma skin cancer. Technical reasons and a low viral copy number of MCPyV hampering immunohistochemical detection may be responsible for the negative results in the literature

Are there distinct clinical and pathological features distinguishing Idiopathic from Drug-Induced Subacute Cutaneous Lupus Erythematosus? A European retrospective multicenter study

BACKGROUND: Clinical and pathological criteria to distinguish drug-induced subacute lupus erythematosus (DI-SCLE) from idiopathic (I-SCLE) are controversial. OBJECTIVE: Aim of the survey was a retrospective analysis of a consistent number of iatrogenous and idiopathic SCLE cases, by means of clinical and histopathological investigation. METHODS: Eleven European University Dermatology Units collected all diagnosed cases from January 2000 to December 2016. Board certified dermatopathologists reviewed the histopathologic specimens. Statistical analysis included Student's t-test, exact test of goodness-of-fit, Fisher's test, Cochran-Mantel-Haenszel for repeated measures. RESULTS: Out of 232 patients, 67 (29%) belonged to the DI-SCLE group. Patients with DI-SCLE were significantly older and complained more systemic symptoms than those with I-SCLE. No statistical differences were found for presentation pattern or serology, while histopathology showed for I-SCLE a significant association of mucin deposition (p=0, 000083) and direct immunofluorescence positivity for granular IgM, C3 deposits on the basement membrane zone (p=0, 0041), and of leukocytoclastic vasculitis (p=0, 0018) for DI-SCLE. LIMITATIONS: This is a retrospective study. CONCLUSION: An integrated clinical and immunopathological evaluation is useful to differentiate I-SCLE from DI-SCLE. Older age at onset and more frequent systemic symptoms characterize DI-SCLE. Mucin deposition and immunofluorescence findings are found in I-SCLE, while leukocytoclastic vasculitis in DI-SCLE