Comparison of two immunohistochemical staining protocols for ALK demonstrates non-inferiority of a 5A4 clone-based protocol versus an ALK01 clone-based protocol for the diagnosis of ALK + anaplastic large cell lymphoma.

Detection of ALK rearrangement and/or expression of the ALK protein is an essential component in the evaluation of many neoplasms. Variability has been reported in the ability of different antibody clones to detect ALK expression. The ALK01 clone is commonly used to detect ALK expression in ALK-positive anaplastic large cell lymphoma (ALK + ALCL). However, this clone has been shown to lack sensitivity when used for solid tumors. The aim of this study was to determine if our high-sensitivity 5A4-based immunohistochemistry protocol is non-inferior to our ALK01-based protocol for the detection of ALK expression in ALK + ALCL. To compare the two protocols, we stained tissue microarrays of 126 hematolymphoid neoplasms and an additional 21 primary cutaneous ALK-negative anaplastic large cell lymphomas with both protocols. All 28 ALK + ALCL samples that were positive for the ALK01 antibody were also positive for the 5A4 clone. Three cases on the tissue microarray that were negative with the ALK01 antibody were clearly positive with the 5A4 antibody. We subsequently stained whole tissue sections of these three cases with the ALK01 antibody and found that these three cases were indeed positive with the ALK01 protocol, suggesting that the absence of staining on the tissue microarray samples was due to a combination of sampling error as well as a dimmer signal with the ALK01 protocol. Our study demonstrates that our 5A4-based protocol is non-inferior to the ALK01 antibody for the diagnosis of ALK-positive anaplastic large cell lymphoma, thus allowing our laboratory to discontinue the use of the ALK01-based protocol.

A case of giant anastomosing hemangioma of the kidney with extramedullary hematopoiesis: A great mimicker.

Anastomosing hemangioma (AH) are rare mesenchymal neoplasms affecting kidney with about 50 cases reported in English literature. In general, they are accidentally detected during examination or imaging done for nonspecific symptoms or wellness check-up. There are no key diagnostic features on the imaging modalities. The most common preoperative diagnosis has been a malignant primary renal carcinoma. Surgical resection remains the mainstay of treatment and of choice in symptomatic lesions. We are presenting a rare case of giant AH of the kidney mimicking a renal cell carcinoma on imaging. The lesions are characterized by anastomosing sinusoidal-like vascular spaces lined by banal endothelial cells with occasional hobnail morphology and associated with extramedullary hematopoiesis. The treatment of choice could be a conservative approach in small and asymptomatic lesions and patients with pre-existing renal dysfunction; hence, this entity should be in the differential of vascular renal neoplasms considering its proclivity to the urogenital tract. This is the first case in Indian literature to the best of our knowledge.

Myeloid Cell Nuclear Differentiation Antigen (MNDA) Positivity in Primary Follicles: Potential Pitfall in the Differential Diagnosis With Marginal Zone Lymphoma.

Myeloid cell nuclear differentiation antigen (MNDA) is an immunohistochemical marker that is used to distinguish marginal zone lymphomas (MZLs) from other small B-cell lymphomas. An index case that showed MNDA staining in primary follicles prompted the current study to evaluate whether MNDA expression is widespread in primary follicles and to address whether it poses a potential diagnostic pitfall. Of the 15 cases with primary follicles identified by a search of the laboratory information system, 7 had positive MNDA staining. In all cases, there was weak nuclear staining similar to what is typical of MNDA staining in MZLs. All cases showed intense nuclear signal in myeloid lineage cells such as neutrophils, which served as positive internal controls. The histologic and cytologic features of primary follicles and MZLs showed overlapping features, particularly in small biopsies. Our results indicate that weak nuclear MNDA staining can act as a potential pitfall in the evaluation of small B-cell lymphomas. Correlation with other immunohistochemical markers that are useful in the workup of small B-cell lymphomas, as well as those that outline immunoarchitectural features of lymphoid follicles, is suggested when both entities are part of the differential diagnosis. Our results underscore the need for caution in the interpretation of weak nuclear MNDA staining in the evaluation of small B-cell lymphomas.

Genetic Subtypes of Systemic Anaplastic Large Cell Lymphoma Show Distinct Differences in PD-L1 Expression and Regulatory and Cytotoxic T Cells in the Tumor Microenvironment.

Anaplastic large cell lymphomas (ALCL) encompass several subgroups that differ in their clinical presentation, genetic features, and prognosis. We characterized the genetic subgroups of 74 patients with ALCL and correlated programmed death ligand 1 (PD-L1) protein expression and compared the densities and ratios of FOXP3+ T regulatory cells and CD8+ tumor-infiltrating lymphocytes (TILs) in tumor cells and the immune microenvironment. The subgroups included anaplastic lymphoma kinase (ALK)-positive (ALK+) ALCL and ALK-negative (ALK-) ALCL and DUSP22-rearranged and nonrearranged ALK- ALCL. None of our cases represented the TP63-rearrangement ALK- ALCL subgroup. Our results showed that ALK+ ALCL had a higher expression of PD-L1 in the tumor cells, in contrast to ALK- ALCL, which expressed high PD-L1 in tumor-associated macrophages (TAMs). DUSP22-rearranged ALK- ALCL lacked PD-L1 expression in the tumor cells and instead expressed PD-L1 only in TAMs. There was a significant positive correlation of PD-L1 expression between tumor and TAMs in ALK+ ALCL with a negative correlation in ALK- ALCL. Systemic ALCL subgroups had similar densities of CD8+ tumor-infiltrating lymphocytes and FOXP3 T regulatory cells, but differences were observed in the ratio of CD8/FOXP3. Our results suggest that alterations in tumor microenvironment and immune responses exist among systemic ALCL subgroups and these features may account for different clinical behavior and prognosis.

Clinicopathological Profile and Outcomes of Follicular Dendritic Cell Sarcoma of the Head and Neck Region - A Study of 10 Cases with Literature Review.

INTRODUCTION: Follicular Dendritic Cell Sarcomas (FDCS) are rare disorders of the lymph node and soft tissues. Accurate characterization of these neoplasms is important in planning optimal treatment given its potential for recurrence and metastasis. AIM: To analyse the clinicopathological profile and outcomes of a series of 10 cases of follicular dendritic cell sarcoma arising in the head and neck region diagnosed at our regional cancer centre. MATERIALS AND METHODS: A series of 10 cases of FDCS of the head and neck region from the hospital registry of head and neck cancers diagnosed between 2007 and 2013 were collected and analysed retrospectively. Clinical details, pathologic features, immuno-phenotypic profile, treatment approach and outcomes over a period of 5 years were noted. The Recurrence Free Survivals (RFS) of all the patients were recorded. RESULTS: The median age of the patients was 57 years and the mean age was 50.9 years. Male: female ratio was 7:3. In eight of the 10 patients, the tumours were located in the tonsils. All the tumour cells showed diffuse cytoplasmic CD21 and CD23 positivity by IHC. All the 10 cases underwent surgical excision of the tumour and three cases underwent additional neck dissection for cervical lymph node enlargement. All the patients with high grade tumours were uniformly managed with Tri-modality treatment (Surgery followed by radiotherapy and chemotherapy). The overall recurrence rate was 70%. The mean and median recurrence free survival was 39.6 and 44 months, respectively. Two of the three patients who remained recurrence free at the end of the 60 months had low grade tumours. CONCLUSION: Early recognition of follicular dendritic cell sarcomas requires a high index of suspicion and bi-modality or tri-modality treatment may cure a subset of low and high grade tumours respectively and prolong recurrence in a large subset of patients. Surgery is the mainstay and the definitive modality of treatment; the advantages and benefit of adjuvant radiotherapy and chemotherapy are yet to be established. Tri-modality management may have a role in high grade patients which needs to be substantiated in future studies.

Isolated intramedullary spinal cord cysticercosis.

We report a case of intradural, intramedullary, spinal cord neurocysticercosis at dorsal 10-11 (D10-11) level in a mentally retarded male. A 38-year-old, mentally retarded male presented with weakness and stiffness in both the lower limbs and waist since one year. Magnetic resonance imaging revealed a D10-D11 intradural space occupying lesion with cord compression. Intraoperatively, the tumor was grayish white, soft, cystic, and intramedullary with a well-defined plane with surrounding cord tissue. Gross examination revealed a cystic lesion of 1.5×1×0.8 cm, with a whitish nodule of 0.3 cm in diameter. The cyst wall was thin, shiny, and translucent. Microscopic examination revealed cysticercous cyst. Spinal neurocysticercosis should be considered in differential diagnosis of spinal mass lesion in patients residing in endemic area such as India.