PD-1 blockade induces remissions in relapsed classical Hodgkin lymphoma following allogeneic hematopoietic stem cell transplantation.

BACKGROUND: Allogeneic hematopoietic stem cell transplantation and checkpoint blockade therapy are immune-based therapies that have activity in selected refractory hematologic malignancies. Interest has developed in combining these treatments for high-risk hematologic diseases. However, there is concern that checkpoint blockade could augment graft-versus-host disease, and very few studies have evaluated the safety of checkpoint blockade in the post-allogeneic setting. Here, we report the outcomes of three patients with relapsed classical Hodgkin's lymphoma following allogeneic transplant that were treated with the anti-PD-1 antibody, nivolumab. CASE PRESENTATIONS: Three patients with Hodgkin's lymphoma relapsed following allogeneic transplant received nivolumab therapy at our institution. All patients were free of graft-versus-host disease and were off of all systemic immunosuppressive medications at the time of nivolumab treatment. Nivolumab was well-tolerated in two of the patients. However, nivolumab had to be discontinued in one patient due to development of immune-related polyarthritis requiring treatment with systemic corticosteroids and methotrexate. Objective responses were observed in all three patients. CONCLUSIONS: Our case series demonstrates that anti-PD-1 therapy with nivolumab can be highly effective following allogeneic transplant for Hodgkin's lymphoma, but serious immune-related adverse events can occur, requiring very close monitoring and interruption of therapy.

Fine needle aspiration cytology of cystic primary adult granulosa cell tumor of the ovary: Potential diagnostic pitfalls with other cystic ovarian lesions.

INTRODUCTION: Fine needle aspiration(FNA) of cystic adult granulosa cell tumors(CAGCT) has been sporadically reported in the literature. We undertook a retrospective study to further elucidate the cytologic features on FNA material in order to avoid possible misinterpretation with other primary tumors of ovary. MATERIALS AND METHODS: During 1992 and 2014, FNA of five cases of CAGCT were recorded. RESULTS: The patient's age ranged from 28 to 62 years. One was bilateral and all cases involved right side of ovary. The size of tumor was 5.5 to 10 cm. FNA of the five CAGCT show similar cytologic features except one case. Four cases contained a background composed of histiocytic cells and debris material. The tumor cells were small with round to oval nuclei and fine chromatin pattern, inconspicuous nucleoli, scanty cytoplasm with rare intranuclear longitudinal grooves. Tumor cells were arranged in small groups as well as single cells were appreciated some of which were deprived of cytoplasm. Microfollicular or rosette pattern were vague, some of which contain amorphous material resembling Call-Exner bodies. In addition, two cases also showed prominent papillary component and one of which was misdiagnosed for serous papillary carcinoma. All five cases were surgically resected and CAGCT was confirmed. CONCLUSIONS: FNA of CAGCT of ovary can be a challenging diagnosis as classic cytologic features may not be present and can be confused with benign follicular cyst especially when the ultrasound study favor benign cystic lesion. Rarely this tumor may show prominent papillary component and can be confused for a more clinically aggressive tumor such as papillary serous carcinoma. Diagn. Cytopathol. 2016;44:461-465. © 2016 Wiley Periodicals, Inc.

Prognostic Value of Coexisting Lobular Carcinoma In Situ With Invasive Lobular Carcinoma.

AIMS AND OBJECTIVES: Recent studies show that lobular carcinoma in situ (LCIS) and invasive lobular carcinoma (ILC) share similar genetic molecular biology. There are increasing concerns regarding the biological significance of LCIS. The aim of this study is to investigate whether the presence of coexisting LCIS in ILC affects tumor biology and behavior and to correlate it with other clinicopathologic parameters. MATERIALS AND METHODS: In this study, 254 cases of ILC were included. Clinicopathologic parameters and immunohistochemical stains for estrogen receptor (ER), progesterone receptor (PR), E-cadherin, human epidermal growth factor receptor (HER2), and MIB-1 of 254 ILC cases were retrieved. The patient with ILC and coexisting LCIS were compared with pure ILC cases with respect to different clinicopathologic parameters. RESULTS: Of the 254 cases, 107 cases were pure ILC and 147 cases were ILC with coexisting LCIS. Seventy-six (76/184, 41.32%) cases showed axillary lymph node metastases. Lymph node metastasis was absent in 108 cases, micrometastasis was present in 5 cases, and stage N1, N2, N3 in 51, 5, and 15 cases, respectively. Nodal involvement, locoregional and distant recurrence of ILC with LCIS were less frequent compared with ILC without LCIS with P-value of 0.034 and 0.007, respectively. The presence of coexisting LCIS in ILC predicted higher disease-free survival (DFS) compared with pure ILC (P=0.034, log-rank test). When divided into different strata, ER-positive ILC cases with associated LCIS cases showed better DFS than ER-positive pure ILC cases (P=0.021, log-rank test). Similarly, ILC cases with LCIS in patient less than 50 years showed better DFS than the patient less than 50 years with pure ILC (P=0.045, log-rank test). CONCLUSIONS: In conclusion, ILC coexisting with lobular carcinoma in situ (ILC+LCIS) is characterized by less nodal involvement, lower locoregional, and distant recurrence and better DFS than pure ILC. When divided into different strata, ER-positive and less than 50-year groups with ILC+LCIS show even significant better DFS than pure ILC. These findings suggest that there is biological significance of coexisting LCIS in ILC and that this may have more effect on tumor aggressiveness in certain strata of ILC.

Fine needle aspiration of secondary synovial sarcoma of the thyroid gland.

Synovial sarcomas (SS) of the head and neck region are extremely rare and arise in only 5% of cases. We present a case of secondary SS of the thyroid originally diagnosed as medullary carcinoma on fine needle aspiration (FNA). A 41-year-old man presented with several weeks of dysphonia and a left thyroid mass. FNA of the thyroid nodule showed a cellular smear composed of loosely cohesive oval to spindle-shaped cells with irregular nuclear borders, finely granular chromatin, and inconspicuous nucleoli. The patient was diagnosed with medullary carcinoma and underwent a total thyroidectomy. Intro-operatively, the mass was found to arise from the tracheoesophageal groove with spread to the left thyroid. Microscopic examination of the thyroid tumor revealed a dense spindle cell proliferation with abundant mitoses, scant cords and nests of epithelial cells and foci of necrosis. The spindle cells were positive for bcl2 and vimentin and the epithelial cells were positive for cytokeratin 8/18 and epithelial membrane antigen (EMA). Both spindle and epithelial cells were negative for thyroglobulin, calcitonin, synaptophysin and chromogranin. Fluorescence in situ hybridization (FISH) demonstrated translocation (X;18)(p11;q11), confirming the diagnosis of SS. The patient underwent a total laryngopharyngoesophagectomy with subsequent adjuvant therapy and is currently disease free. Only 6 cases of histologically confirmed primary SS of the thyroid have been reported. To the best of our knowledge, this is the first case of FISH-confirmed secondary SS of the thyroid and also the first case of SS arising from the tracheoesophageal groove.

Myocardial changes in a patient with anorexia nervosa: a case report and review of literature.

OBJECTIVES: Anorexia nervosa (AN) is an eating disorder with high mortality and morbidity. Much of the mortality is related to cardiovascular complications manifesting with electrocardiogram abnormalities and morphologic abnormalities documented on ultrasound. However, gross and histologic abnormalities in the heart have been rarely described in association with this eating disorder. METHODS: We present an autopsy case of an adult patient with AN. We describe the clinical presentation of this patient, as well as significant gross and histologic abnormalities of the heart, and discuss their implications. RESULTS: At autopsy, the heart was small with mainly a small left ventricle. Histologically, we found endocardial and interstitial fibrosis, areas of myxoid material deposition with mast cells in the background, and increased cytoplasmic lipofuscin. CONCLUSIONS: The gross findings in the heart correlate with the previously described anomalies on cardiac ultrasound of patients with AN. The fibrosis and myxoid material deposition might be a direct consequence of starvation and the mechanism of death in some patients with AN.

Anaplastic large cell lymphoma: the most common T-cell lymphoma in pakistan.

OBJECTIVE: To study the prevalence and immunohistochemical profile of the subtypes of anaplastic large cell lymphomas (ALCLs) at a major referral center of Pakistan. METHODS: Epidemiological data for all mature T-cell non-Hodgkin's lymphoma (NHL) diagnosed between 1st January 2005 and 30th June 2010 at the Aga Khan University Department of Histopathology were reviewed and analyzed with SPSS v17.0. RESULTS: A total of 178 specimens were diagnosed as mature T- and NK- cell NHL during the period. Of these 100 (56.2%) were diagnosed as systemic ALCL. These tumors were of either T- or null-cell type with consistent (100%) expression of CD30 (Ki-1). Forty three (43%) cases were further classified as ALK positive, fifty (50%) as ALK negative and seven (7%) were not tested for ALK expression. The mean age of the ALK positive group was 26.7 years as compared to the ALK negative of 35.6 years. The gender ratio of ALK positive cases was 2.3:1 (M:F) as compared to the 2.5:1 ratio seen in the ALK negative cases. There were no significant differences in the nodal and extra-nodal involvement patterns between ALK+ and ALK- groups but epithelial membrane antigen was positive more often in the ALK positive group. CONCLUSION: Compared to other published studies, this proportion of ALCL within the mature T- and NK- cell lymphoma category was found to be alarmingly high and calls for attention. Further studies should be conducted in our region, which in turn would enable clinicians to successfully battle against this neoplastic disease.