Abhijit Chougule

IgG4 related sclerosing mastitis: expanding the morphological spectrum of IgG4 related diseases

Summary IgG4 related disease (IgG4RD) is a recently recognised condition characterised by mass forming lesions associated with storiform fibrosis, obliterative phlebitis, lymphoplasmacytic infiltrate rich in IgG4 positive plasma cells and elevated serum IgG4 levels. Although rare, mammary involvement has been reported as IgG4 related sclerosing mastitis, the morphological counterpart of a growing family of IgG4 related diseases. A total of 17 cases belonging to mass forming benign inflammatory breast lesions such as plasma cell mastitis, granulomatous lobular mastitis, non-specific mastitis and inflammatory pseudotumour were investigated as a possible member of IgG4 related sclerosing mastitis. Clinical, radiological, histopathological and immunohistochemistry findings were noted in all cases. Cases diagnosed as inflammatory pseudotumour showed all the histopathological features of IgG4RD along with increased number of IgG4 positive plasma cells and IgG4/IgG ratio >40%. However, only a few IgG4 positive cells were seen in plasma cell mastitis, granulomatous lobular mastitis and non-specific mastitis cases. These cases also did not fulfill the morphological criteria for the diagnosis of IgG4 related diseases. IgG4RD should be excluded in plasma cell rich lesions diagnosed on core biopsies by IgG4 immunostaining. This can avoid unnecessary surgery as IgG4 related diseases respond to simple and effective steroid treatment.

IgG4-related inflammatory pseudotumor: A systematic review of histopathological features of reported cases

Abstract Objectives: There is marked inconsistency in reporting the key features of IgG4-related inflammatory pseudotumor (IPT) cases. We aimed to analyze the various aspects of IgG4-related IPTs and to test the performance of the consensus criteria for their diagnosis. Methods: PubMed database was searched for IgG4-related IPT cases. The data regarding patient demographics, clinical presentation, laboratory findings, histopathological features, and treatment response are extracted and are presented here in a descriptive manner. Results: The study included 40 papers describing the clinicopathological features of 83 IPTs in 80 patients. Seventeen cases were diagnosed on biopsies; while remaining were diagnosed on excision specimens. Among these, 50 cases were categorized as highly suggestive and 24 cases as probable for IgG4RD; while nine cases had insufficient histopathological evidence of IgG4RD. Two cases diagnosed on biopsies having insufficient evidence of IgG4RD showed partial or no response to steroids; while 12/14 cases (85.71%) diagnosed on biopsies that were histologically suggestive or probable for IgG4RD showed prompt response to steroids. Conclusion: Many reports have not specifically mentioned the full histopathological findings of IgG4-related IPTs that may hinder in refining the diagnostic criteria of IgG4RD. The IgG4-related IPTs diagnosed on biopsies with requisite features showed prompt response to steroids indicating specificity of histopathological findings in predicting treatment response.

A Comparative Study of Inflammatory Myofibroblastic Tumors and Tumefactive IgG4-related Inflammatory Lesions: the Relevance of IgG4 Plasma Cells.

IgG4-related disease is a recently recognized systemic condition characterized by tumefactive lesions at various sites. Inflammatory pseudotumor (IPT), a tumefactive mass lesion with an unknown etiology, belongs to the spectrum of IgG4-related disease. Inflammatory myofibroblastic tumor (IMT), previously considered under the umbrella of IPT, is now classified as a clonal neoplasm. Previously, both the terms were used interchangeably, because of overlapping morphologic features. This study was carried out to compare the morphologic and the immunohistochemical features of these entities and to study the role of IgG4 in their pathogenesis. Thirty-nine cases comprising of IMT (n=18) and IPT (n=21) were retrieved, and their clinical, morphologic, and immunohistochemical features were studied. IMT was more common in children as compared with IPT. IMT cases showed the proliferation of myofibroblastic cells accompanied by a variable inflammatory infiltrate, whereas IPT cases showed predominantly stromal fibrosis and a lymphoplasmacytic infiltrate with a subset of cases showing a storiform fibrosis and obliterative phlebitis. Anaplastic lymphoma kinase-1 (ALK-1) was positive in 12 of the 18 (66.7%) IMT cases, whereas none of the IPT cases showed ALK-1 immunoreactivity. IPT cases showed significantly increased IgG4+ plasma cells (mean, 127.8/high-power fields vs. 17.8/high-power fields) and a higher IgG4/IgG ratio (mean, 48.2% vs. 10.7%) as compared with IMT. Fluorescence in situ hybridization analysis was positive for ALK rearrangement in 6 of the 9 IMT cases tested. In conclusion, most of the IPT cases can be considered as IgG4 related on the basis of their histopathologic features and immunohistochemistry criteria. However, IMT represents a myofibroblastic neoplasm with ALK-1 overexpression and is clearly not IgG4 related.

Pulmonary Gangrene Due to Rhizopus spp., Staphylococcus aureus, Klebsiella pneumoniae and Probable Sarcina Organisms.

Pulmonary gangrene is a life-threatening condition, which represents the fulminant end of the infectious lung diseases usually caused by polymicrobial infection. Aerobic and anaerobic bacteria act synergistically to produce massive tissue necrosis which might be augmented by the angioinvasive nature of fungi like Mucor. We report a successfully treated case of pulmonary gangrene in a poorly controlled diabetic patient, which was associated with polymicrobial infection. It was caused by Rhizopus spp., Staphylococcus aureus, Klebsiella pneumoniae and unusual anaerobic organism Sarcina. This is the first report describing the presence of Sarcina organisms in a case of pulmonary gangrene. Adequate glycemic control, treatment of coexisting polymicrobial infection and prompt antifungal therapy along with surgical intervention were useful in the index patient. This case also highlights the effectiveness of combined medical and surgical intervention in a case of pulmonary gangrene.

Crystalloid granuloma with amylase crystalloids in submandibular gland cytology

Dear Sir, We read with great interest the recent article titled “aamylase crystalloid granuloma in the parotid gland” by Kuwabara et al. They described crystalloid granuloma of parotid gland diagnosed by fine-needle aspiration cytology (FNAC). We also recently came across a similar case in a 48-year-old lady who presented with pain and swelling in the left submandibular region for one month. On examination the swelling was tender, firm, and measured 3 cm 3 2 cm 3 2 cm. The overlying skin was normal in appearance and there was no facial nerve palsy. A clinical diagnosis of chronic sialadenitis was made and FNA was requested to confirm the diagnosis. FNA yielded light brown gritty material from which air-dried as well as ethanol-fixed smears were made. Microscopic examination of the smears revealed abundant extra as well as intracellular crystalloids which were cuboidal to elongated (50–100 lm long), rhomboid, multifaceted, non-birefringent, and dark blue on routine Giemsa stain (Fig. 1A), orangeophilic on Papanicolaou stain (Fig. 1B), and eosinophilic on hematoxylin and eosin stain (Figs. 1C and D). There was a florid foreign body type granulomatous reaction to the crystalloids (Fig. 1C) consisting of lymphocytes, histiocytes, and many epithelioid cell granulomas with multinucleated giant cells containing phagocytosed crystalloids (Fig. 1D). Focal areas showed a prominent neutrophilic response with many degenerating cells in the background. Occasional clusters of salivary acinar and ductal cells were also seen. Based on cytomorphology, the case was reported as chronic sialadenitis with crystalloid granuloma. No treatment was given. A second FNA performed three weeks later revealed a similar picture. However, it was less severe and after a month, the swelling resolved after a course of antibiotics. Since the first report of crystalloids in salivary glands by Takeda and Ishikawa in 1983, over fifty such cases have been reported by various authors. While most authors describe a neutrophilic response, rarely these crystalloids induce a florid granulomatous reaction. The present case showed prominent granulomatous reaction with the presence of many scattered multinucleated giant cells containing phagocytosed crystalloids. This case, which shows relatively similar cytomorphological features to that described by Kuwabara et al., is the first reported in a submandibular salivary gland FNA and therefore brings total number of crystalloid granuloma cases to 6. It is likely that such a response occurs following rupture of salivary ducts and release of the crystalloids into the salivary gland parenchyma inducing florid granulomatous response. The a-amylase crystalloids in salivary glands are reported to be associated with both non-neoplastic and rarely neoplastic lesions. The exact significance of these crystalloids on FNA is therefore difficult to predict. These crystalloids are formed due to supersaturation of saliva in the dilated ducts. Compared to parotid gland, sialolithiasis and sialadenitis are more common in submandibular glands because of the upward course of the submandibular duct leading to stasis of secretions. On the other hand, crystalloid granulomas are observed more frequently in the parotid gland as it is the major producer of serous fluid rich in amylase. Crystalloid formation occurred in the submandibular gland in the index case and is explained by the fact that it is a sero-mucinous gland with a significant proportion of serous units. The extent to which infectious agents are responsible for the formation of crystalloids is not clear, as some cases show resolution following a course of antibiotics, some resolve spontaneously and some recur in spite of antibiotic use and require surgical excision. All the previously reported crystalloid granuloma cases underwent *Correspondence to: Dr. Radhika Srinivasan, MD, PhD, Professor, Department of Cytology and Gynaec Pathology, Post graduate Institute of Medical Education and Research, Chandigarh, India, 160012. E-mail: drsradhika@gmail.com Received 27 May 2015; Revised 30 July 2015; Accepted 24 September 2015 DOI: 10.1002/dc.23384 Published online 15 October 2015 in Wiley Online Library (wileyonlinelibrary.com).

Uncommon associations and catastrophic manifestation in Takayasu arteritis: an autopsy case report

Takayasu arteritis, a chronic inflammatory vasculitis affecting aorta and its major branches, is complicated by stenosis, occlusion, and aneurysm formation. The aneurysm formation and subsequent complications such as heart failure, aortic regurgitation, and aneurysm rupture can be fatal. The aortic aneurysm rupture is a rare and fatal complication with only a few cases reported in the English literature. The involvement of coronary artery in Takayasu occurs in about 10% patients, and the coronary artery aneurysm is the least common manifestation. Here, we describe a case of Takayasu arteritis with abdominal aortic aneurysm rupture and coronary artery aneurysm. This patient also had associated systemic inflammatory diseases like sarcoidosis and Hashimotos thyroiditis.

A Long-Standing Primary Vaginal Paraganglioma—Coexisting with Esophageal Carcinoma

Sir, Paraganglioma is a rare neoplasm derived from the neural crest cells residing in the paraganglia of the autonomic nervous system. Primary vaginal paraganglioma is extremely rare. [1]. Herein, we present a unique case of a vaginal paraganglioma which was radiologically interpreted as a metastatic nodule in a young female, which is a known case of esophageal carcinoma. A 28-year-old married female presented with dysphagia to solid foods was diagnosed as having keratinizing squamous cell carcinoma of the lower esophagus on biopsy 5 years back. She received neoadjuvant chemoradiotherapy (NACRT). Post-NACRT PET-CT revealed moderate to intense FDG (flurodeoxyglucose) uptake with decline in SUV max to 6.7 indicating a favorable response to chemotherapy. However, PET-CT revealed an intense FDG-avid (SUV max = 20.9) homogeneous soft tissue lesion measuring 2.1 × 2.1 cm in the left lateral vaginal wall with well-maintained fat planes with the adjacent urinary bladder wall (Fig. 1a). On pervaginum examination, a firm, well-defined mass measuring 2 × 3 cm was noted along the middle one-third of the left lateral vaginal wall, though she did not have any gynecological complaints. Fine-needle aspiration cytology (FNAC) from the vaginal mass did not reveal any malignant cells, and the cells were interpreted as histiocytes. Following this, she underwent trans-hiatal esophagectomy which confirmed the diagnosis of keratinizing squamous cell carcinoma. Her follow-up PET-CT scan post-surgery showed similar FDG uptake in the vaginal mass, without any increase in its size. However, the most recent PET-CT scan showed increase in the FDG uptake. Contrast-enhanced computed tomography (CECT) showed the vaginal lesion to be heterogeneously enhancing soft tissue mass measuring 3.6 × 2 cm with increased vascularity and a clinical possibility of metastatic tumor deposit was favored. USGguided FNAC from the mass revealed predominantly blood along with few histiocytic collections (Fig. 1b). Finally, the mass was surgically excised and the vaginal wall was reconstructed. Grossly, it measured 3 × 3 cm and had a firm and brown-colored cut-surface. On microscopic examination, the tumor exhibited a classical Zellballen pattern comprising of nests and islands of tumor cells with a prominent intervening fibrovascular stroma (Fig. 1c). The tumor cells were large and polygonal shaped with fine-stippled chromatin, inconspicuous nucleoli, and abundant granular eosinophilic to clear cytoplasm with well-defined cell membranes. Tumor cell nests were bordered by few spindle-shaped sustentacular cells (Fig. 1a). At the periphery, the blood vessels were evenmore prominent and hyalinized. No mitosis or necrosis was noted. On IHC, the tumor cells were strongly positive for chromogranin (Fig. 1d), synaptophysin (Fig. 1e), neuron-specific enolase (NSE), and CD 56. S-100 protein highlighted the sustentacular cells (Fig. 1f), and pan-cytokeratin was negative. Based on these morphological features, a diagnosis of primary vaginal paraganglioma was made. Retrospective review of FNAC smears revealed few singly scattered tumor cells with round nuclei and abundant granular cytoplasm consistent with * Rashi Garg rashiigarg@gmail.com

Cutaneous metastasis from a myoepithelial carcinoma of submandibular salivary gland

Myoepithelial carcinoma is a rare malignant tumor of salivary gland with locally aggressive nature and potential for distant metastasis. It is composed of tumor cells with myoepithelial differentiation showing varied cytomorphology. Lungs and kidneys are the commonest sites for distant metastasis. Cutaneous metastasis of myoepithelial carcinoma is very rare. In this report, we described cutaneous metastasis of myoepithelial carcinoma arising from submandibular gland. Diagn. Cytopathol. 2015;43:53–56.

Primary renal vein leiomyosarcoma: a case report

Primary renal vein leiomyosarcoma (LMS) is a rare tumor with only a few cases reported in the literature. Clinical diagnosis of renal vein LMS can be difficult because of nonspecific symptoms and nonpathognomonic radiological features. The primary treatment modality is radical nephrectomy followed by chemotherapy and/or radiotherapy. There is scarcity of literature regarding prognosis because of rarity of tumor; however, tumor size (>3 cm) determines the risk of local recurrence and distant metastasis. Overall prognosis of renal vein LMS is poor. Here, we describe clinical and histopathological features of a 50-year-old female patient with LMS of right renal vein.