Mammary Filariasis • 549
of ADH and low grade ductal carcinoma in-situ (DCIS) arising from a complex sclerosing lesion, involved by secretory endometrium-like changes. Tavassoli et al. described similar secretory endometrium-like epithelium involving intraductal papillary carcinoma. Several foci of atypical epithelial proliferation lacking fibrovascular support were also described. Similar to our case, the myoepithelial cell layer was described to be absent in much of the lesion. The presence subnuclear vacuolization, both within DCIS, and in adjacent benign ducts, is of uncertain significance. It is possible that, as Tavassoli et al. noted, it simply represents an unusual morphologic variant superimposed on a pre-existing benign, atypical, or malignant process, as our case demonstrates. It should be noted, however, that the presence of a variant of invasive ductal carcinoma with secretory
endometrium-like subnuclear vacuolization has not, to our knowledge, been described. Further studies into the nature of this distinctive entity are required to clarify its significance. Acknowledgments We thank Dr. Sally T. Turla, D.O., Kaiser Permanente, West Los Angeles Medical Center, Los Angeles, CA, USA for sending this consultation case.
FUNDING The authors declare that no funds were received from any source for this study and no conflicts of interest.
Mammary Filariasis Masquerading as Breast Carcinoma Prasad Dange, MBBS, Garima Goel, MD, Nivedita Ghosh, MD, Shipra Agarwal, MD, Seema Kaushal, MD, and Shyama Jain, MD Department of Pathology, Maulana Azad Medical, College and Lok Nayak Hospital, New Delhi, India
A
60-year female presented with a lump in the right breast for 8 months. On examination, the ill defined lump was in the lower outer quadrant, it was nonmobile, firm, tender, and measured 5 9 4 cm in size; overlying skin was erythematous, discolored, and indurated (Fig. 1a). There were no lumps in the contra lateral breast and both axillae. Clinical diagnosis was highly suspicious of a malignancy. Radiologically, mammography showed diffuse asymmetric increased density in right breast suggestive of BIRADS 3; MRI revealed diffusely thickened right breast parenchyma which was heterogeneously hyper intense on ShortTau-Inversion-Recovery (STIR) sequence, and hypointense on T1 weighted image; no obvious focal mass lesion was observed, thus findings were suggestive of benign etiology (Fig. 1b–e).
The patient was referred for FNAC. Giemsa stained smears showed mainly inflammation including neutrophils, eosinophils, few granulomas along with
(a)
(b) Address correspondence and reprint requests to: Dr. Shyama Jain, MD, Director Professor & Head, Department of Pathology, Maulana Azad Medical College, New Delhi 110002, India, or e-mails: [email protected]; [email protected] DOI: 10.1111/tbj.12318 © 2014 Wiley Periodicals, Inc., 1075-122X/14 The Breast Journal, Volume 20 Number 2, 2014 549–551
(d)
(c)
(e)
Figure 1. Clinical photograph (a), showing grossly involved right breast with overlying erythematous, discolored and indurated skin; Mammaography (b and c) showing diffuse asymmetric increased density in right breast (b), normal breast (c); MRI showing diffuse thickened parenchyma with heterogenous hyper-intense right breast on STIR sequence (d), and hypointense on T1 weighted image (e).
550 • dange et al.
(b)
(b)
(d)
(a)
(c)
(d)
Figure 2. FNA Breast: Clusters of breast epithelial cell along with aggregates of polymorphs and eosinophils (a), lympho-histiocytic clusters and granuloma (b and c) microfilariae near epithelial cluster (d), High power showing MF (e) with sheathe (unstained), pointed tail end with nuclei lagging behind the tail tip (arrow). Giemsa stain 9250 (a–d), 400 (e).
many microfilaria of Wuchereria bancrofti species. Also seen were clusters of mildly pleomorphic breast epithelial cells in a focal acinar pattern (Fig. 2). There was no necrosis or mitosis, thus the cytologic diagnosis was of Mammary Filariasis (MF). Further trucut biopsy from the lump revealed clusters of benign breast epithelial cells and fragmented body parts of an adult filarial worm (AFW) cut in several planes with coiled and uncoiled MF within the filarial uterine cavity, along with dense inflammation comprising of histiocytes, eosinophils and lympho-plasmacytic cells (Fig. 3).The findings were consistent with the cytologic diagnosis of MF. On further examination, both the lower extremities and the vulva were nonedematous and, there was no history suggestive of chyluria. The hematological work up revealed increased absolute eosinophil count (1,210 cells/mm3). Thus, the final diagnosis was of a rare and interesting case of MF and the patient was started on Diethylcarbamazepine (DEC). Filariasis is a major health problem in tropical countries and is endemic in many areas of India, Africa, and Far East. W. bancrofti accounts for ~90% of filariasis cases in the world followed by Brugia malayi and B. timori. These nematodes dwell mostly in the soft tissues, lymphatics of lower limbs, retroperitoneum, scrotum, and rarely breast. The host tissue response to the parasites is extremely variable and ranges from an insignificant reaction to marked inflammation, histiocytic collections and granuloma formation.
(a)
(c)
Figure 3. Biopsy breast: (a) Gravid female filarial worm with outer serrated. Integument (Thick arrow), uterine segment in body cavity with MF (hollow arrow), inflammatory background (thin arrow); (b and c) showing many coiled and uncoiled MF in the uterine segment. H & E stain 9250 (a), 400 (b and c).
Filariasis is characterized by the presence of tissue microfilaria, which is free-living embryo. They may be sheathed or unsheathed, this and nuclear arrangement in the tail end helps in species differentiation. AFW of different species also show different morphology, showing a small intestine, a much larger single testis in males and two ovaries in females. They live in lymphatics, lymph nodes, soft tissues, and body cavities. W. bancrofti has been reported at different sites (breast, thyroid, lymph nodes, liver, lungs, and body fluids). MF is an extremely rare condition and only few cases have been reported in the published literature. It is prevalent in areas endemic for W. bancrofti i.e., India and Srilanka. The patients of MF usually present with solitary, painless, unilateral breast lump, upper-outer quadrant being the most common site. The lesions involve the subcutis and present as a hard mass with associated induration, inflammation, edema, and even adherence to the overlying skin; thus, simulating a malignant lesion. The diagnosis of MF depends on specific microscopic features of adult worm and microfilariae. In the present case, mammographic findings were nonspecific and microfilariae could not be demonstrated in the night smears. FNA smear of the breast lump demonstrated the microfilariae and granulomas while the trucut biopsy revealed fragmented AFW with gravid uterus, microfilariae, and tissue eosinophilia. To conclude, the present case is interesting since clinically it simulated malignancy; however cytology
Breast MALToma • 551
and trucut biopsy were diagnostic of filariasis that helped in appropriate therapeutic management, thus avoiding unnecessary surgery.
CONFLICTS OF INTEREST None declared.
Breast MALToma Yiming Qian, MD,* Jean Seely, MD,† Shaheed Hakim, MD,‡ Bruce M. Jamison, MDCM,‡ and Angel Arnaout, MD§ *Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada; †Division of Breast Imaging, Ottawa Hospital Women’s Breast Health Centre, Ottawa, Ontario, Canada; ‡Department of Pathology and Laboratory Medicine, University of Ottawa, Ottawa, Ontario, Canada; § Department of Surgery, University of Ottawa, Ottawa, Ontario, Canada
A
57-year-old Caucasian female presented to her primary care physician with a painless lump in her left breast that she had noticed for the past few months. She did not have any significant risk factors for breast cancer, and her family history was significant only for colon cancer. The patient denied any chest pain, dyspnea, cough, or hemoptysis. No nausea, vomiting, or dysphagia was noted but she did complain of 2-month history of left flank pain. No B type symptoms were reported. Past medical history was significant for Hepatitis C infection and bilateral subglandular silicone breast implants from several years ago. The patient denied any history of autoimmune diseases or known H.pylori infection. Physical exam revealed a vague palpable 2 cm mass at the 3:00 position of her left breast with a palpable mobile left axillary node. There were no skin or nipple changes. Assessment of cervical or supraclavicular nodal basin was negative. Abdominal examination revealed splenomegaly. She was investigated initially with mammography that showed a conspicuous and irregularly shaped 2 cm nodule free of calcifications at the 3:00 position of her left breast, lateral and slightly posterior to the breast implant in the left outer quadrant (Fig. 1a and b). Doppler Sonography demonstrated vascular integrity within the hypoechoic and irregularly shaped mass that measures 1.7 cm 9 1.5 cm
Address correspondence and reprint requests to: Angel Arnaout, MD, Department of Surgery, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada, or e-mail: [email protected] DOI: 10.1111/tbj.12313 © 2014 Wiley Periodicals, Inc., 1075-122X/14 The Breast Journal, Volume 20 Number 2, 2014 551–552
(Fig. 1c). This phenomenon raised the suspicion for breast lymphoma albeit an uncommon differential diagnosis. An ultrasound-guided core biopsy of the breast mass and axillary node was performed. Pathologic analysis of both specimens was similar and demonstrated extensive lymphoid infiltrate. Immunohistochemical analysis was positive for CD20 and CD43 and negative for CD5, CD10, and Bcl-6 with kappa restriction. The result substantiates the diagnosis of an indolent extranodal marginal zone lymphoma also known as MALToma. Polymerase chain reaction (PCR) analysis of the paraffin embedded tissue showed evidence of two clonal (FR1 and FR2) immunoglobulin heavy chain (IgH) gene rearrangements, in keeping with the diagnosis. To stage the disease, CT head and neck, thorax and abdomen were done. They showed the left breast lesion (Fig. 1d), an enlarged left axillary lymph node, an 8 mm 9 6 mm peribronchial lung nodule in the right upper lobe, moderate splenomegaly and two nonspecific subcutaneous soft tissue nodules. According to Ann Arbor classification system for all lymphomas, the patient in this case report is stage IVa due to breast, spleen, lung involvement, and lack of constitutional symptoms. The case was discussed in detail at the multidisciplinary round. Patient has been referred to medical oncology for treatment and follow-up. The treatment for advanced lymphoma is systemic with a combination of chemotherapy and immunotherapy. She was started on a 6-month regimen of Bendamustine (an alkylating chemotherapy agent) and Rituximab
of ADH and low grade ductal carcinoma in-situ (DCIS) arising from a complex sclerosing lesion, involved by secretory endometrium-like changes. Tavassoli et al. described similar secretory endometrium-like epithelium involving intraductal papillary carcinoma. Several foci of atypical epithelial proliferation lacking fibrovascular support were also described. Similar to our case, the myoepithelial cell layer was described to be absent in much of the lesion. The presence subnuclear vacuolization, both within DCIS, and in adjacent benign ducts, is of uncertain significance. It is possible that, as Tavassoli et al. noted, it simply represents an unusual morphologic variant superimposed on a pre-existing benign, atypical, or malignant process, as our case demonstrates. It should be noted, however, that the presence of a variant of invasive ductal carcinoma with secretory
endometrium-like subnuclear vacuolization has not, to our knowledge, been described. Further studies into the nature of this distinctive entity are required to clarify its significance. Acknowledgments We thank Dr. Sally T. Turla, D.O., Kaiser Permanente, West Los Angeles Medical Center, Los Angeles, CA, USA for sending this consultation case.
FUNDING The authors declare that no funds were received from any source for this study and no conflicts of interest.
Mammary Filariasis Masquerading as Breast Carcinoma Prasad Dange, MBBS, Garima Goel, MD, Nivedita Ghosh, MD, Shipra Agarwal, MD, Seema Kaushal, MD, and Shyama Jain, MD Department of Pathology, Maulana Azad Medical, College and Lok Nayak Hospital, New Delhi, India
A
60-year female presented with a lump in the right breast for 8 months. On examination, the ill defined lump was in the lower outer quadrant, it was nonmobile, firm, tender, and measured 5 9 4 cm in size; overlying skin was erythematous, discolored, and indurated (Fig. 1a). There were no lumps in the contra lateral breast and both axillae. Clinical diagnosis was highly suspicious of a malignancy. Radiologically, mammography showed diffuse asymmetric increased density in right breast suggestive of BIRADS 3; MRI revealed diffusely thickened right breast parenchyma which was heterogeneously hyper intense on ShortTau-Inversion-Recovery (STIR) sequence, and hypointense on T1 weighted image; no obvious focal mass lesion was observed, thus findings were suggestive of benign etiology (Fig. 1b–e).
The patient was referred for FNAC. Giemsa stained smears showed mainly inflammation including neutrophils, eosinophils, few granulomas along with
(a)
(b) Address correspondence and reprint requests to: Dr. Shyama Jain, MD, Director Professor & Head, Department of Pathology, Maulana Azad Medical College, New Delhi 110002, India, or e-mails: [email protected]; [email protected] DOI: 10.1111/tbj.12318 © 2014 Wiley Periodicals, Inc., 1075-122X/14 The Breast Journal, Volume 20 Number 2, 2014 549–551
(d)
(c)
(e)
Figure 1. Clinical photograph (a), showing grossly involved right breast with overlying erythematous, discolored and indurated skin; Mammaography (b and c) showing diffuse asymmetric increased density in right breast (b), normal breast (c); MRI showing diffuse thickened parenchyma with heterogenous hyper-intense right breast on STIR sequence (d), and hypointense on T1 weighted image (e).
550 • dange et al.
(b)
(b)
(d)
(a)
(c)
(d)
Figure 2. FNA Breast: Clusters of breast epithelial cell along with aggregates of polymorphs and eosinophils (a), lympho-histiocytic clusters and granuloma (b and c) microfilariae near epithelial cluster (d), High power showing MF (e) with sheathe (unstained), pointed tail end with nuclei lagging behind the tail tip (arrow). Giemsa stain 9250 (a–d), 400 (e).
many microfilaria of Wuchereria bancrofti species. Also seen were clusters of mildly pleomorphic breast epithelial cells in a focal acinar pattern (Fig. 2). There was no necrosis or mitosis, thus the cytologic diagnosis was of Mammary Filariasis (MF). Further trucut biopsy from the lump revealed clusters of benign breast epithelial cells and fragmented body parts of an adult filarial worm (AFW) cut in several planes with coiled and uncoiled MF within the filarial uterine cavity, along with dense inflammation comprising of histiocytes, eosinophils and lympho-plasmacytic cells (Fig. 3).The findings were consistent with the cytologic diagnosis of MF. On further examination, both the lower extremities and the vulva were nonedematous and, there was no history suggestive of chyluria. The hematological work up revealed increased absolute eosinophil count (1,210 cells/mm3). Thus, the final diagnosis was of a rare and interesting case of MF and the patient was started on Diethylcarbamazepine (DEC). Filariasis is a major health problem in tropical countries and is endemic in many areas of India, Africa, and Far East. W. bancrofti accounts for ~90% of filariasis cases in the world followed by Brugia malayi and B. timori. These nematodes dwell mostly in the soft tissues, lymphatics of lower limbs, retroperitoneum, scrotum, and rarely breast. The host tissue response to the parasites is extremely variable and ranges from an insignificant reaction to marked inflammation, histiocytic collections and granuloma formation.
(a)
(c)
Figure 3. Biopsy breast: (a) Gravid female filarial worm with outer serrated. Integument (Thick arrow), uterine segment in body cavity with MF (hollow arrow), inflammatory background (thin arrow); (b and c) showing many coiled and uncoiled MF in the uterine segment. H & E stain 9250 (a), 400 (b and c).
Filariasis is characterized by the presence of tissue microfilaria, which is free-living embryo. They may be sheathed or unsheathed, this and nuclear arrangement in the tail end helps in species differentiation. AFW of different species also show different morphology, showing a small intestine, a much larger single testis in males and two ovaries in females. They live in lymphatics, lymph nodes, soft tissues, and body cavities. W. bancrofti has been reported at different sites (breast, thyroid, lymph nodes, liver, lungs, and body fluids). MF is an extremely rare condition and only few cases have been reported in the published literature. It is prevalent in areas endemic for W. bancrofti i.e., India and Srilanka. The patients of MF usually present with solitary, painless, unilateral breast lump, upper-outer quadrant being the most common site. The lesions involve the subcutis and present as a hard mass with associated induration, inflammation, edema, and even adherence to the overlying skin; thus, simulating a malignant lesion. The diagnosis of MF depends on specific microscopic features of adult worm and microfilariae. In the present case, mammographic findings were nonspecific and microfilariae could not be demonstrated in the night smears. FNA smear of the breast lump demonstrated the microfilariae and granulomas while the trucut biopsy revealed fragmented AFW with gravid uterus, microfilariae, and tissue eosinophilia. To conclude, the present case is interesting since clinically it simulated malignancy; however cytology
Breast MALToma • 551
and trucut biopsy were diagnostic of filariasis that helped in appropriate therapeutic management, thus avoiding unnecessary surgery.
CONFLICTS OF INTEREST None declared.
Breast MALToma Yiming Qian, MD,* Jean Seely, MD,† Shaheed Hakim, MD,‡ Bruce M. Jamison, MDCM,‡ and Angel Arnaout, MD§ *Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada; †Division of Breast Imaging, Ottawa Hospital Women’s Breast Health Centre, Ottawa, Ontario, Canada; ‡Department of Pathology and Laboratory Medicine, University of Ottawa, Ottawa, Ontario, Canada; § Department of Surgery, University of Ottawa, Ottawa, Ontario, Canada
A
57-year-old Caucasian female presented to her primary care physician with a painless lump in her left breast that she had noticed for the past few months. She did not have any significant risk factors for breast cancer, and her family history was significant only for colon cancer. The patient denied any chest pain, dyspnea, cough, or hemoptysis. No nausea, vomiting, or dysphagia was noted but she did complain of 2-month history of left flank pain. No B type symptoms were reported. Past medical history was significant for Hepatitis C infection and bilateral subglandular silicone breast implants from several years ago. The patient denied any history of autoimmune diseases or known H.pylori infection. Physical exam revealed a vague palpable 2 cm mass at the 3:00 position of her left breast with a palpable mobile left axillary node. There were no skin or nipple changes. Assessment of cervical or supraclavicular nodal basin was negative. Abdominal examination revealed splenomegaly. She was investigated initially with mammography that showed a conspicuous and irregularly shaped 2 cm nodule free of calcifications at the 3:00 position of her left breast, lateral and slightly posterior to the breast implant in the left outer quadrant (Fig. 1a and b). Doppler Sonography demonstrated vascular integrity within the hypoechoic and irregularly shaped mass that measures 1.7 cm 9 1.5 cm
Address correspondence and reprint requests to: Angel Arnaout, MD, Department of Surgery, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada, or e-mail: [email protected] DOI: 10.1111/tbj.12313 © 2014 Wiley Periodicals, Inc., 1075-122X/14 The Breast Journal, Volume 20 Number 2, 2014 551–552
(Fig. 1c). This phenomenon raised the suspicion for breast lymphoma albeit an uncommon differential diagnosis. An ultrasound-guided core biopsy of the breast mass and axillary node was performed. Pathologic analysis of both specimens was similar and demonstrated extensive lymphoid infiltrate. Immunohistochemical analysis was positive for CD20 and CD43 and negative for CD5, CD10, and Bcl-6 with kappa restriction. The result substantiates the diagnosis of an indolent extranodal marginal zone lymphoma also known as MALToma. Polymerase chain reaction (PCR) analysis of the paraffin embedded tissue showed evidence of two clonal (FR1 and FR2) immunoglobulin heavy chain (IgH) gene rearrangements, in keeping with the diagnosis. To stage the disease, CT head and neck, thorax and abdomen were done. They showed the left breast lesion (Fig. 1d), an enlarged left axillary lymph node, an 8 mm 9 6 mm peribronchial lung nodule in the right upper lobe, moderate splenomegaly and two nonspecific subcutaneous soft tissue nodules. According to Ann Arbor classification system for all lymphomas, the patient in this case report is stage IVa due to breast, spleen, lung involvement, and lack of constitutional symptoms. The case was discussed in detail at the multidisciplinary round. Patient has been referred to medical oncology for treatment and follow-up. The treatment for advanced lymphoma is systemic with a combination of chemotherapy and immunotherapy. She was started on a 6-month regimen of Bendamustine (an alkylating chemotherapy agent) and Rituximab
