DOI: https://doi.org/10.21203/rs.3.rs-1994957/v1
Introduction: Nodular hidradenoma is a rare and very slow-growing tumor of the sweat gland; it is also known as clear cell hidradenoma/clear cell myoepithelioma or eccrine acrospiroma. Due to cystic nature the neoplasm it can masquerade as cystic lesion.
Case Presentation :We present a case of a middle-aged Asian female who complaint of a slightly mobile lump in the left breast. The clinical suspicion of fibroadenoma was made, and the lesion was excised. The histopathological features were of nodular hidradenoma. The three years follow-up was uneventful.
Conclusions: Nodular hidradenoma is rare in the breast and lacks characteristic clinical and radiological features. They share similar features as reported elsewhere in the body. Therefore, the final diagnosis is mainly made only after the histopathological examination.
Nodular hidradenoma (NH) is a rare eccrine sweat gland tumor. With an extensive literature search, less than thirty-five cases have been reported in the indexed English literature.[ 1–28]
Clear cell hidradenoma shares similar features reported elsewhere in the body like axillae, face, arms, thighs, trunk, scalp, and pubic region. [14]
Nodular hidradenoma can be located deep within the parenchyma of the breast tissue with no relation to the overlying skin or they can be superficially located in the nipple region.[8] These tumors can be the differential diagnosis for the tumor of the subareolar region of the breast. Superficial lesion arises from the skin adnexal glands while the deep lesion arises from the mammary ducts in the breast. [18] Due to cystic nature the neoplasm it can masquerade as cystic lesion.
A 40-year-old female came to the surgeryoutpatient department with complaint of a lump in the left breast for four months. No skin ulcer or nipple abnormality was present on local examination. There was no family history of any breast lesion. The patient was advised for FNAC, mammogram ultrasound examination. The ultrasound revealed a solid cystic, oval, well-circumscribed, high-density mass in the upper outer quadrant without any microcalcifications. (Fig. 1a,b,c)
Direct FNA showed cyst macrophages and a few cohesive clusters of epithelial cells on a proteinaceous background. These features were consistent with a cystic lesion. However, USG guided FNA/core needle biopsy was advised to rule out the possibility of low-grade cystic neoplasm. An excision biopsy was done, and a skin-bearing cystic, solid tissue measuring 2.5x1.5x2cm was received for histopathological examination. The skin ellipse measured 2.5x1.3cm, and the underlying solid cystic mass was 1.6 cm in its longest axis. (Fig. 2)
The histopathological examination showed skin with an underlying cyst (Fig. 3a) and a solid area comprised of tumor cells. The dermis showed normal acini, ducts (Fig. 3b) and an encapsulated tumor comprised of lobules of tumor cells separated by fibrous septa. The cells were mildly pleomorphic, with fine chromatin and moderate cytoplasm. The solid areas showed two types of cells: (i) round to polyhedral cells with finely granular faintly eosinophilic cytoplasm with a round to oval nucleus, and (ii) the second population of cells has clear cytoplasm and a small eccentric nucleus with eosinophilic hyalinizing stroma. (Fig. 3c) The cysts were lined by dark cuboidal epithelium. Many entrapped tubules also noted among tumor cells. (Fig. 3d) No significant atypia /mitosis/necrosis was present. The tumor cells were immunoreactive to pan-cytokeratin, ( Fig. 4a) negative to ER (Fig. 4b), SMA and S-100 and intensely reactive to EMA (Fig. 4c), focally reactive to vimentin (Fig. 4d). Features were of Clear cell Nodular Hidradenoma. Patient is doing well at three year of follow up and evidence of any recurrence clinically as well as on imaging.
Skin adnexal neoplasm can occur in the breast, and the other benign skin adnexal tumors reported in the breast are eccrine spiradenoma, syringoma, papillary syringocystadenoma, and cylindroma. After searching on Google Scholar and PubMed using the keywords “nodular hidradenoma breast” and “eccrine acrospiroma breast”, we retrieved 33 cases of nodular hidradenoma of the breast reported in the indexed English literature. (Table 1)
| First author/ Year of publication | Age (years)/sex | Clinical Presentation | Laterality | Duration | Size of lump | Cystic area | |
|---|---|---|---|---|---|---|---|
| 1 | Fink et al. / 1968 | 46 / Female | Nipple discharge with breast mass present in the upper inner quadrant | Not mentioned | 17 years | 10 cm | Present |
| 2 | Fink et al. / 1968 | 61 / Female | Breast lump in the upper outer quadrant | Right | Three years | 3 cm | Present |
| 3 | Fink et al. / 1968 | 42 / Male | Asymmetry of nipples, the tumor is a subareolar region. | Left | Not mention clearly (Many years) | 2 cm | Not mention |
| 4 | Fink et al. / 1968 | 45 / Female | Serous nipple discharge | Left | 8 Months | 0.7 cm | Not mention |
| 5 | Fink et al. / 1968 | 60 / Female | Lump in the subareolar region | Not mentioned | 15 Years | Not mention | Not mention |
| 6 | Fink et al. / 1968 | 30 / Female | Lump in the subareolar region | Right | Not mention | 1 cm | Not mention |
| 7 | Hertel et al. / 1976 | 57 / Female | subareolar mass | Not mentioned | Two weeks | 2 cm | Not mention |
| 8 | Ilie B / 1986 | 73 / Male | Lump in Breast | Left | Several months | 2. cm | Present |
| 9 | Kobayashi et al. / 1994 | 63 / Male | Bloody Nipple discharge and mass | Left | Not mention | 3 cm | Present |
| 10 | Cyrlak et al. / 1995 | 21 / Female | Mass in inner quadrant | Right | One year | 7 cm | Present |
| 11 | Kaise et al. / 1996 | 52 / Female | Lump in upper inner quadrant | Left | NA | ---- | Article not retrieved |
| 12 | Kumar et al. / 1996 | 75 / Female | Lump in breast upper, inner quadrant | Left | Six weeks | 3 cm | Not mention |
| 13 | Domoto et al. / 1998 | 58 / Female | Fluctuating nodule without tenderness | Left | One year | 3 cm | Present |
| 14 | Domoto et al. / 1998 | 44/ Male | Nodule, nipple, discharge | Left | One year | 2 cm | Not Mentioned |
| 15 | Shimizu et al. / 1999 | 60 / Male | Lump in the subareolar area | Right | Not mentioned | 3.5 cm | Present |
| 16 | Yamada et al. / 2001 | 41 / Female | Lump in upper outer | Left | Not mentioned | 2.0 cm | Present |
| 17 | Honma et al. / 2002 | 77 / Male | Nodule beneath in nipple | Not mentioned | Not mentioned | Not Mentioned | Article not retrieved |
| 18 | Kim et al. / 2005 | 41 / Female | Lump in upper inner | Right | One month | 1.5 cm | Not Mentioned |
| 19 | Girish et al. / 2006 | 49 / Female | Lump in the subareolar area | Left | Three years Recurrent | 3 cm | Present |
| 20 | Dhingra et al. / 2007 | 60 / Female | Lump in upper outer | Right | One year | 5.5 cm | Present |
| 21 | Kazakov et al. / 2007 | 55 / Female | Nodule in upper outer | Left | Six months | 2.2 cm | Present |
| 22 | Ohi et al. / 2007 | 55 / Female | Lump in Upper Inner Quadrant | Right | Not mentioned | 0.8 cm | Present |
| 23 | Mote et al. / 2009 | 40 / Female | Lump in upper outer | Left | Two years | 5 cm | Present |
| 24 | Grampurohit et al. / 2011 | 18 / /Male | Painful lump subareolar area, Nipple discharge | Left | Two months | 4 cm | Present |
| 25 | Ives et al. / 2013 | 67 / Female | Nodule near scar | Right | One year | 1 cm | Present |
| 26 | Orsaria M / 2013 | 39/Male | Recurrent Nodule | Left | Recurrent | 1 cm | Not Mentioned |
| 27 | Sehgal et al. / 2014 | 30 / Female | Lump in upper outer | Left | 10 Months | 3 cm | Present |
| 28 | Vasconcelos et al. / 2015 | 40/ Female | Lump in the subareolar area | Right | Five years | 5 cm | Present |
| 29 | Sharma et al. / 2016 | 50/ Female | Lump in Breast | Left | Not mentioned | 3.4 cm | Present |
| 30 | Hsieh et al / 2017 | 50/ Female | Lump in upper outer | Left | 15 years | 3 cm | Present |
| 31 | Yılmaz/2017 | 38 /Female | Lump in the subareolar region | Left | Not mentioned | 3cm | Present |
| 32 | Tynski et al / 2018 | 51/ Female | Lump in Breast | Left | Two years | 2.3 cm | Present |
| 33 | Choi/2019 | 66 /Female | Lump in Breast | Right | Two years | 2.2cm | Present |
| 34 | Jaitly V/2019 | 20/Female | Breast mass | Right | 1 Year | 4cm | Present |
The published data in indexed English literature shows female preponderance accounting76% of the cases. Very few cases of male breast have been reported. [1, 3, 4, 8, 9, 11, 18, 20] The most common presentation is breast lump (97%) and nipple discharge (15%). One case presented with only nipple discharge. [1] Left predominance was seen over the right breast in females (56%).[1,3,4,6,7,8,10,13,15,17,18,20,21,23−26] The duration of complaints was more than one year in 26% of the cases,[1, 13, 17, 22, 24, 26, 27] while it was unknown in (29.4%) of cases. The size of the lump ranged from 0.7 to 10cm. One patient complaint of 10cm lump for 17 years. 1 The imaging showed cystic component in (67.6%) of cases,[1,3,4,5,8,9,10,13–19,21−25] while it was unknown in (32.3%) of the cases. Only two cases had a recurrence.[13, 20] NH can arise from skin adnexal structure if located superficially and from mammary ducts if located deep in location.8 Finck et al.,[1] in their series, described NH arising in deep parenchyma and nipple region with no connection to the overlying skin, as seen in the present case. Histomorphology showed the dual type of cell population. One was a polygonal cell with clear cytoplasm, and the other was cuboidal cells with eosinophilic cytoplasm. These neoplasms rarely show mitosis and necrosis. The lack of cytological atypia and monomorphic appearance helps to distinguish it from ductal carcinoma in situ. However, it is not easy to distinguish it from ductal carcinoma in situ in frozen sections.[16] One of the common differential diagnoses for NH is adenomyoepithelioma, which shows two cell patterns. The tumor cells are immunoreactive to myoepithelial markers like SMA, Muscle-specific actin, P63, and CD10. While tumor cells in clear cell hidradenoma are positive for p63 and negative for muscle actin, CD10, and SMA.[16] Malignant transformation has been noted only in 5% of cases of NH [17] The treatment of choice is surgical excision with clean margins and regular follow-up. [21]
Nodular hidradenoma is a rare benign breast disease with female predominance, which needs to be distinguished from cystic lesion and awareness is must to avoid unnecessary surgical intervention and morbidity.
Funding (information that explains whether and by whom the research was supported) NIL
Conflicts of interest/Competing interests (include appropriate disclosures) Jyotsna Naresh Bharti , Naveen Sharma, Satya Prakash Meena, Taruna Yadav have no conflict of interest.
Ethics approval (include appropriate approvals or waivers) Ethical approval waived by Institutional ethical committee; AIIMS Jodhpur.
Consent to participate (include appropriate statements) NA
Consent for publication (include appropriate statements) Patient has given written consent for publication.
Availability of data and material (data transparency) All data published in manuscript and available in the institute.
Code availability (software application or custom code) NA
Authors' contributions
Jyotsna Naresh Bharti: Manuscript writing /editing /reporting of case /providing of images; Naveen Sharma: Manuscript proofreading/editing; Satya Prakash Meena: Operating Surgeon, concept, literature search; Taruna Yadav: Reporting Radiology.