Papillomatosis of breasts
| Papillomatosis of the breast | |
|---|---|
| Other names | Juvenile papillomatosis, Swiss cheese disease |
| Specialty | Breast surgery, Surgical oncology |
| Usual onset | Children, adolescents, adult men and women |
| Treatment | Surgical removal |
| Prognosis | guarded |
| Frequency | rare |
| Deaths | rare |
Papillomatosis of the breast (PB) is a rare, benign, epitheliosis-like lesion, i.e. an overgrowth of the cells lining the ducts of glands that resembles a papilla (i.e. small rounded protuberance) or nipple-like nodule/tumor. PB tumors develop in the apocrine glands of the breast.[1][2] PB is also termed juvenile papillomatosis because of its frequent occurrence in younger women (including, in uncommon cases, children and adolescent females) and Swiss cheese disease because of its microscopic appearance.[3] Rarely, PB has also been diagnosed in very young, adolescent, and adult males.[4]
A PB tumor is typically an asymptomatic lesion that is detected on examination as a palpable but otherwise symptomless breast mass or in some cases by routine breast cancer screening methods in individuals unaware of the mass's presence.[3] Although PB tumors are themselves benign, a significant percentage of individuals with these tumors concurrently have or will develop certain types of breast carcinomas and/or have a family history of relatives with breast carcinomas.[5] Cases of PB have also been reported to occur in individuals with a family history of certain genetic diseases.[4]
Pediatric cases of PB tumors are commonly treated by total resection.[6] Complete excision of PB tumors with clear surgical margins to remove all tumor cells is important in order to reduce a recurrence of the tumor at its site of removal.[3][7][8] Regular, long-term follow-up monitoring is recommended especially for individuals with multiple PB tumors, individuals who have a family history of relatives with breast cancer, and/or individuals with PB tumors that have other aggressive features.[7][8]
Presentation
The majority of BP cases have been diagnosed in Caucasians with only rare cases being diagnosed in individuals of Asian,[9] or African[10] descent. At least 6 cases of BP have been reported to occur in women during their pregnancies.[11] BP tumors commonly present as multinodular, mobile, well-circumscribed masses 3 to 8 centimeters in widest diameter located in the periphery of a breast.[7] Rarely, these tumors have been less than 3 centimeters in widest diameter or larger than 8 centimeters in widest diameter; in one case, the PB tumor, termed giant juvenile papillomatosis, was 20 centimeters in widest diameter.[8] While usually a single tumor, BP tumors have presented as two or more tumors in one breast[7][12] or bilateral disease, i.e. tumors in both breasts.[10][13] In a review of 354 reported cases of PB: 344 occurred in females (~96%), 6 in males (~2%), and 2 (~0.6) in individuals whose sex was not mentioned; the individuals ranged from 7 months to 81 years (average age 26 years); 316 (~90%) individuals complained of a palpable mass, 2 (~0.6%) of pain, 2 (~0.6%) of nipple discharge (this discharge may be bloody[14]), and 1 (0.3%) of a palpable mass plus nipple discharge; 18 (~5%) had an entirely symptomless breast tumor detected by breast cancer screening methods; 25 (~7%) individuals had an associated breast carcinoma at diagnoses and 68 (19%) had a family history of breast cancer.[3] The breast cancers associated with BP are mammary secretory carcinomas, lobular carcinoma in situ, invasive lobular carcinoma, ductal carcinoma in situ, and invasive ductal carcinoma.[4][5][14] A positive family history of breast cancer together with recurrent bilateral PG is a risk factor for developing these breast cancers.[4] The genetic diseases associated with BP are Cowden disease, Noonan syndrome, Proteus syndrome, and neurofibromatosis type 1.[14]
Pathology
At their surgical excision, PB lesions grossly appear as tumors with visible cysts of different sizes intermingled with fibrotic areas. Some of these cysts are filled with liquid.[3] The microscopic histopathological findings in PB tumor tissues stained with H&E include the excessive proliferation of irregularly shaped, variably sized, ductal epithelial cells, ductal myoepithelial cells,[3][4] and lipid-laden, foamy intra-cystic histiocytes[5] within the breast's apocrine glands, abnormally widened gland ducts, abundant large extracellular and intracellular cysts (many of which are filled with mucus[3]) that give the lesions their Swiss cheese-like appearance, and sclerosing adenosis (i.e. enlarged breast lobules distorted by scar-like tissue).[11] The lesions may contain areas of microcalcification[5] and/or necrosis, i.e. dead cells.[5][8] Immunohistochemical analyses of these tumors may detect cells that express estrogen,[4] progesterone, epidermal growth factor and/or HER2/neu receptors.[8]
Gene abnormalities
In a study of 10 individuals with PB, 5 had tumor cells with mutations in the PIK3CA gene and 2 had tumor cells with mutations in the AKT1 gene. The mutations occurred in these genes' hot spots, i.e. areas of a genes' DNA that are likely to mutate. Two of the 3 individuals with family histories of breast cancer had PIK3C gene mutation and one individual with a family history of breast cancer had an AKT1 gene mutation.[3] A subsequent study found PIK3CA gene mutations in 3 of 3 individuals with PB. One of these individuals had PB coexisting with ductal carcinoma in situ and invasive ductal carcinoma; the same PIC3K mutation was detected in all three lesions.[5] The PIK3CA and AKT1 genes are key components of the PI3K/AKT/mTOR pathway of cell signaling. This pathway promotes cell growth, proliferation, survival, and the development and/or progression of various cancers including breast carcinomas.[3] It is interesting to note that individuals with two genetic diseases associated with the development of PB have gene mutations involving this pathway, i.e. the Proteus syndrome caused by an activating mutations in the AKT1 gene and the Cowden syndrome caused by a mutation in the PTEN (gene) tumor suppressor gene.[5] Finally, individual cases of PB have been found to have mutations in the MET, FGFR3, PTEN, ATM, GNAS and/or a gene, NF1, which causes another genetic disease associated with PB, neurofibromatosis type 1.[3] Further studies are needed to determine the role these mutations may play in the development of PB and/or their potential usefulness in predicting the development of breast carcinomas in individuals with PB.[3][5]
Diagnosis
PB tumors are diagnosed based on their microscopic histopathology,[13] including in particular the presence of cysts that give these tumors their Swiss cheese appearance.[11] PB tumors have clinical manifestations which are very similar to, and prior to tissue analysis have been diagnoses as, fibroadenomas. However, the two breast tumor types have very different microscopic features.[9] Studies have found that ultrasonography, including Doppler ultrasonography, help in diagnosing PB, particularly in pregnant women where other imaging methods such as mammography and magnetic resonance imaging expose the mother and her fetus to radiation.[3][11][13] Ultrasonography imaging typically reveals a poorly-defined heterogeneous mass with various small, round, echo-free areas mostly located near the lesions' borders and thereby helps in distinguishing PB tumors from similar cystic lesions such as fibroadenomas, phyllodes tumors, papillomas growing within a cyst, and breast cancer.[9] The diagnosis of PB may be suggested in individuals with the clinical presentation of PB plus the presence of a family history of mammary secretory carcinomas, lobular carcinoma, ductal carcinoma in situ, invasive ductal carcinomas of no special type,[4][5][14] Cowden disease, Noonan syndrome, Proteus syndrome, or neurofibromatosis type 1.[14]
Treatment
The preferred treatment for PB tumors is complete surgical excision with histologic confirmation that all tumor tissue has been removed: incomplete excision of this tumor's tissues commonly leads to recurrence of the tumor at the site of its surgical removal.[13][15] PB tumors diagnosed in pregnant females during their late third trimester, it is suggested, may have their surgical excision of the tumor postponed until after delivery.[11] Annual clinical follow-ups, including physical examination and/or ultrasonography of the breasts is recommended for individuals with PB and their female relatives, particularly for individuals with a family history of breast cancer, recurrent PB tumors, and/or bilateral PB tumors.[7][9][13] Because excision can cause permanent deformity or dysfunction of the breast tissue, some studies recommend that surgical intervention in children should be reserved for symptomatic tumors or tumors that are associated with a compromised prognosis[14] and that any resections done in children should aim to preserve as much normal breast tissue as possible.[6]
Prognosis
While removal of all PB tumor tissues generally indicates that no further treatment is indicated, the possibility that the carcinomas associated with this disease may occur soon or long after the original PB tumor is removed and may be less effectively treated than PB tumors make the prognosis of PB somewhat guarded.[13]
References
- ^ Ambrosi F, Rossi ED, Calderoni S, Cucchi MC, Saguatti G, Foschini MP (February 2020). "Infiltrating Epitheliosis of the Breast: Fine Needle Aspiration Cytology". International Journal of Surgical Pathology. 28 (1): 38–43. doi:10.1177/1066896919863488. PMID 31328594. S2CID 198135661.
- ^ MD, Juan P. Palazzo (2011). Difficult Diagnoses in Breast Pathology. Demos Medical Publishing. ISBN 9781935281306. Retrieved 21 June 2018.
- ^ a b c d e f g h i j k l Guillet C, Rechsteiner M, Bellini E, Choschzick M, Moskovszky L, Dedes K, Papassotiropoulos B, Varga Z (April 2020). "Juvenile papillomatosis of the breast (Swiss cheese disease) has frequent associations with PIK3CA and/or AKT1 mutations". Human Pathology. 98: 64–73. doi:10.1016/j.humpath.2020.02.002. PMID 32088208. S2CID 211261338.
- ^ a b c d e f g Viswanathan K, McMillen B, Cheng E, D'Alfonso T, Patel A, Hoda SA (September 2017). "Juvenile Papillomatosis (Swiss-Cheese Disease) of Breast in an Adult Male With Sequential Diagnoses of Ipsilateral Intraductal, Invasive, and Widely Metastatic Carcinoma: A Case Report and Review of the Disease in Males". International Journal of Surgical Pathology. 25 (6): 536–542. doi:10.1177/1066896917705198. PMID 28420303. S2CID 13659623.
- ^ a b c d e f g h i D'Alfonso TM, Pareja F, Da Cruz Paula A, Vahdatinia M, Gazzo A, Ferrando L, da Silva EM, Cheng E, Sclafani L, Chandarlapaty S, Zhang H, Hoda SA, Wen HY, Brogi E, Weigelt B, Reis-Filho JS (March 2021). "Whole-exome sequencing analysis of juvenile papillomatosis and coexisting breast carcinoma". Journal of Pathology: Clinical Research. 7 (2): 113–120. doi:10.1002/cjp2.190. PMC 7869928. PMID 33263939.
- ^ a b De Silva NK, Brandt ML (December 2006). "Disorders of the breast in children and adolescents, Part 2: breast masses". Journal of Pediatric and Adolescent Gynecology. 19 (6): 415–8. doi:10.1016/j.jpag.2006.09.002. PMID 17174833.
- ^ a b c d e Knaus ME, Grabowksi JE (August 2021). "Pediatric Breast Masses: An Overview of the Subtypes, Workup, Imaging, and Management". Advances in Pediatrics. 68: 195–209. doi:10.1016/j.yapd.2021.05.006. PMID 34243852. S2CID 235786044.
- ^ a b c d e Olarinoye-Akorede SA, Farouk B, Liman AA, Kajogbola GA (December 2018). "Giant juvenile papillomatosis of the breast in a Nigerian girl". BMJ Case Reports. 11 (1): e225993. doi:10.1136/bcr-2018-225993. PMC 6301522. PMID 30567257.
- ^ a b c d Wang T, Li YQ, Liu H, Fu XL, Tang SC (December 2014). "Bifocal juvenile papillomatosis as a marker of breast cancer: A case report and review of the literature". Oncology Letters. 8 (6): 2587–2590. doi:10.3892/ol.2014.2600. PMC 4214435. PMID 25364432.
- ^ a b El-Saify WM (2007). "Florid papillomatosis: A rare cause of bilateral giant breast lumps in the elderly". The Breast Journal. 13 (1): 95–7. doi:10.1111/j.1524-4741.2006.00373.x. PMID 17214804. S2CID 6651965.
- ^ a b c d e Beyer I, Mutschler N, Blum KS, Mohrmann S (July 2015). "Breast Lesions during Pregnancy - a Diagnostic Challenge: Case Report". Breast Care (Basel, Switzerland). 10 (3): 207–10. doi:10.1159/000381823. PMC 4569211. PMID 26557826.
- ^ Nio Y, Minari Y, Hirahara N, Takamura M, Sasaki S, Iguchi C, Tamura K (April 1998). "A Case of Multiple Juvenile Papillomatosis of the Breast and Its Immunohistochemical Pathology". Breast Cancer (Tokyo, Japan). 5 (2): 187–193. doi:10.1007/BF02966694. PMID 11091647. S2CID 44616354.
- ^ a b c d e f Lad S, Seely J, Elmaadawi M, Peddle S, Perkins G, Robertson S, Ibach K, Haggar F, Arnaout A (October 2014). "Juvenile papillomatosis: a case report and literature review". Clinical Breast Cancer. 14 (5): e103–5. doi:10.1016/j.clbc.2014.03.003. PMID 24997851.
- ^ a b c d e f Tourlamain G, Quaegebeur K, Dedeurwaerde F, Logghe K (December 2020). "Juvenile Papillomatosis in a Young Child: A Case of Infantile Bloody Nipple Discharge". Journal of Pediatric and Adolescent Gynecology. 33 (6): 720–722. doi:10.1016/j.jpag.2020.07.009. PMID 32717364. S2CID 220841191.
- ^ Wang T, Li YQ, Liu H, Fu XL, Tang SC (December 2014). "Bifocal juvenile papillomatosis as a marker of breast cancer: A case report and review of the literature". Oncology Letters. 8 (6): 2587–2590. doi:10.3892/ol.2014.2600. PMC 4214435. PMID 25364432.