EXTRAORDINARY CASE REPORT
Solid Carcinoma Revisited: A Possible Variant of Microcystic Adnexal Carcinoma Jonathan H. Lai, MD,* James J. Limacher, MD,†‡ and Robert N. Richards, MD§
Abstract: Primary malignant apocrine and eccrine skin neoplasms are rare and their nosology is still evolving. First described in 1997, solid carcinoma is now considered a discrete entity by some, although this remains controversial. Apocrine differentiation was postulated. A single case since then was the first to include immunohistochemistry findings. The authors report an additional case of solid carcinoma, together with its immunohistochemical profile. A 63-year-old man presented with a firm nodule 3 cm in diameter on the posterior scalp. On punch biopsy, the lesion was interpreted as an adnexal neoplasm of indeterminate malignant potential. The subsequently excised tumor was initially interpreted as microcystic adnexal carcinoma with perineural invasion involving the surgical margins. Re-excision yielded clear surgical margins. After review of all the histologic material, a final diagnosis of solid carcinoma was rendered. Histologically, innumerable solid aggregations of neoplastic epithelial cells filled the dermis and extended into the subcutis. The aggregations varied in size and ranged from round or ovoid nests to elongated columns or cords embedded within a fibrotic stroma. The neoplastic cells were round and uniform in size with small nuclei and pale or clear cytoplasm. Tubular structures and mitoses were absent. Solid carcinoma is a rare skin neoplasm. Histologically, it closely resembles and may be indistinguishable from the solid areas of microcystic adnexal carcinoma. Biologically, solid carcinoma, like microcystic adnexal carcinoma, is an indolent but relentless locally destructive neoplasm that must be removed completely. The clinical, histologic, and biologic similarities suggest that solid carcinoma may be a variant of microcystic adnexal carcinoma. Key Words: solid carcinoma, microcystic adnexal carcinoma, apocrine carcinoma, adnexal neoplasms (Am J Dermatopathol 2014;36:925–927)
INTRODUCTION
Solid carcinoma was first proposed as a discrete entity in 1997 by Requena et al.,1 who postulated it to be of apocrine origin. These authors included in their cases tumors previously reported as “unusual basal cell carcinoma,”2 “sweat From the *Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, and †Department of Medicine, Division of Dermatology, University of Toronto, Toronto, Ontario, Canada; ‡Department of Medicine, LifeLabs, Toronto, Ontario, Canada; and §Department of Medicine (Dermatology), North York General Hospital (Affiliate Hospital of the University of Toronto), Toronto, Ontario, Canada. The authors declare no conflicts of interest. Reprints: Jonathan H. Lai, MD, Division of Anatomical Pathology, Department of Pathology, 5788 University Avenue, Halifax, Nova Scotia, Canada B3H 2Y9 (e-mail: [email protected]). © 2014 Lippincott Williams & Wilkins
Am J Dermatopathol Volume 36, Number 11, November 2014
gland carcinoma of the lips,”3 and “syringomatous carcinoma,”4 all of which they considered as examples of solid carcinoma. Since then, a single additional case report has appeared, the only one that included immunohistochemical findings.5 To the best of our knowledge, the foregoing together comprises the only 15 cases in the literature. We herein report an additional case of this rare entity along with its immunohistochemical profile.
CASE REPORT
A 63-year-old man presented with a firm nodular lesion in the posterior scalp (Fig. 1). A punch biopsy was interpreted as showing a skin adnexal neoplasm of indeterminate malignant potential, with a histologic differential diagnosis including dermal duct tumor, a pale cell variant of basal cell carcinoma, and eccrine (syringoid) carcinoma. The subsequently excised tumor was initially interpreted as a microcystic adnexal carcinoma, extending widely to the surgical margin and exhibiting perineural invasion. Re-excision was performed and yielded clear surgical margins. After review of all the histologic material, a final diagnosis of solid carcinoma was rendered. Histologically, innumerable small solid aggregations of neoplastic epithelial cells extended through the full thickness of the dermis and into the subcutis (Fig. 2). These aggregations varied widely in size and shape and ranged from round or ovoid nests to elongated columns or cords. Deeper aggregations were generally smaller. The stroma was fibrotic, with increased fibrocytes in some areas and dense collagen bundles in others (Fig. 3). The neoplastic cells were round and relatively uniform in size, with small monomorphous nuclei and pale or clear cytoplasm (Fig. 4). Tubular structures and mitoses were rare or absent in the sections. Neoplastic cells were present in a number of nerve fascicles (Fig. 5). In one focus, the tumor was continuous with a follicle and appeared to arise from it (Fig. 6). Immunohistochemical studies showed that the neoplastic cells expressed high–molecular weight keratin (cytokeratin 5), broadspectrum keratin (AE1/AE3), and p63. There was focal immunoreactivity for carcinoembryonic antigen. No immunoreactivity was seen for estrogen receptor, progesterone receptor, BerEp4, epithelial membrane antigen, cytokeratin 7, cytokeratin 20, cytokeratin 18, smooth muscle actin, S-100, CD15, and gross cystic disease fluid protein (GCDFP-15).
DISCUSSION Solid carcinoma is a very rare cutaneous adnexal neoplasm first proposed as a distinct entity by Requena et al.1 and postulated by them to be of apocrine differentiation. This inferred histogenesis was based on the presence, albeit rare, of apocrine decapitation secretion in neoplastic tubules and on the episodic continuity of the neoplasm with follicular infundibula.1 Solid carcinoma is a slow-growing neoplasm with an anatomic distribution similar to microcystic adnexal carcinoma, including a predilection for the nasolabial region and www.amjdermatopathology.com |
925
Lai et al
Am J Dermatopathol Volume 36, Number 11, November 2014
FIGURE 3. Tumor cells with adjacent fibrotic stroma (·200).
FIGURE 1. Clinical lesion was a firm nodule in the posterior scalp.
scalp.1 It is often indurated at presentation because of reticular dermal involvement and usually already involves even deeper structures, such as the subcutis and skeletal muscle.1 Men are more commonly affected than women, and patients are often
FIGURE 2. Whole-mount view showing solid tumor nests infiltrating the dermis and the subcutaneous fat (·7).
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young adults. Clinically, it is a firm nodule or plaque without ulceration and may be misinterpreted as a basal cell carcinoma, a cyst, a lipoma, or morphea.1,5 Histologically, solid carcinoma is reminiscent of the solid component of microcystic adnexal carcinoma. The tumor is composed of innumerable small, solid aggregations of neoplastic epithelial cells usually extending throughout the entire dermis and well into the subcutis—some cases may even involve skeletal muscle. The cellular aggregations vary in size and shape and include nests, columns, cords, and strands, the latter seen especially within the deeper portion of the tumor. In general, the size of the aggregations decreases from the surface to the base of the lesion. Tubule formation is rare, but if present may show hints of apocrine decapitation secretion. The surrounding stroma shows fibroplasia or hyalinization. The lesional cells are cytologically bland and are generally round with small central nuclei. Toward the periphery of the aggregations, the cells may be more columnar. Cells in the center of aggregations tend to have darker cytoplasm, whereas cells in the periphery tend to be pale to clear. Mitotic figures are rare and usually absent. Tumor cells may exhibit a tendency for neurotropism, and focally, the tumor may be continuous with a follicular infundibulum. Clinically and histologically, the morphology of our case conforms well to the foregoing features of solid carcinoma. When Requena et al.1 first described solid carcinoma, they noted that histologically the tumor was identical to the solid component of microcystic adnexal carcinoma. In
FIGURE 4. Cytologically bland tumor cells with pale and clear cytoplasm (·200). 2014 Lippincott Williams & Wilkins
Am J Dermatopathol Volume 36, Number 11, November 2014
FIGURE 5. Tumor cells within and surrounding peripheral nerve (·100).
fact, by definition, the absence or near absence of well-formed tubular or microcystic structures is the only feature differentiating solid carcinoma from microcystic adnexal carcinoma. The 2 entities share a predilection for the same anatomic sites, a bland cytology and an infiltrative growth pattern with prominent stromal desmoplasia, and a propensity for perineural invasion. Mitoses are rare in both. Relative to solid carcinoma, microcystic adnexal carcinoma has more cornifying microcysts in the superficial part of the tumor and more tubular structures in its deeper part. The proportion of solid aggregations of neoplastic cells in microcystic adnexal carcinoma varies but they are always present, especially in the mid and the deeper parts of the tumor. With so few cases in the literature, the biology of solid carcinoma remains incompletely defined. Like microcystic adnexal carcinoma, however, it appears to be a relatively indolent tumor, but one with a potential for relentless local destruction mandating complete removal. To our knowledge, there are no reported deaths attributable to solid carcinoma. The foregoing common factors all suggest a close relationship between solid carcinoma and microcystic adnexal carcinoma. Histogenetic classification of adnexal neoplasms has traditionally focused on the identification of morphologic (including ultrastructural) or immunohistochemical features to provide evidence of origin from or differentiation toward native follicular, sebaceous, apocrine, or eccrine structures.
Solid Carcinoma Revisited
Tubular structures are considered evidence of sweat gland or ductal differentiation. Decapitation secretion is well established as a criterion for apocrine differentiation, but it has no comparable counterpart to identify eccrine differentiation. Association or continuity of a putative sweat gland neoplasm with a follicle and/or a sebaceous gland may be interpreted as evidence of apocrine differentiation on the grounds that embryologically a single germ gives rise to the follicular– sebaceous–apocrine unit, whereas a discrete separate germ gives rise to the eccrine unit. Although the examination of multiple sections may be needed to demonstrate an association with a follicular–sebaceous–apocrine unit, if found (as in our case), we consider it compelling evidence of apocrine differentiation and if not found, either apocrine or eccrine differentiation is possible, particularly because native apocrine and eccrine ducts are histologically indistinguishable except for their origin from separate germs and their respective proximal and distal continuity with different anatomic structures. Finally, cornifying microcystic structures are arguably an expression of differentiation toward follicular infundibular differentation and would thus favor follicular–sebaceous–apocrine histogenesis. Efforts by various investigators to distinguish between apocrine and eccrine differentiation immunohistochemically have been mostly disappointing, and at this time, there is no immunohistochemical gold standard for the identification of either apocrine or eccrine neoplasms. In our case, the immunophenotype was largely noncontributory to the diagnosis. The nosology of cutaneous adnexal neoplasia is notoriously daunting. Literally, dozens of entities have been described, and the terminology continues to evolve. We have reviewed the clinical, histologic, and biologic similarities between solid carcinoma and microcystic carcinoma and cited evidence that at least some of both of these tumors show the features of apocrine differentiation. We propose that, in view of these shared features, solid carcinoma may in fact be a variant of microcystic adnexal carcinoma. Microcystic adnexal carcinoma may represent a morphologic spectrum with a variable proportion of solid and microcystic components, with solid carcinoma positioned toward one end of that spectrum. Until the discovery of truly sensitive and specific histochemical markers or the development of new molecular pathology techniques, the question of apocrine or eccrine origin remains debatable, and the broader term adnexal remains an appropriate descriptor. The more inclusive term solid–microcystic adnexal carcinoma is suggested as a suitable name for the entity. REFERENCES
FIGURE 6. Focally, the tumor is continuous with a follicular infundibulum (·27). 2014 Lippincott Williams & Wilkins
1. Requena L, Kiryu H, Ackerman AB. Neoplasms With Apocrine Differentiation—Ackerman’s Histologic Diagnosis of Neoplastic Skin Disease: A Method by Pattern Analysis. Philadelphia, PA: Lippincott-Raven; 1998. 2. Kelly DE, Klein KM, Harrigan WF. Lip reconstruction following resection for an unusual basal-cell carcinoma. Oral Surg Oral Med Oral Pathol. 1975;40:19–26. 3. Gulmen S, Pullon PA. Sweat gland carcinoma of the lips. Oral Surg Oral Med Oral Pathol. 1976;41:643–649. 4. Abenoza P, Ackerman A. Neoplasms With Eccrine Differentiation— Ackerman’s Histologic Diagnosis of Neoplastic Skin Diseases: A Method by Pattern Analysis. Philadelphia, PA: Lea & Febiger; 1989. 5. Zelger BG, Stelzmueller I, Dunst KM, et al. Solid apocrine carcinoma of the skin: report of a rare adnexal neoplasm mimicking lobular breast carcinoma. J Cutan Pathol. 2008;35:332–336.
www.amjdermatopathology.com |
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Solid Carcinoma Revisited: A Possible Variant of Microcystic Adnexal Carcinoma Jonathan H. Lai, MD,* James J. Limacher, MD,†‡ and Robert N. Richards, MD§
Abstract: Primary malignant apocrine and eccrine skin neoplasms are rare and their nosology is still evolving. First described in 1997, solid carcinoma is now considered a discrete entity by some, although this remains controversial. Apocrine differentiation was postulated. A single case since then was the first to include immunohistochemistry findings. The authors report an additional case of solid carcinoma, together with its immunohistochemical profile. A 63-year-old man presented with a firm nodule 3 cm in diameter on the posterior scalp. On punch biopsy, the lesion was interpreted as an adnexal neoplasm of indeterminate malignant potential. The subsequently excised tumor was initially interpreted as microcystic adnexal carcinoma with perineural invasion involving the surgical margins. Re-excision yielded clear surgical margins. After review of all the histologic material, a final diagnosis of solid carcinoma was rendered. Histologically, innumerable solid aggregations of neoplastic epithelial cells filled the dermis and extended into the subcutis. The aggregations varied in size and ranged from round or ovoid nests to elongated columns or cords embedded within a fibrotic stroma. The neoplastic cells were round and uniform in size with small nuclei and pale or clear cytoplasm. Tubular structures and mitoses were absent. Solid carcinoma is a rare skin neoplasm. Histologically, it closely resembles and may be indistinguishable from the solid areas of microcystic adnexal carcinoma. Biologically, solid carcinoma, like microcystic adnexal carcinoma, is an indolent but relentless locally destructive neoplasm that must be removed completely. The clinical, histologic, and biologic similarities suggest that solid carcinoma may be a variant of microcystic adnexal carcinoma. Key Words: solid carcinoma, microcystic adnexal carcinoma, apocrine carcinoma, adnexal neoplasms (Am J Dermatopathol 2014;36:925–927)
INTRODUCTION
Solid carcinoma was first proposed as a discrete entity in 1997 by Requena et al.,1 who postulated it to be of apocrine origin. These authors included in their cases tumors previously reported as “unusual basal cell carcinoma,”2 “sweat From the *Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, and †Department of Medicine, Division of Dermatology, University of Toronto, Toronto, Ontario, Canada; ‡Department of Medicine, LifeLabs, Toronto, Ontario, Canada; and §Department of Medicine (Dermatology), North York General Hospital (Affiliate Hospital of the University of Toronto), Toronto, Ontario, Canada. The authors declare no conflicts of interest. Reprints: Jonathan H. Lai, MD, Division of Anatomical Pathology, Department of Pathology, 5788 University Avenue, Halifax, Nova Scotia, Canada B3H 2Y9 (e-mail: [email protected]). © 2014 Lippincott Williams & Wilkins
Am J Dermatopathol Volume 36, Number 11, November 2014
gland carcinoma of the lips,”3 and “syringomatous carcinoma,”4 all of which they considered as examples of solid carcinoma. Since then, a single additional case report has appeared, the only one that included immunohistochemical findings.5 To the best of our knowledge, the foregoing together comprises the only 15 cases in the literature. We herein report an additional case of this rare entity along with its immunohistochemical profile.
CASE REPORT
A 63-year-old man presented with a firm nodular lesion in the posterior scalp (Fig. 1). A punch biopsy was interpreted as showing a skin adnexal neoplasm of indeterminate malignant potential, with a histologic differential diagnosis including dermal duct tumor, a pale cell variant of basal cell carcinoma, and eccrine (syringoid) carcinoma. The subsequently excised tumor was initially interpreted as a microcystic adnexal carcinoma, extending widely to the surgical margin and exhibiting perineural invasion. Re-excision was performed and yielded clear surgical margins. After review of all the histologic material, a final diagnosis of solid carcinoma was rendered. Histologically, innumerable small solid aggregations of neoplastic epithelial cells extended through the full thickness of the dermis and into the subcutis (Fig. 2). These aggregations varied widely in size and shape and ranged from round or ovoid nests to elongated columns or cords. Deeper aggregations were generally smaller. The stroma was fibrotic, with increased fibrocytes in some areas and dense collagen bundles in others (Fig. 3). The neoplastic cells were round and relatively uniform in size, with small monomorphous nuclei and pale or clear cytoplasm (Fig. 4). Tubular structures and mitoses were rare or absent in the sections. Neoplastic cells were present in a number of nerve fascicles (Fig. 5). In one focus, the tumor was continuous with a follicle and appeared to arise from it (Fig. 6). Immunohistochemical studies showed that the neoplastic cells expressed high–molecular weight keratin (cytokeratin 5), broadspectrum keratin (AE1/AE3), and p63. There was focal immunoreactivity for carcinoembryonic antigen. No immunoreactivity was seen for estrogen receptor, progesterone receptor, BerEp4, epithelial membrane antigen, cytokeratin 7, cytokeratin 20, cytokeratin 18, smooth muscle actin, S-100, CD15, and gross cystic disease fluid protein (GCDFP-15).
DISCUSSION Solid carcinoma is a very rare cutaneous adnexal neoplasm first proposed as a distinct entity by Requena et al.1 and postulated by them to be of apocrine differentiation. This inferred histogenesis was based on the presence, albeit rare, of apocrine decapitation secretion in neoplastic tubules and on the episodic continuity of the neoplasm with follicular infundibula.1 Solid carcinoma is a slow-growing neoplasm with an anatomic distribution similar to microcystic adnexal carcinoma, including a predilection for the nasolabial region and www.amjdermatopathology.com |
925
Lai et al
Am J Dermatopathol Volume 36, Number 11, November 2014
FIGURE 3. Tumor cells with adjacent fibrotic stroma (·200).
FIGURE 1. Clinical lesion was a firm nodule in the posterior scalp.
scalp.1 It is often indurated at presentation because of reticular dermal involvement and usually already involves even deeper structures, such as the subcutis and skeletal muscle.1 Men are more commonly affected than women, and patients are often
FIGURE 2. Whole-mount view showing solid tumor nests infiltrating the dermis and the subcutaneous fat (·7).
926
| www.amjdermatopathology.com
young adults. Clinically, it is a firm nodule or plaque without ulceration and may be misinterpreted as a basal cell carcinoma, a cyst, a lipoma, or morphea.1,5 Histologically, solid carcinoma is reminiscent of the solid component of microcystic adnexal carcinoma. The tumor is composed of innumerable small, solid aggregations of neoplastic epithelial cells usually extending throughout the entire dermis and well into the subcutis—some cases may even involve skeletal muscle. The cellular aggregations vary in size and shape and include nests, columns, cords, and strands, the latter seen especially within the deeper portion of the tumor. In general, the size of the aggregations decreases from the surface to the base of the lesion. Tubule formation is rare, but if present may show hints of apocrine decapitation secretion. The surrounding stroma shows fibroplasia or hyalinization. The lesional cells are cytologically bland and are generally round with small central nuclei. Toward the periphery of the aggregations, the cells may be more columnar. Cells in the center of aggregations tend to have darker cytoplasm, whereas cells in the periphery tend to be pale to clear. Mitotic figures are rare and usually absent. Tumor cells may exhibit a tendency for neurotropism, and focally, the tumor may be continuous with a follicular infundibulum. Clinically and histologically, the morphology of our case conforms well to the foregoing features of solid carcinoma. When Requena et al.1 first described solid carcinoma, they noted that histologically the tumor was identical to the solid component of microcystic adnexal carcinoma. In
FIGURE 4. Cytologically bland tumor cells with pale and clear cytoplasm (·200). 2014 Lippincott Williams & Wilkins
Am J Dermatopathol Volume 36, Number 11, November 2014
FIGURE 5. Tumor cells within and surrounding peripheral nerve (·100).
fact, by definition, the absence or near absence of well-formed tubular or microcystic structures is the only feature differentiating solid carcinoma from microcystic adnexal carcinoma. The 2 entities share a predilection for the same anatomic sites, a bland cytology and an infiltrative growth pattern with prominent stromal desmoplasia, and a propensity for perineural invasion. Mitoses are rare in both. Relative to solid carcinoma, microcystic adnexal carcinoma has more cornifying microcysts in the superficial part of the tumor and more tubular structures in its deeper part. The proportion of solid aggregations of neoplastic cells in microcystic adnexal carcinoma varies but they are always present, especially in the mid and the deeper parts of the tumor. With so few cases in the literature, the biology of solid carcinoma remains incompletely defined. Like microcystic adnexal carcinoma, however, it appears to be a relatively indolent tumor, but one with a potential for relentless local destruction mandating complete removal. To our knowledge, there are no reported deaths attributable to solid carcinoma. The foregoing common factors all suggest a close relationship between solid carcinoma and microcystic adnexal carcinoma. Histogenetic classification of adnexal neoplasms has traditionally focused on the identification of morphologic (including ultrastructural) or immunohistochemical features to provide evidence of origin from or differentiation toward native follicular, sebaceous, apocrine, or eccrine structures.
Solid Carcinoma Revisited
Tubular structures are considered evidence of sweat gland or ductal differentiation. Decapitation secretion is well established as a criterion for apocrine differentiation, but it has no comparable counterpart to identify eccrine differentiation. Association or continuity of a putative sweat gland neoplasm with a follicle and/or a sebaceous gland may be interpreted as evidence of apocrine differentiation on the grounds that embryologically a single germ gives rise to the follicular– sebaceous–apocrine unit, whereas a discrete separate germ gives rise to the eccrine unit. Although the examination of multiple sections may be needed to demonstrate an association with a follicular–sebaceous–apocrine unit, if found (as in our case), we consider it compelling evidence of apocrine differentiation and if not found, either apocrine or eccrine differentiation is possible, particularly because native apocrine and eccrine ducts are histologically indistinguishable except for their origin from separate germs and their respective proximal and distal continuity with different anatomic structures. Finally, cornifying microcystic structures are arguably an expression of differentiation toward follicular infundibular differentation and would thus favor follicular–sebaceous–apocrine histogenesis. Efforts by various investigators to distinguish between apocrine and eccrine differentiation immunohistochemically have been mostly disappointing, and at this time, there is no immunohistochemical gold standard for the identification of either apocrine or eccrine neoplasms. In our case, the immunophenotype was largely noncontributory to the diagnosis. The nosology of cutaneous adnexal neoplasia is notoriously daunting. Literally, dozens of entities have been described, and the terminology continues to evolve. We have reviewed the clinical, histologic, and biologic similarities between solid carcinoma and microcystic carcinoma and cited evidence that at least some of both of these tumors show the features of apocrine differentiation. We propose that, in view of these shared features, solid carcinoma may in fact be a variant of microcystic adnexal carcinoma. Microcystic adnexal carcinoma may represent a morphologic spectrum with a variable proportion of solid and microcystic components, with solid carcinoma positioned toward one end of that spectrum. Until the discovery of truly sensitive and specific histochemical markers or the development of new molecular pathology techniques, the question of apocrine or eccrine origin remains debatable, and the broader term adnexal remains an appropriate descriptor. The more inclusive term solid–microcystic adnexal carcinoma is suggested as a suitable name for the entity. REFERENCES
FIGURE 6. Focally, the tumor is continuous with a follicular infundibulum (·27). 2014 Lippincott Williams & Wilkins
1. Requena L, Kiryu H, Ackerman AB. Neoplasms With Apocrine Differentiation—Ackerman’s Histologic Diagnosis of Neoplastic Skin Disease: A Method by Pattern Analysis. Philadelphia, PA: Lippincott-Raven; 1998. 2. Kelly DE, Klein KM, Harrigan WF. Lip reconstruction following resection for an unusual basal-cell carcinoma. Oral Surg Oral Med Oral Pathol. 1975;40:19–26. 3. Gulmen S, Pullon PA. Sweat gland carcinoma of the lips. Oral Surg Oral Med Oral Pathol. 1976;41:643–649. 4. Abenoza P, Ackerman A. Neoplasms With Eccrine Differentiation— Ackerman’s Histologic Diagnosis of Neoplastic Skin Diseases: A Method by Pattern Analysis. Philadelphia, PA: Lea & Febiger; 1989. 5. Zelger BG, Stelzmueller I, Dunst KM, et al. Solid apocrine carcinoma of the skin: report of a rare adnexal neoplasm mimicking lobular breast carcinoma. J Cutan Pathol. 2008;35:332–336.
www.amjdermatopathology.com |
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